Medscape Medical News
Antibiotics for H pylori May Prevent Gastric Cancer
Beth Skwarecki
July 24, 2015
Eliminating the bacterium Helicobacter pylori can reduce the risk for gastric cancer in healthy individuals, according to a systematic review of six trials published online July 22 in the Cochrane Database of Systematic Reviews. The five positive trials were done in Asian populations, and the authors caution that "we cannot necessarily extrapolate this data to other populations."
Therapy to eradicate H pylori, a known cause of peptic ulcers, consists of a 1- to 2-week course of antibiotics either alone or in combination with acid suppressant therapy, bismuth, or both.
For the current review, the investigators considered randomized controlled trials that compared eradication with placebo or with no treatment. The trials included 6497 healthy, asymptomatic adults who tested positive for the presence of the bacterium. Gastric cancer was defined as any gastric adenocarcinoma, including intestinal (differentiated) or diffuse (undifferentiated) type or without specified histology.
In the antibiotic-treatment group, the incidence of gastric cancer was 51 of 3294 people compared with 76 of 3203, a risk ratio of 0.66 (95% confidence interval [CI], 0.46 - 0.95), based on moderate-quality evidence.
Only one trial reported on esophageal cancer, with two cases out of 817 patients in the treatment group compared with one in the placebo group (risk ratio [RR], 1.99; 95% CI, 0.18 - 21.91). None of the trials reported other adverse events, leading the review authors to write that "we were unable to assess the balance of benefits and harms if population screening and treatment for H. pylori infection were to be adopted as a public health measure."
The risk for death from all causes did not differ between groups (RR 1.09; 95% CI 0.86 to 1.38), and the authors could not asses the mortality risk from gastric cancer because of the wide confidence intervals (RR, 0.67; 95% CI, 0.40 - 1.11).
"The review highlights the need for further trials in different populations to provide more evidence, and these should report both the benefits and harms of such an approach," lead author Alexander Ford, MBChB, MD, from St. James's University Hospital and Leeds University in the United Kingdom, said in a journal news release.
The authors have disclosed no relevant financial relationships.
Cochrane Database Syst Rev. Published online July 22, 2015. Abstract
viernes, 31 de julio de 2015
High Risk for Gastric Cancer in Patients With Gastric Lesions
Medscape Medical News > Oncology
High Risk for Gastric Cancer in Patients With Gastric Lesions
Liam Davenport
July 30, 2015
Patients with precancerous gastric lesions face an increased risk of developing gastric cancer that increases dramatically with increasing severity of the lesion, say Swedish scientists. The findings underscore the importance of patient surveillance, they add.
The study was published online July 27 in the BMJ.
Patients with minor changes in intestinal mucosa had a 1.8-fold risk of developing gastric cancer during the next 20 years vs those with healthy tissue. The risk rose to almost 11-fold risk in patients with dysplasia.
The findings confirm the validity of Correa's cascade, a widely accepted pathologic progression to gastric cancer that is thought to be initiated by Helicobacter pylori infection, say the authors. The cascade leads from normal mucosa to dysplasia via minor mucosal change, gastritis, atrophic gastritis, and intestinal metaplasia.
"Our results in a low risk Western patient population show that all stages of Correa's cascade predict an incidence of gastric cancer above that of the general population," they note.
Study Details
To determine the incidence of gastric cancer among patients with gastric precancerous lesions, the researchers conducted a population-based cohort study using data on 405,211 patients from Swedish national registers who had undergone gastric biopsies between 1979 and 2011.
Excluding the first 2 years of follow-up, the team identified 1599 cases of gastric cancer diagnosed during an average follow-up period of approximately 10 years.
They calculated that the annual crude incidence of gastric cancer was 20 x 10−5 for those in the normal mucosa group, 42 x 10−5 for patients with minor changes, 59 x 10−5 for those with gastritis, 100 x 10−5 for patients with atrophic gastritis, 129 x 10−5 for the intestinal metaplasia group, and 263 x 10−5 for those with dysplasia.
This translated into standardized incidence ratios compared with the general Swedish population of 1.0, 1.5, 1.8, 2.8, 3.4, and 6.5, respectively.
It was determined that the 20-year risk of developing gastric cancer was approximately as follows:
1 in 256 for patients with a normal mucosa;
1 in 85 for those with gastritis;
1 in 50 for patients with atrophic gastritis;
1 in 39 for those with intestinal metaplasia; and
1 in 19 for dysplasia.
On Cox regression analysis, the risk for gastric cancer increased monotonically with progression along Correa's cascade, ranging from a hazard ratio compared with normal mucosa of 1.8 for minor mucosal change to 10.9 for dysplasia.
Highlights Need for Surveillance
Senior author Weimin Ye, MD, PhD, Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden, discussed the findings with Medscape Medical News.
He described the study as a "first step" in characterizing the risks faced by patients with gastric precancerous lesions, but one that nevertheless confirms the validity of Correa's cascade.
Although more work, including cost-benefit analyses, would be needed to develop surveillance strategies from the results, Dr Ye believes the results the importance of closely following patients with more severe lesions.
"The problem is...[that] clinical guidelines already recommend that even atrophic gastritis patients be followed up every year or every 2 years, [but] very few [doctors] really follow this," he said.
Although noting that the decision is often taken out of doctors' hands, owing to the limitations of their healthcare system, he added: "I think this study reemphasizes that this is really important, but the problem here is also that I think we need more risk markers to try to further stratify patients."
For Dr We and colleagues, the next steps will be to incorporate such markers alongside precancerous lesion stage to develop a more complete picture of a patient's likelihood of developing gastric cancer.
One such marker involves use of genome analysis to determine the H pylori subtype with which a patient is infected, and another involves tumor mutation profiling.
Dr We concluded: "The other way is a more traditional approach, for example, family history, smoking, something like that.... But I think the most important thing is first two approaches."
This study was supported by the Swedish Research Council and Cancerfonden. Coauthor Huan Song was partly supported by a scholarship from the China Scholarship Council. Coauthor Isabella Guncha Ekheden is partly supported by a scholarship from the Karolinska Institutet MD/PhD programme. The funders had no role in the conduct of this research. The other authors have disclosed no relevant financial relationships.
BMJ. Published online July 27, 2015. Abstract
martes, 28 de julio de 2015
Radium-223 and Prostate Cancer
Researchers Continue to Explore Optimal Use of Radium-223
Published Online: Tuesday, June 30, 2015
Tanya B. Dorff, MD
Tanya B. Dorff, MD
Limited data exist regarding optimal patient selection and sequencing of radium-223 relative to other approved treatments for patients with metastatic castration-resistant prostate cancer (mCRPC).1 In a presentation given at the 2015 ASCO Annual Meeting, Tanya B. Dorff, MD, Keck School of Medicine of USC, discussed the available research on the radiopharmaceutical agent.
Patient Selection
Radium-223 was approved in 2013 for the treatment of patients with metastatic CRPC and bone metastases,1 based on data from the phase III ALSYMPCA trial in patients with metastatic CRPC who received radium-223.2
The ALSYMPCA trial randomized 928 men with bone pain from metastatic CRPC who had either progressed on docetaxel or who were not candidates for docetaxel, to radium-223 or placebo (each given monthly for 6 total doses) plus standard care.2
Data reported at an interim analysis showed a median overall survival of 14 months versus 11.2 months with radium-223 versus placebo, respectively (HR = 0.70; P = .00185). The time to the first skeletal-related event was a median of 15.6 months in the radium-223 arm compared with 9.8 months with placebo (HR = 0.658; P = .00037).
There was no clear distinction regarding radium-223 benefit according to the extent of disease (as defined by the number of bone lesions). Subgroup analyses did not provide definitive information on which patients may benefit, as the numbers of patients were small.2 There was no difference in median time to PSA progression between the radium-223 and placebo arms.2
These results confirm the need for further studies to define patient groups most likely to benefit from radium-223 treatment. “I would contend that there is really no clinical marker as of now that can help us to say, ‘This is a patient who shouldn’t get radium or who wouldn’t benefit.’ There is limited utility in these subgroup analyses,” concluded Dorff.
Sequencing
Determining the treatment sequence of radium-223 relative to other therapies is challenging for clinicians. Because of the potential for additive myelosuppression from radiopharmaceuticals and cytotoxic chemotherapy, most studies have focused on the timing of radium-223 either before or after docetaxel-based chemotherapy.1 Retrospective analysis from ALSYMPCA found somewhat higher rates of hematologic toxicity and packed red blood cell transfusions in patients receiving radium-223 who previously received docetaxel compared with those who did not.3
“But you will see that the grade 3 and 4 numbers remain relatively low, and I would argue that there’s nothing here that tells me it’s not safe to use this. So you can really choose to use this before or after docetaxel,” said Dorff.
“Similarly, when you look at transfusions, there are more transfusions, but you will see that they are for both the radium and the placebo group in the docetaxel pretreated cohort, suggesting that maybe some of this is related to disease burden…but again, I don’t think this is prohibitive in terms of choosing to use this before or after docetaxel,” she continued.
In addition, subgroup analysis of ALSYMPCA revealed that, although symptomatic skeletal events were not delayed in docetaxel-naïve patients, there was a substantial delay in these events in patients who were pretreated with docetaxel. “This gets back to that concept that maybe earlier on, patients are just not at as much risk, so they will stand perhaps greater benefit to using radium-223 later, after docetaxel,” commented Dorff.
The number of included patients was small; however, cautious interpretation suggests that docetaxel-pretreated patients may represent a group in which bone-targeting therapy may produce a greater effect.1
“Speaking to that, they found that there were actually about 5 fewer hospital days per patient per year in the docetaxel-naïve cohort that was treated with radium compared to placebo, and about 8 fewer hospital days per patient per year for docetaxel-pretreated patients treated with radium-223, suggesting that there is really a palliative benefit here,” Dorff noted.
“In patients who have received radium-223, they may require less palliative external beam radiotherapy down the road…if you are faced with a patient who is in pain, it might be reasonable to try the radium-223 first, and then if they are not experiencing pain palliation add the external beam radiation, but some patients may end up not needing it.”
- See more at: http://www.onclive.com/web-exclusives/researchers-continue-to-explore-optimal-use-of-radium-223#sthash.2kECv9n6.dpuf
Published Online: Tuesday, June 30, 2015
Tanya B. Dorff, MD
Tanya B. Dorff, MD
Limited data exist regarding optimal patient selection and sequencing of radium-223 relative to other approved treatments for patients with metastatic castration-resistant prostate cancer (mCRPC).1 In a presentation given at the 2015 ASCO Annual Meeting, Tanya B. Dorff, MD, Keck School of Medicine of USC, discussed the available research on the radiopharmaceutical agent.
Patient Selection
Radium-223 was approved in 2013 for the treatment of patients with metastatic CRPC and bone metastases,1 based on data from the phase III ALSYMPCA trial in patients with metastatic CRPC who received radium-223.2
The ALSYMPCA trial randomized 928 men with bone pain from metastatic CRPC who had either progressed on docetaxel or who were not candidates for docetaxel, to radium-223 or placebo (each given monthly for 6 total doses) plus standard care.2
Data reported at an interim analysis showed a median overall survival of 14 months versus 11.2 months with radium-223 versus placebo, respectively (HR = 0.70; P = .00185). The time to the first skeletal-related event was a median of 15.6 months in the radium-223 arm compared with 9.8 months with placebo (HR = 0.658; P = .00037).
There was no clear distinction regarding radium-223 benefit according to the extent of disease (as defined by the number of bone lesions). Subgroup analyses did not provide definitive information on which patients may benefit, as the numbers of patients were small.2 There was no difference in median time to PSA progression between the radium-223 and placebo arms.2
These results confirm the need for further studies to define patient groups most likely to benefit from radium-223 treatment. “I would contend that there is really no clinical marker as of now that can help us to say, ‘This is a patient who shouldn’t get radium or who wouldn’t benefit.’ There is limited utility in these subgroup analyses,” concluded Dorff.
Sequencing
Determining the treatment sequence of radium-223 relative to other therapies is challenging for clinicians. Because of the potential for additive myelosuppression from radiopharmaceuticals and cytotoxic chemotherapy, most studies have focused on the timing of radium-223 either before or after docetaxel-based chemotherapy.1 Retrospective analysis from ALSYMPCA found somewhat higher rates of hematologic toxicity and packed red blood cell transfusions in patients receiving radium-223 who previously received docetaxel compared with those who did not.3
“But you will see that the grade 3 and 4 numbers remain relatively low, and I would argue that there’s nothing here that tells me it’s not safe to use this. So you can really choose to use this before or after docetaxel,” said Dorff.
“Similarly, when you look at transfusions, there are more transfusions, but you will see that they are for both the radium and the placebo group in the docetaxel pretreated cohort, suggesting that maybe some of this is related to disease burden…but again, I don’t think this is prohibitive in terms of choosing to use this before or after docetaxel,” she continued.
In addition, subgroup analysis of ALSYMPCA revealed that, although symptomatic skeletal events were not delayed in docetaxel-naïve patients, there was a substantial delay in these events in patients who were pretreated with docetaxel. “This gets back to that concept that maybe earlier on, patients are just not at as much risk, so they will stand perhaps greater benefit to using radium-223 later, after docetaxel,” commented Dorff.
The number of included patients was small; however, cautious interpretation suggests that docetaxel-pretreated patients may represent a group in which bone-targeting therapy may produce a greater effect.1
“Speaking to that, they found that there were actually about 5 fewer hospital days per patient per year in the docetaxel-naïve cohort that was treated with radium compared to placebo, and about 8 fewer hospital days per patient per year for docetaxel-pretreated patients treated with radium-223, suggesting that there is really a palliative benefit here,” Dorff noted.
“In patients who have received radium-223, they may require less palliative external beam radiotherapy down the road…if you are faced with a patient who is in pain, it might be reasonable to try the radium-223 first, and then if they are not experiencing pain palliation add the external beam radiation, but some patients may end up not needing it.”
- See more at: http://www.onclive.com/web-exclusives/researchers-continue-to-explore-optimal-use-of-radium-223#sthash.2kECv9n6.dpuf
Safety Profile of HPV Vaccines
EMA to Further Clarify Safety Profile of HPV Vaccines
The review will focus on rare reports of complex regional pain syndrome and postural orthostatic tachycardia syndrome
Date: 15 Jul 2015
Topic: Epidemiology/Etiology/Cancer Prevention
The European Medicines Agency (EMA) has started a review of human papillomavirus (HPV) vaccines to further clarify aspects of their safety profile. These vaccines have been used in around 72 million people worldwide and their use is expected to prevent many cases of cervical cancer and various other cancers and conditions caused by HPV.
Cervical cancer is the fourth most common cause of cancer death in women worldwide, with tens of thousands of deaths in Europe each year despite the existence of screening programmes to identify the cancer early.
The review does not question that the benefits of HPV vaccines outweigh their risks.
As for all licensed medicines the safety of these vaccines is monitored by the Agency’s Pharmacovigilance Risk Assessment Committee (PRAC).
The current review will look at available data with a focus on rare reports of two conditions: complex regional pain syndrome (CRPS, a chronic pain condition affecting the limbs) and postural orthostatic tachycardia syndrome (POTS, a condition where the heart rate increases abnormally after sitting or standing up, causing symptoms such as dizziness and fainting, as well as headache, chest pain and weakness).
Reports of these conditions in young women who have received an HPV vaccine have been previously considered during routine safety monitoring by the PRAC but a causal link between them and the vaccines was not established. Both conditions can occur in non-vaccinated individuals and it is considered important to further review if the number of cases reported with HPV vaccine is greater than would be expected.
In its review the PRAC will consider the latest scientific knowledge, including any research that could help clarify the frequency of CRPS and POTS following vaccination or identify any causal link. Based on this review, the Committee will decide whether to recommend any changes to product information to better inform patients and healthcare professionals.
While the review is ongoing there is no change in recommendations for the use of the vaccine.
More about the medicine
HPV vaccines are available in the European Union under the names Gardasil/Silgard, Gardasil 9, and Cervarix. Gardasil has been authorised since September 2006, and is approved in both males and females for preventing precancerous growths and cancer in the cervix and anus, and genital warts. It protects against 4 types of HPV (types 6, 11, 16 and 18). Gardasil 9 (approved in June 2015) is used similarly but protects against 9 types of the virus (6, 11, 16, 18, 31, 33, 45, 52 and 58). Cervarix has been approved since September 2007 for use in women and girls to protect against precancerous growths and cancer in the cervix and genital area. It is active against types 16 and 18 of the virus. Following their approval, the vaccines have been introduced in national immunisation programmes in many countries worldwide.
More about the procedure
The review of HPV vaccines has been initiated by the European Commission at the request of Denmark, under Article 20 of Regulation (EC) No 726/2004.
The review is being carried out by the PRAC, the Committee responsible for the evaluation of safety issues for human medicines, which will make a set of recommendations. The PRAC recommendations will then be forwarded to the Committee for Medicinal Products for Human Use (CHMP), responsible for questions concerning medicines for human use, which will adopt a final opinion. The final stage of the review procedure is the adoption by the European Commission of a legally binding decision applicable in all EU Member States.
The review will focus on rare reports of complex regional pain syndrome and postural orthostatic tachycardia syndrome
Date: 15 Jul 2015
Topic: Epidemiology/Etiology/Cancer Prevention
The European Medicines Agency (EMA) has started a review of human papillomavirus (HPV) vaccines to further clarify aspects of their safety profile. These vaccines have been used in around 72 million people worldwide and their use is expected to prevent many cases of cervical cancer and various other cancers and conditions caused by HPV.
Cervical cancer is the fourth most common cause of cancer death in women worldwide, with tens of thousands of deaths in Europe each year despite the existence of screening programmes to identify the cancer early.
The review does not question that the benefits of HPV vaccines outweigh their risks.
As for all licensed medicines the safety of these vaccines is monitored by the Agency’s Pharmacovigilance Risk Assessment Committee (PRAC).
The current review will look at available data with a focus on rare reports of two conditions: complex regional pain syndrome (CRPS, a chronic pain condition affecting the limbs) and postural orthostatic tachycardia syndrome (POTS, a condition where the heart rate increases abnormally after sitting or standing up, causing symptoms such as dizziness and fainting, as well as headache, chest pain and weakness).
Reports of these conditions in young women who have received an HPV vaccine have been previously considered during routine safety monitoring by the PRAC but a causal link between them and the vaccines was not established. Both conditions can occur in non-vaccinated individuals and it is considered important to further review if the number of cases reported with HPV vaccine is greater than would be expected.
In its review the PRAC will consider the latest scientific knowledge, including any research that could help clarify the frequency of CRPS and POTS following vaccination or identify any causal link. Based on this review, the Committee will decide whether to recommend any changes to product information to better inform patients and healthcare professionals.
While the review is ongoing there is no change in recommendations for the use of the vaccine.
More about the medicine
HPV vaccines are available in the European Union under the names Gardasil/Silgard, Gardasil 9, and Cervarix. Gardasil has been authorised since September 2006, and is approved in both males and females for preventing precancerous growths and cancer in the cervix and anus, and genital warts. It protects against 4 types of HPV (types 6, 11, 16 and 18). Gardasil 9 (approved in June 2015) is used similarly but protects against 9 types of the virus (6, 11, 16, 18, 31, 33, 45, 52 and 58). Cervarix has been approved since September 2007 for use in women and girls to protect against precancerous growths and cancer in the cervix and genital area. It is active against types 16 and 18 of the virus. Following their approval, the vaccines have been introduced in national immunisation programmes in many countries worldwide.
More about the procedure
The review of HPV vaccines has been initiated by the European Commission at the request of Denmark, under Article 20 of Regulation (EC) No 726/2004.
The review is being carried out by the PRAC, the Committee responsible for the evaluation of safety issues for human medicines, which will make a set of recommendations. The PRAC recommendations will then be forwarded to the Committee for Medicinal Products for Human Use (CHMP), responsible for questions concerning medicines for human use, which will adopt a final opinion. The final stage of the review procedure is the adoption by the European Commission of a legally binding decision applicable in all EU Member States.
lunes, 27 de julio de 2015
Palliative Chemotherapy in Patients With End-Stage Cancer
Study Shows Palliative Chemotherapy in Patients With End-Stage Cancer Did Not Improve Quality of Life and May Be Harmful
By Jo Cavallo
Posted: 7/24/2015 10:32:46 AM
Last Updated: 7/24/2015 10:32:46 AM
Although palliative chemotherapy is used to improve quality of life for patients with end-stage cancer, its use did not improve quality of life near death for patients with a moderate or poor performance status, and it worsened quality of life near death for patients with a good performance status. The treatment did not extend survival.
Prospective studies of chemotherapy use in patients with end-stage cancer are needed and should include repeated assessments of adverse effects of treatment and designate quality of life and quality of life near death as primary study endpoints.
ASCO guidelines regarding chemotherapy use in patients with terminal cancer may need to be revised to recognize the potential harm of chemotherapy use in patients with progressive metastatic disease, according to the study authors. The study by Prigerson et al is published in JAMA Oncology.
Study Methodology
The researchers examined 661 participants enrolled in a prospective multi-institutional cohort study of patients with end-stage cancer and their caregivers. Participants were recruited between September 2002 and February 2008.
Patients were required to have a diagnosis of end-stage cancer; a physician-estimated life expectancy of less than or equal to 6 months; be at least 20 years old; have a participating informal caregiver; and have adequate stamina for the interview.
A majority of the patients, 384, died during the study observation period and were more likely to be younger, nonwhite, unmarried, uninsured, less educated, and have had a worse performance status at enrollment (all P < .05) than patients who survived. Chemotherapy use at enrollment was unrelated to patients’ being in the deceased vs surviving cohort. Patients were asked to self-report age, sex, race/ethnicity, years of education, marital status, and health insurance status during baseline interviews conducted at a median of 3.8 months prior to death. Eastern Cooperative Oncology Group (ECOG) performance status was used to evaluate each patient’s performance status at enrollment. In interviews conducted a few weeks after each patient’s death, their caregivers rated the patient’s level of psychological and physical distress and overall quality of life during the patient’s final week.
Study Findings
The investigators found that chemotherapy use was not associated with patient survival, controlling for clinical setting and patients’ performance status. Among patients with a good baseline performance status (ECOG score = 1), chemotherapy use compared with nonuse was associated with worse quality of life (odds ratio [OR], 0.35; 95% CI, 0.17–0.75; P = .01). Baseline chemotherapy use was not associated with quality of life among patients with a moderate baseline performance status (ECOG score = 2; OR, 1.06; 95% CI, 0.51–2.21; P = .87) or a poor baseline performance status (ECOG score = 3; OR, 1.34; 95% CI, 0.46–3.89; P = .59).
“This study demonstrates that palliative chemotherapy does not appear to palliate symptoms, even in the most robust patients who can tolerate chemotherapy,” said Holly G. Prigerson, PhD, lead author of the study, Co-Director of the Center for Research on End-of-Life Care, and the Irving Sherwood Wright Professor in Geriatrics at Weill Cornell Medical College, in a statement. “It raises questions about the rationale for such aggressive, burdensome care.”
“Results of this study suggest that chemotherapy use among patients with chemotherapy-refractory metastatic cancer is of questionable benefit to patients’ quality of life in their final week. Not only did chemotherapy not benefit patients regardless of performance status, it appeared most harmful to those patients with good performance status. ASCO guidelines regarding chemotherapy use in patients with terminal cancer may need to be revised to recognize the potential harm of chemotherapy use in patients with progressive metastatic disease,” concluded the study authors.
Dr. Prigerson is the corresponding author of the JAMA Oncology article.
Conflicts of interest were reported by Thomas W. LeBlanc, MD, MA, who has consulted for Helsinn Therapeutics, Epi-Q, and Boehringer Ingelheim; and Alfred I. Neugut, MD, who has consulted for Pfizer, Otsuka, United Biosource Corportion, and EHE International.
Funding for this study was provided by the National Institute of Mental Health, the National Cancer Institute, the National Institute of Minority Health and Health Disparities, Weill Cornell Medical College, and the Department of Veterans Affairs.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
By Jo Cavallo
Posted: 7/24/2015 10:32:46 AM
Last Updated: 7/24/2015 10:32:46 AM
Although palliative chemotherapy is used to improve quality of life for patients with end-stage cancer, its use did not improve quality of life near death for patients with a moderate or poor performance status, and it worsened quality of life near death for patients with a good performance status. The treatment did not extend survival.
Prospective studies of chemotherapy use in patients with end-stage cancer are needed and should include repeated assessments of adverse effects of treatment and designate quality of life and quality of life near death as primary study endpoints.
ASCO guidelines regarding chemotherapy use in patients with terminal cancer may need to be revised to recognize the potential harm of chemotherapy use in patients with progressive metastatic disease, according to the study authors. The study by Prigerson et al is published in JAMA Oncology.
Study Methodology
The researchers examined 661 participants enrolled in a prospective multi-institutional cohort study of patients with end-stage cancer and their caregivers. Participants were recruited between September 2002 and February 2008.
Patients were required to have a diagnosis of end-stage cancer; a physician-estimated life expectancy of less than or equal to 6 months; be at least 20 years old; have a participating informal caregiver; and have adequate stamina for the interview.
A majority of the patients, 384, died during the study observation period and were more likely to be younger, nonwhite, unmarried, uninsured, less educated, and have had a worse performance status at enrollment (all P < .05) than patients who survived. Chemotherapy use at enrollment was unrelated to patients’ being in the deceased vs surviving cohort. Patients were asked to self-report age, sex, race/ethnicity, years of education, marital status, and health insurance status during baseline interviews conducted at a median of 3.8 months prior to death. Eastern Cooperative Oncology Group (ECOG) performance status was used to evaluate each patient’s performance status at enrollment. In interviews conducted a few weeks after each patient’s death, their caregivers rated the patient’s level of psychological and physical distress and overall quality of life during the patient’s final week.
Study Findings
The investigators found that chemotherapy use was not associated with patient survival, controlling for clinical setting and patients’ performance status. Among patients with a good baseline performance status (ECOG score = 1), chemotherapy use compared with nonuse was associated with worse quality of life (odds ratio [OR], 0.35; 95% CI, 0.17–0.75; P = .01). Baseline chemotherapy use was not associated with quality of life among patients with a moderate baseline performance status (ECOG score = 2; OR, 1.06; 95% CI, 0.51–2.21; P = .87) or a poor baseline performance status (ECOG score = 3; OR, 1.34; 95% CI, 0.46–3.89; P = .59).
“This study demonstrates that palliative chemotherapy does not appear to palliate symptoms, even in the most robust patients who can tolerate chemotherapy,” said Holly G. Prigerson, PhD, lead author of the study, Co-Director of the Center for Research on End-of-Life Care, and the Irving Sherwood Wright Professor in Geriatrics at Weill Cornell Medical College, in a statement. “It raises questions about the rationale for such aggressive, burdensome care.”
“Results of this study suggest that chemotherapy use among patients with chemotherapy-refractory metastatic cancer is of questionable benefit to patients’ quality of life in their final week. Not only did chemotherapy not benefit patients regardless of performance status, it appeared most harmful to those patients with good performance status. ASCO guidelines regarding chemotherapy use in patients with terminal cancer may need to be revised to recognize the potential harm of chemotherapy use in patients with progressive metastatic disease,” concluded the study authors.
Dr. Prigerson is the corresponding author of the JAMA Oncology article.
Conflicts of interest were reported by Thomas W. LeBlanc, MD, MA, who has consulted for Helsinn Therapeutics, Epi-Q, and Boehringer Ingelheim; and Alfred I. Neugut, MD, who has consulted for Pfizer, Otsuka, United Biosource Corportion, and EHE International.
Funding for this study was provided by the National Institute of Mental Health, the National Cancer Institute, the National Institute of Minority Health and Health Disparities, Weill Cornell Medical College, and the Department of Veterans Affairs.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
Imaging for Distant Metastases in Early-Stage Breast Cancer
Are Physicians Choosing Wisely When Imaging for Distant Metastases in Early-Stage Breast Cancer?
By Charlotte Bath
April 10, 2015, Volume 6, Issue 6
Patients with early-stage breast cancer still undergo imaging for distant metastases despite evidence-based local, national, and international guidelines—and a recommendation from ASCO—to avoid such imaging, according to a retrospective review of staging imaging for distant metastases in patients with primary early-stage breast cancer treated at a large Canadian academic cancer center.
Demetrios Simos, MD, of Ottawa Hospital Cancer Center, and colleagues reviewed 200 patient medical records, 100 from patients treated before and 100 from patients treated after publication of ASCO’s Top Five Recommendations for Choosing Wisely in Oncology in 2012. One of the recommendations was to avoid routine use of staging imaging in patients with early-stage breast cancer and no clinical findings to suggest metastatic disease.
“ASCO recommended against the routine use of staging imaging in asymptomatic patients with early-stage disease, arguing that this practice has never been shown to extend survival, is costly, and in some cases may lead to harm, because false-positive results from such tests may necessitate invasive procedures and overtreatment, all of which can impair quality of life,” the authors wrote in the Journal of Oncology Practice. They also noted that the ASCO recommendation “is in keeping with the spirit of the published guidelines.”
The mean age of patients was 60 years; 57% of tumors were self-detected; 89% were pathologic stage I or II disease, and 11% were stage III. Overall, 169 patients (84.5%) had at least one imaging test (mean, 3.6 tests per imaged patient). Of the 608 total imaging tests, 500 (82.2%) “were initial imaging tests assessing the most common metastatic sites for breast cancer (ie, skeleton, thorax, and abdomen), whereas the remaining 108 tests (17.8%) were confirmatory imaging tests,” the investigators stated.
Confirmatory imaging to clarify indeterminate initial imaging was performed in 51 (30.2%) of the 169 women undergoing imaging. None of the patients with stage I or II disease had metastatic disease detected by imaging. Metastatic disease was ultimately detected by imaging in two women, both with pathologic N3 (stage IIIC) disease detected by postoperative computed tomography (one with lung metastases and the other with liver metastases).
“Overall, 77% (154 of 200) and 75% (150 of 200) of the patients reviewed in our study underwent imaging for distant metastases, [which was] not in keeping with the spirit of the provincial guidelines and ASCO recommendations, respectively,” the researchers reported. The frequency of imaging did not change after the ASCO recommendations were published.
“Generally, the majority of patients with stage I or II disease underwent excessive imaging relative to these recommendations, and almost all patients with stage III disease underwent imaging of the skeleton, abdomen, and thorax, as recommended,” the investigators observed. Factors associated with undergoing more staging imaging than recommended included ductal histology, lower-stage disease, and a community vs academic hospital.
The lack of demonstrated benefit and the potential for harm from imaging for metastatic disease in asymptomatic patients mean that such imaging “should be avoided,” the authors concluded. “If guideline recommendations are to be implemented in practice, clearly additional knowledge translation strategies are needed beyond the simple publication of guideline documents.” ■
Simos D, et al: J Oncol Pract. November 12, 2014 (early release online).
By Charlotte Bath
April 10, 2015, Volume 6, Issue 6
Patients with early-stage breast cancer still undergo imaging for distant metastases despite evidence-based local, national, and international guidelines—and a recommendation from ASCO—to avoid such imaging, according to a retrospective review of staging imaging for distant metastases in patients with primary early-stage breast cancer treated at a large Canadian academic cancer center.
Demetrios Simos, MD, of Ottawa Hospital Cancer Center, and colleagues reviewed 200 patient medical records, 100 from patients treated before and 100 from patients treated after publication of ASCO’s Top Five Recommendations for Choosing Wisely in Oncology in 2012. One of the recommendations was to avoid routine use of staging imaging in patients with early-stage breast cancer and no clinical findings to suggest metastatic disease.
“ASCO recommended against the routine use of staging imaging in asymptomatic patients with early-stage disease, arguing that this practice has never been shown to extend survival, is costly, and in some cases may lead to harm, because false-positive results from such tests may necessitate invasive procedures and overtreatment, all of which can impair quality of life,” the authors wrote in the Journal of Oncology Practice. They also noted that the ASCO recommendation “is in keeping with the spirit of the published guidelines.”
The mean age of patients was 60 years; 57% of tumors were self-detected; 89% were pathologic stage I or II disease, and 11% were stage III. Overall, 169 patients (84.5%) had at least one imaging test (mean, 3.6 tests per imaged patient). Of the 608 total imaging tests, 500 (82.2%) “were initial imaging tests assessing the most common metastatic sites for breast cancer (ie, skeleton, thorax, and abdomen), whereas the remaining 108 tests (17.8%) were confirmatory imaging tests,” the investigators stated.
Confirmatory imaging to clarify indeterminate initial imaging was performed in 51 (30.2%) of the 169 women undergoing imaging. None of the patients with stage I or II disease had metastatic disease detected by imaging. Metastatic disease was ultimately detected by imaging in two women, both with pathologic N3 (stage IIIC) disease detected by postoperative computed tomography (one with lung metastases and the other with liver metastases).
“Overall, 77% (154 of 200) and 75% (150 of 200) of the patients reviewed in our study underwent imaging for distant metastases, [which was] not in keeping with the spirit of the provincial guidelines and ASCO recommendations, respectively,” the researchers reported. The frequency of imaging did not change after the ASCO recommendations were published.
“Generally, the majority of patients with stage I or II disease underwent excessive imaging relative to these recommendations, and almost all patients with stage III disease underwent imaging of the skeleton, abdomen, and thorax, as recommended,” the investigators observed. Factors associated with undergoing more staging imaging than recommended included ductal histology, lower-stage disease, and a community vs academic hospital.
The lack of demonstrated benefit and the potential for harm from imaging for metastatic disease in asymptomatic patients mean that such imaging “should be avoided,” the authors concluded. “If guideline recommendations are to be implemented in practice, clearly additional knowledge translation strategies are needed beyond the simple publication of guideline documents.” ■
Simos D, et al: J Oncol Pract. November 12, 2014 (early release online).
Rectal cancer treated with neoadjuvant chemoradiation RTOG 0247
Secondary analysis of RTOG 0247 demonstrates favorable overall survival rates for rectal cancer patients who received two different chemotherapy regimens concurrently with radiation therapy prior to surgery
Fairfax, Va., January 9, 2015
redjournal2_280x186.jpg
Locally advanced rectal cancer patients who receive preoperative radiation therapy with either irinotecan plus capecitabine or oxaliplatin plus capecitabine have a four-year overall survival rate of 85 percent and 75 percent, respectively, according to a study published in the January 1, 2015 issue of the International Journal of Radiation Oncology • Biology • Physics (Red Journal), the official scientific journal of the American Society for Radiation Oncology (ASTRO). This study is a secondary endpoint analysis of Radiation Therapy Oncology Group (RTOG) 0247, originally published in 20121, to evaluate long-term survival outcomes and patterns of failure.
RTOG 0247 was a randomized, Phase II multicenter trial of patients with locally advanced (T3 and T4) rectal cancer treated with neoadjuvant chemoradiation from March 2004 to February 2007. The primary endpoint analysis of RTOG 0247 examined the pathologic complete remission (pCR) rates of two concurrent neoadjuvant chemotherapy regimens to determine which regimen should be studied further. The initial results demonstrated that patients who received irinotecan plus capecitabine had lower pCR rates (10 percent compared to those who received oxaliplatin plus capecitabine (21 percent).
The study accrued 146 patients from 59 institutions from March 2004 to February 2007. All patients received preoperative pelvic radiation therapy of 50.4 Gy over five-and-a-half weeks, with 45 Gy delivered in 25 fractions (1.8 Gy per fraction, five fractions per week for five weeks) and a boost of 5.4 Gy in three fractions.
Patients were randomized to two chemotherapy treatment arms concurrent to their radiation therapy: Patients in arm 1 received concurrent chemotherapy consisting of four doses of irinotecan (50 mg/m2 IV weekly) and capecitabine (1200 mg/m2/d orally Monday through Friday during radiation therapy). Patients in arm 2 received concurrent chemotherapy consisting of five doses of oxaliplatin (50 mg/m2 IV weekly) and capecitabine (1600 mg/m2/d orally Monday through Friday during radiation therapy).
All patients in each arm had surgery four to six weeks after completion of radiation therapy, and all patients in both arms had postoperative chemotherapy of FOLFOX four to six weeks after surgery. (FOLFOX includes oxaliplatin, leucovorin; 5-fluorouacil (5-FU); and 5-FU infusion).
Both arms of the study were temporarily closed in January 2005 due to excessive gastrointestinal adverse events. The study reopened in April 2005 with an amended chemotherapy regimen. One hundred four (104) patients, 52 in each arm, were eligible and included in this analysis.
Eligible patients were at least 18 years old with a median age of 57 years; had clinical stage T3 or T4, potentially resectable adenocarcinoma of the rectum originating ≤ 12 cm from the anal verge without evidence of distant metastasis; had Zubrod performance of zero to two (the Zubrod performance scale grades patient health status from 0 to 4: a score of 0 means that the patient is “fully active, able to carry on all pre-disease performance without restriction;” and a score of 4 means that the patient is “completely disabled, cannot carry on any self-care, totally confined to a chair or bed”); and had adequate hematologic, renal, cardiac and hepatic function.
Patient evaluations occurred weekly during concurrent chemotherapy and radiation therapy, before surgery and before each cycle of postoperative chemotherapy. Follow-up was conducted every three months for the first two years post-treatment, every six months for the next three years and annually thereafter.
The median follow-up for patients in arm 1 was 3.77 years (range 0.19 to 5.23 years), and the median follow-up for patients in arm 2 was 3.97 years (range 0.44 to 5.15 years).
The new study’s analysis of RTOG 0247’s long-term data found that at four-year follow-up, patients in arm 1 (irinotecan plus capecitabine) had an overall survival (OS) rate of 85 percent (44); a disease-free survival (DFS) rate of 68 percent (35), a local-regional failure (LRF) rate of 16 percent (8), a distant failure (DF) rate of 24 percent (12) and a second/new primary failure (SP) rate of 2 percent (1).
At four-year follow-up, patients in arm 2 (oxaliplatin plus capecitabine) had an OS rate of 75 percent (39), a DFS rate of 62 percent (32), a LRF rate of 18 percent (9), a DF rate of 30 percent (16) and an SP rate of 6 percent (3). All measures had a 95 percent confidence interval.
“Our new analysis of RTOG 0247 provides us with favorable efficacy results of two preoperative chemotherapy regimens used in conjunction with radiation therapy protocols,” said Neal J. Meropol, MD, co-author of the study, and the Dr. Lester E. Coleman Jr., Professor of Cancer Research and Therapeutics and chief of the Division of Hematology and Oncology at University Hospitals Case Medical Center and Case Western Reserve University in Cleveland.
“These favorable long-term survival rates confirm that both of these concurrent chemoradiotherapy regimens followed by surgery can be a highly curative approach for patients with localized rectal cancer, despite the low pCR results we reported in 2012. It is important to find new biomarkers beyond the local remission rate that can help us determine which patients will be cured and who may benefit from more aggressive therapy following chemoradiation.”
For a copy of the study manuscript, contact ASTRO’s Press Office. Learn more about the Red Journal.
1 Wong SJ, Winter K, Meropol NJ, et al. Radiation therapy oncology group 0247: A randomized phase II study of neoadjuvant capecitabine and irinotecan or capecitabine and oxaliplatin with concurrent radiotherapy for patients with locally advanced rectal cancer. Int J Radiat Oncol Biol Phys. 2012; 82: 1367-1375.
Fairfax, Va., January 9, 2015
redjournal2_280x186.jpg
Locally advanced rectal cancer patients who receive preoperative radiation therapy with either irinotecan plus capecitabine or oxaliplatin plus capecitabine have a four-year overall survival rate of 85 percent and 75 percent, respectively, according to a study published in the January 1, 2015 issue of the International Journal of Radiation Oncology • Biology • Physics (Red Journal), the official scientific journal of the American Society for Radiation Oncology (ASTRO). This study is a secondary endpoint analysis of Radiation Therapy Oncology Group (RTOG) 0247, originally published in 20121, to evaluate long-term survival outcomes and patterns of failure.
RTOG 0247 was a randomized, Phase II multicenter trial of patients with locally advanced (T3 and T4) rectal cancer treated with neoadjuvant chemoradiation from March 2004 to February 2007. The primary endpoint analysis of RTOG 0247 examined the pathologic complete remission (pCR) rates of two concurrent neoadjuvant chemotherapy regimens to determine which regimen should be studied further. The initial results demonstrated that patients who received irinotecan plus capecitabine had lower pCR rates (10 percent compared to those who received oxaliplatin plus capecitabine (21 percent).
The study accrued 146 patients from 59 institutions from March 2004 to February 2007. All patients received preoperative pelvic radiation therapy of 50.4 Gy over five-and-a-half weeks, with 45 Gy delivered in 25 fractions (1.8 Gy per fraction, five fractions per week for five weeks) and a boost of 5.4 Gy in three fractions.
Patients were randomized to two chemotherapy treatment arms concurrent to their radiation therapy: Patients in arm 1 received concurrent chemotherapy consisting of four doses of irinotecan (50 mg/m2 IV weekly) and capecitabine (1200 mg/m2/d orally Monday through Friday during radiation therapy). Patients in arm 2 received concurrent chemotherapy consisting of five doses of oxaliplatin (50 mg/m2 IV weekly) and capecitabine (1600 mg/m2/d orally Monday through Friday during radiation therapy).
All patients in each arm had surgery four to six weeks after completion of radiation therapy, and all patients in both arms had postoperative chemotherapy of FOLFOX four to six weeks after surgery. (FOLFOX includes oxaliplatin, leucovorin; 5-fluorouacil (5-FU); and 5-FU infusion).
Both arms of the study were temporarily closed in January 2005 due to excessive gastrointestinal adverse events. The study reopened in April 2005 with an amended chemotherapy regimen. One hundred four (104) patients, 52 in each arm, were eligible and included in this analysis.
Eligible patients were at least 18 years old with a median age of 57 years; had clinical stage T3 or T4, potentially resectable adenocarcinoma of the rectum originating ≤ 12 cm from the anal verge without evidence of distant metastasis; had Zubrod performance of zero to two (the Zubrod performance scale grades patient health status from 0 to 4: a score of 0 means that the patient is “fully active, able to carry on all pre-disease performance without restriction;” and a score of 4 means that the patient is “completely disabled, cannot carry on any self-care, totally confined to a chair or bed”); and had adequate hematologic, renal, cardiac and hepatic function.
Patient evaluations occurred weekly during concurrent chemotherapy and radiation therapy, before surgery and before each cycle of postoperative chemotherapy. Follow-up was conducted every three months for the first two years post-treatment, every six months for the next three years and annually thereafter.
The median follow-up for patients in arm 1 was 3.77 years (range 0.19 to 5.23 years), and the median follow-up for patients in arm 2 was 3.97 years (range 0.44 to 5.15 years).
The new study’s analysis of RTOG 0247’s long-term data found that at four-year follow-up, patients in arm 1 (irinotecan plus capecitabine) had an overall survival (OS) rate of 85 percent (44); a disease-free survival (DFS) rate of 68 percent (35), a local-regional failure (LRF) rate of 16 percent (8), a distant failure (DF) rate of 24 percent (12) and a second/new primary failure (SP) rate of 2 percent (1).
At four-year follow-up, patients in arm 2 (oxaliplatin plus capecitabine) had an OS rate of 75 percent (39), a DFS rate of 62 percent (32), a LRF rate of 18 percent (9), a DF rate of 30 percent (16) and an SP rate of 6 percent (3). All measures had a 95 percent confidence interval.
“Our new analysis of RTOG 0247 provides us with favorable efficacy results of two preoperative chemotherapy regimens used in conjunction with radiation therapy protocols,” said Neal J. Meropol, MD, co-author of the study, and the Dr. Lester E. Coleman Jr., Professor of Cancer Research and Therapeutics and chief of the Division of Hematology and Oncology at University Hospitals Case Medical Center and Case Western Reserve University in Cleveland.
“These favorable long-term survival rates confirm that both of these concurrent chemoradiotherapy regimens followed by surgery can be a highly curative approach for patients with localized rectal cancer, despite the low pCR results we reported in 2012. It is important to find new biomarkers beyond the local remission rate that can help us determine which patients will be cured and who may benefit from more aggressive therapy following chemoradiation.”
For a copy of the study manuscript, contact ASTRO’s Press Office. Learn more about the Red Journal.
1 Wong SJ, Winter K, Meropol NJ, et al. Radiation therapy oncology group 0247: A randomized phase II study of neoadjuvant capecitabine and irinotecan or capecitabine and oxaliplatin with concurrent radiotherapy for patients with locally advanced rectal cancer. Int J Radiat Oncol Biol Phys. 2012; 82: 1367-1375.
domingo, 26 de julio de 2015
Attacking Angiogenesis Anew
Attacking Angiogenesis Anew: Novel Agents and Strategies Keep Focus on Complex Cancer Hallmark
Jane de Lartigue, PhD
Published Online: Friday, October 10, 2014
A decade after bevacizumab (Avastin) debuted as the first anticancer therapy to target angiogenesis, new strategies to attack this hallmark of cancer continue to be a major research focus, resulting in the development of novel agents and fresh treatment settings for existing drugs.
Earlier this year, the FDA approved ramucirumab (Cyramza) for the treatment of patients with advanced gastric or gastroesophageal junction adenocarcinoma that progresses after prior therapies. Additional expansion in this field has come from new indications for previously approved agents, including bevacizumab, and several novel agents hold particular promise as treatments for gynecologic malignancies and non–small cell lung cancer (NSCLC).
Yet despite these advances, researchers are far from reaching a complete understanding of the intricacies of tumor vasculature, and significant barriers prevent antiangiogenic therapy from reaching its full potential.
Forming New Blood Vessels From Old
In contrast to neovascularization, in which new blood vessels are formed from circulating precursor endothelial cells, angiogenesis is the formation of new blood vessels from preexisting ones. While the former occurs predominantly during early development to establish a primitive vascular network, the latter allows for expansion of this network through branching, remodeling, and maturation.
In adults, a delicate balance between pro- and antiangiogenic signaling pathways is maintained so that angiogenesis is only switched on when required for physiological processes such as wound healing or menstruation.
The central angiogenic signaling pathway is governed by the vascular endothelial growth factor receptor (VEGFR). Three VEGFRs (VEGFR 1, 2, and 3) mediate the effects of their ligands; these ligands comprise a family of secreted growth factors, VEGF A through E, that induce proliferation and migration of endothelial cells, the primary cell type involved in the formation of new blood vessels.
What a Tangled Web It Weaves
In the early 1970s, Judah Folkman, MD, who was posthumously honored with a Giants of Cancer Care Award last year, became the founding father of the field of tumor angiogenesis with the observation that tumors are unable to grow beyond a cluster of cells of 2 mm to 3 mm without establishing their own vascular network. Beyond this size, the cells at the outermost perimeter of the tumor are far from the blood supply and begin to be starved of oxygen and nutrients.
In response to their hypoxic environment and genetic alterations that are common in cancer, it is believed that cancer cells induce an angiogenic switch; the cells of the tumor and its microenvironment begin to secrete angiogenic growth and survival factors that tip the balance toward proangiogenic signaling pathways, such as the VEGFR pathway. The new blood vessels are unlike normal vasculature; they are poorly developed, chaotic, and tortuous, which results in aberrant functions.
Key Angiogenesis Elements and Agents
FLT indicates Fms-like tyrosine kinase; KIT, mast/stem cell growth factor receptor; MAPK, mitogen-activated protein kinase; PDGFR, platelet-derived growth factor receptor; PRKC, protein kinase C; RAF1, proto-oncogene c-RAF; VEGF, vascular endothelial growth factor; VEGFR, vascular endothelial growth factor receptor.
Wehland M et al. Biomarkers for anti-angiogenic therapy. Int J Mol Sci. 2013;14(5):9338-9364. http://goo.gl/MdALSj. Adapted with permission.
- See more at: http://www.onclive.com/publications/Oncology-live/2014/October-2014/Attacking-Angiogenesis-Anew-Novel-Agents-and-Strategies-Keep-Focus-on-Complex-Cancer-Hallmark#sthash.W78ONqul.dpuf
The establishment of new blood vessels supplies the tumor with oxygen and nutrients, while at the same time providing a potential route for metastasis. In subsequent years, the key role of tumor angiogenesis was cemented when Douglas Hanahan and Robert Weinberg named the process as one of the essential biological capabilities required for the transformation of a normal cell to a cancerous one.
Many Roles for Bevacizumab
Given its critical role in angiogenic signaling, the VEGFR pathway has been a substantial focus for the development of therapies that would target aberrant signaling, prevent the formation of tumor vasculature, and cut off tumor blood supply.
In 2004, the FDA approved bevacizumab, a monoclonal antibody targeting VEGF-A, for the first-line treatment of metastatic colorectal cancer in combination with standard chemotherapy. It is now approved in a number of other tumor types and settings (Table).
Most recently, the FDA approved bevacizumab in combination with paclitaxel plus either cisplatin or topotecan as a treatment for patients with persistent, recurrent, or metastatic cervical cancer, based on the extension of overall survival (OS) in the GOG 240 study. Bevacizumab combined with chemotherapy increased OS to 16.8 months compared with 12.9 months for chemotherapy alone.
The FDA also is considering a new indication for bevacizumab in patients with recurrent, platinumresistant ovarian cancer. The agency granted the drug priority review status based on the phase III AURELIA trial, which demonstrated that bevacizumab with chemotherapy reduced the risk of disease progression by 52% compared with chemotherapy alone (6.7 months vs 3.4 months; HR = 0.48).
And in breast cancer, findings from two phase III trials presented at the 2014 ESMO Congress in September support the use of bevacizumab for patients with HER2-negative metastatic disease.
In the IMELDA study, the addition of capecitabine to maintenance bevacizumab resulted in a statistically significant advantage in median progression-free survival (PFS) compared with bevacizumab alone (11.9 months vs 4.3 months, respectively). In the TANIA trial, continuing or reintroducing bevacizumab to patients receiving chemotherapy after progression on first-line bevacizumab improved PFS compared with chemotherapy alone (6.3 months vs 4.2 months).
Notably, the FDA had approved bevacizumab in combination with paclitaxel in metastatic HER2-negative breast cancer in 2008 but revoked the indication about 3½ years later after concluding that the benefits did not outweigh the potential risks.
Search for Single-Agent Efficacy
Despite its established use in a range of cancer types, bevacizumab has limited efficacy as a single agent and its effects in combination with chemotherapy are often transient. Efforts to improve on the single-agent efficacy of antiangiogenic therapies have driven the creation of a number of other agents that target this process.
These include multitargeted tyrosine kinase inhibitors (TKIs), which are aimed at TKI receptors that play a key role in angiogenic signaling pathways, including platelet-derived growth factor receptors (PDGFRs) and fibroblast growth factor receptors (FGFRs).
First-generation TKIs include sorafenib (Nexavar), sunitinib (Sutent), and pazopanib (Votrient), which have shown efficacy in the treatment of renal cell carcinoma and other cancer types (Table). They continue to be evaluated in clinical trials, with varied success. In recent years, the FDA has approved several second- generation multitargeted TKIs, including axitinib (Inlyta), regorafenib (Stivarga), and vandetanib (Caprelsa). These agents also are the focus of ongoing phase III trials.
Finally, several multitargeted novel agents are being evaluated in late-state clinical testing. Like regorafenib, nintedanib and cediranib target FGFR in addition to VEGFR and PDGFR, while dovitinib is a TKI that targets solely FGFR3.
Nintedanib is pending approval from the European Medicines Agency in combination with docetaxel for patients with locally advanced, metastatic, or recurrent adenocarcinoma NSCLC after first-line chemotherapy.
Promising data from the randomized phase III LUME-Lung 1 trial, which involved 1314 patients, were presented at ESMO. After a prespecified number of events, there was a significant PFS improvement among patients who received nintedanib plus docetaxel as second-line therapy compared with those who received placebo plus docetaxel (3.4 months vs 2.7 months; P = .0019). An OS improvement reached statistical significance among patients with adenocarcinoma histology (HR = 0.83) and in patients with fast-growing adenocarcinoma (HR = 0.75), but not among the population as a whole.
Cediranib, on the other hand, failed in phase II trials and did not progress to phase III development for patients with NSCLC, but continues to be evaluated in a number of other cancer types. Phase II data presented at the 2014 American Society of Clinical Oncology Annual Meeting demonstrated that combining cediranib with the PARP inhibitor olaparib resulted in a neardoubling of median PFS among women with recurrent ovarian cancer compared with olaparib alone (17.7 months vs 9 months).
Meanwhile, dovitinib failed to show improvement over sorafenib in patients with metastatic RCC in phase III trial results reported last year, but remains under active investigation in other treatment settings.
Continuing Focus on VEGFR
VEGFR signaling remains a prime target for antiangiogenic therapy, and several of the next-generation antiangiogenic agents also target this pathway, but in ways than differ from bevacizumab. Ramucirumab is a monoclonal antibody like bevacizumab, but targets the receptor VEGFR2 rather than the ligand. In April, the FDA approved ramucirumab as a single agent for the treatment of advanced/metastatic gastric or gastroesophageal junction adenocarcinoma that has progressed after chemotherapy. Clinical trial findings demonstrated improved OS (5.2 months vs 3.8 months) for ramucirumab plus best supportive care (BSC) compared with placebo plus BSC among 355 patients with disease progression following fluoropyrimidine- or platinum-containing chemotherapy. - See more at: http://www.onclive.com/publications/oncology-live/2014/october-2014/attacking-angiogenesis-anew-novel-agents-and-strategies-keep-focus-on-complex-cancer-hallmark/2#sthash.D2nJRHAt.dpuf
- See more at: http://www.onclive.com/publications/Oncology-live/2014/October-2014/Attacking-Angiogenesis-Anew-Novel-Agents-and-Strategies-Keep-Focus-on-Complex-Cancer-Hallmark#sthash.W78ONqul.dpuf
Jane de Lartigue, PhD
Published Online: Friday, October 10, 2014
A decade after bevacizumab (Avastin) debuted as the first anticancer therapy to target angiogenesis, new strategies to attack this hallmark of cancer continue to be a major research focus, resulting in the development of novel agents and fresh treatment settings for existing drugs.
Earlier this year, the FDA approved ramucirumab (Cyramza) for the treatment of patients with advanced gastric or gastroesophageal junction adenocarcinoma that progresses after prior therapies. Additional expansion in this field has come from new indications for previously approved agents, including bevacizumab, and several novel agents hold particular promise as treatments for gynecologic malignancies and non–small cell lung cancer (NSCLC).
Yet despite these advances, researchers are far from reaching a complete understanding of the intricacies of tumor vasculature, and significant barriers prevent antiangiogenic therapy from reaching its full potential.
Forming New Blood Vessels From Old
In contrast to neovascularization, in which new blood vessels are formed from circulating precursor endothelial cells, angiogenesis is the formation of new blood vessels from preexisting ones. While the former occurs predominantly during early development to establish a primitive vascular network, the latter allows for expansion of this network through branching, remodeling, and maturation.
In adults, a delicate balance between pro- and antiangiogenic signaling pathways is maintained so that angiogenesis is only switched on when required for physiological processes such as wound healing or menstruation.
The central angiogenic signaling pathway is governed by the vascular endothelial growth factor receptor (VEGFR). Three VEGFRs (VEGFR 1, 2, and 3) mediate the effects of their ligands; these ligands comprise a family of secreted growth factors, VEGF A through E, that induce proliferation and migration of endothelial cells, the primary cell type involved in the formation of new blood vessels.
What a Tangled Web It Weaves
In the early 1970s, Judah Folkman, MD, who was posthumously honored with a Giants of Cancer Care Award last year, became the founding father of the field of tumor angiogenesis with the observation that tumors are unable to grow beyond a cluster of cells of 2 mm to 3 mm without establishing their own vascular network. Beyond this size, the cells at the outermost perimeter of the tumor are far from the blood supply and begin to be starved of oxygen and nutrients.
In response to their hypoxic environment and genetic alterations that are common in cancer, it is believed that cancer cells induce an angiogenic switch; the cells of the tumor and its microenvironment begin to secrete angiogenic growth and survival factors that tip the balance toward proangiogenic signaling pathways, such as the VEGFR pathway. The new blood vessels are unlike normal vasculature; they are poorly developed, chaotic, and tortuous, which results in aberrant functions.
Key Angiogenesis Elements and Agents
FLT indicates Fms-like tyrosine kinase; KIT, mast/stem cell growth factor receptor; MAPK, mitogen-activated protein kinase; PDGFR, platelet-derived growth factor receptor; PRKC, protein kinase C; RAF1, proto-oncogene c-RAF; VEGF, vascular endothelial growth factor; VEGFR, vascular endothelial growth factor receptor.
Wehland M et al. Biomarkers for anti-angiogenic therapy. Int J Mol Sci. 2013;14(5):9338-9364. http://goo.gl/MdALSj. Adapted with permission.
- See more at: http://www.onclive.com/publications/Oncology-live/2014/October-2014/Attacking-Angiogenesis-Anew-Novel-Agents-and-Strategies-Keep-Focus-on-Complex-Cancer-Hallmark#sthash.W78ONqul.dpuf
The establishment of new blood vessels supplies the tumor with oxygen and nutrients, while at the same time providing a potential route for metastasis. In subsequent years, the key role of tumor angiogenesis was cemented when Douglas Hanahan and Robert Weinberg named the process as one of the essential biological capabilities required for the transformation of a normal cell to a cancerous one.
Many Roles for Bevacizumab
Given its critical role in angiogenic signaling, the VEGFR pathway has been a substantial focus for the development of therapies that would target aberrant signaling, prevent the formation of tumor vasculature, and cut off tumor blood supply.
In 2004, the FDA approved bevacizumab, a monoclonal antibody targeting VEGF-A, for the first-line treatment of metastatic colorectal cancer in combination with standard chemotherapy. It is now approved in a number of other tumor types and settings (Table).
Most recently, the FDA approved bevacizumab in combination with paclitaxel plus either cisplatin or topotecan as a treatment for patients with persistent, recurrent, or metastatic cervical cancer, based on the extension of overall survival (OS) in the GOG 240 study. Bevacizumab combined with chemotherapy increased OS to 16.8 months compared with 12.9 months for chemotherapy alone.
The FDA also is considering a new indication for bevacizumab in patients with recurrent, platinumresistant ovarian cancer. The agency granted the drug priority review status based on the phase III AURELIA trial, which demonstrated that bevacizumab with chemotherapy reduced the risk of disease progression by 52% compared with chemotherapy alone (6.7 months vs 3.4 months; HR = 0.48).
And in breast cancer, findings from two phase III trials presented at the 2014 ESMO Congress in September support the use of bevacizumab for patients with HER2-negative metastatic disease.
In the IMELDA study, the addition of capecitabine to maintenance bevacizumab resulted in a statistically significant advantage in median progression-free survival (PFS) compared with bevacizumab alone (11.9 months vs 4.3 months, respectively). In the TANIA trial, continuing or reintroducing bevacizumab to patients receiving chemotherapy after progression on first-line bevacizumab improved PFS compared with chemotherapy alone (6.3 months vs 4.2 months).
Notably, the FDA had approved bevacizumab in combination with paclitaxel in metastatic HER2-negative breast cancer in 2008 but revoked the indication about 3½ years later after concluding that the benefits did not outweigh the potential risks.
Search for Single-Agent Efficacy
Despite its established use in a range of cancer types, bevacizumab has limited efficacy as a single agent and its effects in combination with chemotherapy are often transient. Efforts to improve on the single-agent efficacy of antiangiogenic therapies have driven the creation of a number of other agents that target this process.
These include multitargeted tyrosine kinase inhibitors (TKIs), which are aimed at TKI receptors that play a key role in angiogenic signaling pathways, including platelet-derived growth factor receptors (PDGFRs) and fibroblast growth factor receptors (FGFRs).
First-generation TKIs include sorafenib (Nexavar), sunitinib (Sutent), and pazopanib (Votrient), which have shown efficacy in the treatment of renal cell carcinoma and other cancer types (Table). They continue to be evaluated in clinical trials, with varied success. In recent years, the FDA has approved several second- generation multitargeted TKIs, including axitinib (Inlyta), regorafenib (Stivarga), and vandetanib (Caprelsa). These agents also are the focus of ongoing phase III trials.
Finally, several multitargeted novel agents are being evaluated in late-state clinical testing. Like regorafenib, nintedanib and cediranib target FGFR in addition to VEGFR and PDGFR, while dovitinib is a TKI that targets solely FGFR3.
Nintedanib is pending approval from the European Medicines Agency in combination with docetaxel for patients with locally advanced, metastatic, or recurrent adenocarcinoma NSCLC after first-line chemotherapy.
Promising data from the randomized phase III LUME-Lung 1 trial, which involved 1314 patients, were presented at ESMO. After a prespecified number of events, there was a significant PFS improvement among patients who received nintedanib plus docetaxel as second-line therapy compared with those who received placebo plus docetaxel (3.4 months vs 2.7 months; P = .0019). An OS improvement reached statistical significance among patients with adenocarcinoma histology (HR = 0.83) and in patients with fast-growing adenocarcinoma (HR = 0.75), but not among the population as a whole.
Cediranib, on the other hand, failed in phase II trials and did not progress to phase III development for patients with NSCLC, but continues to be evaluated in a number of other cancer types. Phase II data presented at the 2014 American Society of Clinical Oncology Annual Meeting demonstrated that combining cediranib with the PARP inhibitor olaparib resulted in a neardoubling of median PFS among women with recurrent ovarian cancer compared with olaparib alone (17.7 months vs 9 months).
Meanwhile, dovitinib failed to show improvement over sorafenib in patients with metastatic RCC in phase III trial results reported last year, but remains under active investigation in other treatment settings.
Continuing Focus on VEGFR
VEGFR signaling remains a prime target for antiangiogenic therapy, and several of the next-generation antiangiogenic agents also target this pathway, but in ways than differ from bevacizumab. Ramucirumab is a monoclonal antibody like bevacizumab, but targets the receptor VEGFR2 rather than the ligand. In April, the FDA approved ramucirumab as a single agent for the treatment of advanced/metastatic gastric or gastroesophageal junction adenocarcinoma that has progressed after chemotherapy. Clinical trial findings demonstrated improved OS (5.2 months vs 3.8 months) for ramucirumab plus best supportive care (BSC) compared with placebo plus BSC among 355 patients with disease progression following fluoropyrimidine- or platinum-containing chemotherapy. - See more at: http://www.onclive.com/publications/oncology-live/2014/october-2014/attacking-angiogenesis-anew-novel-agents-and-strategies-keep-focus-on-complex-cancer-hallmark/2#sthash.D2nJRHAt.dpuf
- See more at: http://www.onclive.com/publications/Oncology-live/2014/October-2014/Attacking-Angiogenesis-Anew-Novel-Agents-and-Strategies-Keep-Focus-on-Complex-Cancer-Hallmark#sthash.W78ONqul.dpuf
miércoles, 22 de julio de 2015
MRI Breast Cancer Screening
Optimizing MRI Breast Cancer Screening: A Multidisciplinary Perspective CME
Therese B. Bevers, MD; Parijatham S. Thomas, MD; Habib Rahbar, MD; Erin I. Neuschler, MD
Breast Cancer Screening Using MRI Technology
Although mammography remains the gold standard for detecting breast cancer, it has been reported to miss up to 40,000 to 45,000 breast cancers each year.[1] It therefore may not be a sufficient screening tool for women at high risk of developing breast cancer (≥20% risk). Clinical trials have shown magnetic resonance imaging (MRI) to significantly improve the detection of cancers that are otherwise clinically, mammographically, and sonographically occult, leading the American College of Radiology (ACR) and the American Cancer Society (ACS) to recommend the use of breast screening MRI as an adjunct to mammography to improve breast cancer surveillance in high-risk women.[2-4] There are currently no recommendations for or against breast MRI in women at mild or moderately increased risk (15%-20%) of developing breast cancer because the benefits in this population remain unclear.[3]
Clinical Utility of MRI vs Mammography
Mammograms use low doses of radiation to produce x-ray images of the breast. Because x-rays are not able to effectively penetrate dense breast tissue, these images can be more difficult to obtain and read when patients have dense breasts. Compared with mammography, MRI is more sensitive in detecting breast abnormalities. It uses magnetic fields to produce cross-sectional images of soft-tissue structures. The contrast between lesions and normal tissues of the breast, such as adipose and fibroglandular, depends on the mobility and magnetic environment of the hydrogen atoms in the water and fat of these tissues. Gadolinium-based contrast agents (GBCAs) are injected intravenously to improve detection of cancers and other lesions, and studies have shown contrast-enhanced MRI to have a high sensitivity for detecting breast cancers,[5-7] making it a beneficial screening tool for women who are at high risk of developing breast cancer, particularly in the setting of dense breast tissue.
Several large, prospective, nonrandomized studies have been conducted worldwide to evaluate the efficacy of adding breast screening MRIs to annual mammography in women at high risk of developing breast cancer (Table 1).[8-12] These studies included women with BRCA1 or BRCA2 gene mutations or a strong family history of breast cancer. Although patient population characteristics and techniques in obtaining breast MRI varied between studies, all studies showed MRI to have a higher sensitivity in detecting breast cancer compared with mammography. Of the studies that had more than 1 round of screening, interval cancer rates were less than 10%.[8-10,12]
Table 1. Summary of 5 Published Breast MRI Screening Studies[4]
The Netherlands Canada United Kingdom Germany United States
Sensitivity (%)
MRI 80 77 77 91 100
Mammogram 33 36 40 33 25
Ultrasound N/A 33 N/A 40 N/A
Specificity (%)
MRI 90 95 81 97 95
Mammogram 95 >99 93 97 98
Ultrasound N/A 96 N/A 91 N/A
N/A = not applicable.
From Saslow D, et al.[4]
Although breast MRI can detect smaller tumors than mammography, it has limitations. Due to its lower specificity and higher sensitivity, callback rates for additional imaging and biopsy have been higher with MRI in high-risk populations, ranging from 8% to 17% for imaging and 3% to 15% for biopsy.[8-12] However, recall rates decreased with subsequent rounds of screening. Increased callback and biopsy rates can lead to increased patient anxiety, which has the potential to adversely affect women's future compliance with screening, but it can also increase the number of detected cancers.
Cost-Effectiveness of Breast MRI
The cost-effectiveness of adding breast MRI to annual mammography has been evaluated in different high-risk cohorts. Plevritis and colleagues reported that the addition of breast MRI was cost-effective in BRCA1 and BRCA2 mutation carriers but that the cost per quality-adjusted life year (QALY) was greater in women with BRCA1 mutations and varied greatly with age, though the cost benefits were greatest in patients aged 40 to 49 years for both mutation types.[13] The increased cost savings in the BRCA1 group was attributed to these mutations having a higher risk for cancer, including more aggressive cancers, compared with BRCA2 mutations.[13,14]
A 2014 study by Ahern and colleagues evaluated the cost-effectiveness for various schedules integrating screening MRI with mammography in women with a strong family history of breast cancer and a lifetime risk of 25% or higher.[15] Based on current MRI costs and an incremental cost-effectiveness ratio of $100,000 per QALY, they found the most cost-effective strategy was to stagger MRI and mammography plus clinical breast exam every year from age 30 to 74 for women who had a 25% lifetime risk of breast cancer. For those with a 50% lifetime risk, the recommended strategy was to follow the same screening protocol but to stagger these examinations every 6 months, provided there was a 70% reduction in MRI costs. At 75% risk, the recommended strategy became biennial MRI combined with mammography plus clinical breast exam every 6 months.[15] Although screening MRIs may eventually become routine in breast cancer surveillance, their high cost is currently a major factor restricting their use to those deemed to be at sufficiently high risk of developing breast cancer.
Identifying the High-Risk Patient
Based on the current literature, the ACS has established guidelines recommending breast MRI as an adjunct to annual mammography in specific groups of women at high risk (≥20% risk) of developing breast cancer (Table 2).[3] Identifying these high-risk patients requires careful consideration of several key risk factors, including a strong family history of breast cancer, the presence of BRCA1 and/or BRCA2 gene mutations, and exposure to certain types of radiation.
Table 2. American Cancer Society's Recommendations for Annual Breast Screening MRIs
Patients Who Should Receive Annual MRI Screenings
Have BRCA1 or BRCA2 mutations
First-degree relative is a BRCA carrier, but patient's BRCA status is unknown
Lifetime risk of breast cancer is ≥20%, as determined by risk assessment tools based predominantly on family history
History of chest irradiation between the ages of 10 and 30
Have Li-Fraumeni syndrome, Cowden syndrome, or Bannayan-Riley-Ruvalcaba syndrome, or have a first-degree relative with one of these syndromes
Patients With Insufficient Evidence to Make Recommendation for or Against Annual MRI Screenings
Lifetime risk of breast cancer between 15% and 20%, as defined by risk assessment tools based predominantly on family history
Heterogeneously or extremely dense breasts on mammography
History of benign breast lesions that increase the risk of breast cancer, including lobular carcinoma in situ, atypical lobular hyperplasia, and atypical ductal hyperplasia
History of breast cancer, including ductal carcinoma in situ
Patients Who Should Not Receive MRI Screenings
Lifetime risk of breast cancer is <15%
Family History
Because breast cancer is the most common cancer among women, many women in the general population will have at least 1 relative with breast cancer. However, this alone does not confer an increased risk of developing breast cancer because only 5% to 10% of all breast cancers are thought to be hereditary.[3] These heritable cases are attributable to mutations in several highly penetrant susceptibility genes, of which BRCA1 and BRCA2 are currently the best recognized. Women who carry a genetic mutation in these genes can have up to a 65% lifetime risk of developing breast cancer and also have an increased risk of developing ovarian cancer.[14,16,17]
Family history factors that increase the likelihood of a patient having a BRCA1 or BRCA2 mutation are outlined in Table 3. According to the ACS 2007 breast cancer screening guidelines, several risk assessment models can be used to estimate lifetime breast cancer risk (ie, Gail, Claus, and Tyrer-Cusick models) or the likelihood that a BRCA gene mutation is present (ie, BRCAPro and BOADICEA).[4] Although all of these models depend heavily on family history, they also consider a combination of other risk factors (eg, age, reproductive history, previous breast biopsy); thus, an individual woman's risk estimate may vary with different models.[4]
Table 3. Family History Factors Suggestive of an Increased Risk for BRCA1 or BRCA2 Mutations
≥ 2 first- or second-degree relatives with breast or ovarian cancer
Breast cancer occurring in premenopausal women and/or those diagnosed before age 50 years
Cases of male breast cancer
Simultaneous breast and ovarian cancers or 2 primary breast cancers in the same woman or the same family
Two or more types of BRCA1- or BRCA2-related cancers in a single family member
Ashkenazi Jewish ancestry
Genetic counseling should be considered for women who are found to be at increased risk of having a BRCA gene mutation or developing breast cancer. Women who undergo genetic testing and are found to carry BRCA1 or BRCA2 mutations, or who have other high-penetrance genes for familial cancer syndromes, such as PTEN and p53, should have increased surveillance with breast MRI in addition to annual mammography and clinical breast exams. Women who do not have the aforementioned genetic mutations or who choose not to undergo testing but have a strong family history of breast or ovarian cancer and a more than 20% lifetime risk of developing these cancers should also receive adjunct breast screening MRIs.[4]
Exposure to Mantle Field Radiation
Another known risk factor for breast cancer is exposure to mantle field radiation, which is used as a treatment for Hodgkin lymphoma.[18] A study by Tinger and colleagues showed the incidence of breast cancer in this population to be highest for women treated in the 1960s to mid-1970s compared with those treated in the late 1970s to mid-1980s, when radiation protocols were changed to administer lower doses, with the risk dissipating in the latter group after a median follow-up of 13 years.[19] These findings suggest that Hodgkin disease survivors treated with current approaches are unlikely to have a substantially increased risk of breast cancer. Nevertheless, it is thought that these women may derive the same benefit from breast screening MRIs as women with a strong family history due to their higher risk of a secondary breast cancer. The ACS and ACR guidelines include women with Hodgkin disease or a history of mantle field radiation in their high-risk category and recommend breast screening MRIs in these women.[2-4]
Other High-Risk Groups
In 2006, a meta-analysis showed breast density to be an independent risk factor for breast cancer, with women with dense breasts having a 4- to 5-fold increased risk compared with other women.[20] As previously noted, dense tissue may also make it difficult to identify masses on mammography, necessitating further imaging for cancer detection.
Atypical hyperplasia and lobular carcinoma in situ are high-risk lesions found in approximately 10% of benign biopsies.[21] Studies have shown that the lifetime risk of breast cancer in women with these benign lesions is 30% at 25 years of follow-up.[22-24] Although the level of lifetime risk in these women is higher than the current standard needed for breast MRI screening, breast MRI is currently not recommended due to insufficient data.
Women with a personal history of breast cancer are also at high risk of developing a recurrence or a second breast cancer. Annual mammography is recommended after treatment, but increased screening based on the patient's cancer history and tumor characteristics should be considered.
Collaborative Approaches
Screening for breast cancer has been a topic of debate and a source of high anxiety for women. To optimize breast screening MRIs, a collaborative approach among clinicians and radiologists should be undertaken to improve efficiency and reduce patient anxiety, particularly as breast cancer screening becomes more complex with additional imaging. Coordination of visits and imaging on the same day improves efficiency and can lead to decreased expenses and travel time. Also, allowing for increased imaging and additional views, if needed, during the same mammography or MRI appointment can reduce patient anxiety and the need for additional visits.
Because current ACS recommendations for breast MRI screening do not address the timing of MRI in conjunction with mammography, clinicians and radiologists should develop screening protocols in their community for women at high risk for breast cancer. Ideally, these protocols should include breast MRI for patients who have a more than 20% lifetime risk of developing breast cancer. Alternating imaging between MRI and mammography so that patients are screened more frequently may increase the chance of earlier detection of aggressive and lower-stage cancers.
Brachytherapy Yields Better Survival in Endometrial Cancer
From Medscape Education Clinical Briefs
Brachytherapy Yields Better Survival in Endometrial Cancer CME/CE
News Author: Kate Johnson
CME Author: Charles P. Vega, MD
Endometrial cancer is associated with high rates of morbidity and mortality, and women with stage III or IV cancer, in which the tumor has extended outside of the uterus, are at particularly high risk for worse outcomes. These cases often involve multiple modalities to treat the cancer. A previous systematic review by Galaal and colleagues, which was published in the May 2014 issue of the Cochrane Database of Systematic Reviews, evaluated the efficacy of adjuvant chemotherapy among women with stage III or IV endometrial carcinoma.
The review focused on 4 randomized trials, which involved a total of 1269 women. Adjuvant chemotherapy was associated with significantly better results for overall survival and progression-free survival compared with adjuvant radiotherapy, regardless of stage III or IV cancer status. This benefit came at the price of higher rates of hematologic and neurologic adverse effects, and a fivefold increase in the rate of treatment discontinuation in comparing chemotherapy with radiotherapy. Limited data suggested that treatment with cisplatin/doxorubicin/paclitaxel yielded similar rates of progression-free survival as cisplatin/doxorubicin treatment, with more adverse effects associated with triple therapy.
Stage I endometrial cancer is usually treated with surgery, but can other treatments be effective for women who cannot undergo surgery because of medical reasons? The current study by Acharya and colleagues evaluates this issue.
Study Synopsis and Perspective
Women with inoperable early-stage endometrial cancer survive longer if their treatment includes brachytherapy rather than external beam radiotherapy alone, according to a new analysis of the National Cancer Institute's Surveillance, Epidemiology and End Results (SEER) database.
"Our results suggest that patients with medically inoperable stage I endometrial adenocarcinoma who are undergoing radiation should be treated with brachytherapy, if feasible," lead investigator Sahaja Acharya, MD, a resident physician in the Radiation Oncology Department of Washington University, in Saint Louis, Missouri, told Medscape Medical News.
The results were presented here at the European Society for Radiotherapy and Oncology (ESTRO) 3rd Forum.
Although early-stage endometrial cancer is most commonly treated with total hysterectomy and bilateral salpingo-oophorectomy, approximately 10% of stage I disease is inoperable, either because of comorbidities related to advanced age or those related to obesity, Dr Acharya explained.
Radiation is an alternative -- either external beam alone or brachytherapy (with or without external beam radiotherapy) -- but outcome data on these treatments are lacking, she said.
Better Outcomes Associated With Brachytherapy
The study included 460 patients from the SEER database who were diagnosed with stage I endometrioid adenocarcinoma and who underwent primary radiation between 1998 and 2011.
A total of 260 patients underwent external beam radiotherapy alone; 200 received brachytherapy with or without external beam radiotherapy. The percentage of patients undergoing brachytherapy ranged from 27% to 57% in any given year, with a slight downward trend during the study period, she noted.
After a mean follow-up of 35 months, the 3-year overall survival rate was 67% vs 40% favoring brachytherapy-treated patients (hazard ratio [HR], 0.67; P = .003).
Similarly, the 3-year cause-specific survival rate was 82% vs 74% favoring brachytherapy-treated patients (HR, 0.61; P = .022).
There was a statistically significant difference in age between the groups, with a median age of 76 years in the nonbrachytherapy group and 72 years in the brachytherapy group (P < .001). Because age and stage of disease are potentially confounding factors, the researchers performed an age-matched and stage-matched analysis in 304 patients. This showed that the benefit of brachytherapy persisted for overall survival (HR, 0.62; P = .001) and cause-specific survival (HR, 0.57; P = .022). "It is important to keep in mind that the improved outcomes are associated with brachytherapy, but no causal relationship can be made," said Dr Acharya.
It is possible that patients with more severe comorbidities were more likely to receive external beam radiotherapy and that patients in the external beam radiotherapy arm were treated with palliative rather than curative doses of radiation, but "the persistent difference in CSS [cause-specific survival] suggests that BT [brachytherapy] may effect survival even for those deemed too sick to benefit from it," she commented.
However, "since the majority of BT patients also received EBRT [external beam radiotherapy], no conclusion can be made with regard to the impact of BT alone," she emphasized.
Adding Fuel to the Fire
"This study adds fuel to the argument that brachytherapy is paramount for inoperable endometrial cancer patients, where the potential for cure and risk of undertreatment are present," Sushil Beriwal, MD, associate professor of radiation oncology at the University of Pittsburgh School of Medicine, in Pennsylvania, told Medscape Medical News when approached for comment.
Dr Beriwal recently published a similar study using the National Cancer Data Base "in which we were able to account for different external beam radiation doses," he said. "Even when stratifying by external beam doses into palliative and more aggressive regimens, patients that received external beam radiation alone, without brachytherapy, had a higher risk of overall death on multivariable analysis," he said.
Dr Beriwal said that together, the 2 studies highlight two points: "the risks of abandoning brachytherapy and misjudging a patient's risk of death from other causes. In our study, we demonstrated that patients who received palliative external beam radiation had a higher risk of death, arguing that physicians are underestimating their risk of cancer-related death. Secondly, brachytherapy utilization appears low in a population that is potentially curable with this technique. Brachytherapy enables delivery of a high local dose to the uterine cavity, which is where endometrial cancer originates, illustrating its unique value in controlling disease. It is difficult to replicate this dose delivery through external beam radiation without putting nearby organs at risk."
Additionally, Dr Beriwal noted his group's recently published study of patients with stage I to II inoperable endometrial cancer who were treated with newer techniques of brachytherapy. "Specifically, patients were treated using image-guided brachytherapy, enlisting the aid of MRI [magnetic resonance imaging]. In that series, we showed high rates of disease control and very low rates of toxicity with this approach. Although the entire uterus was prescribed to receive a modest dose of radiation, the uterine cavity received almost three times as much, highlighting again the value of brachytherapy for this patient population."
Dr Acharya and Dr Beriwal have disclosed no relevant financial relationships.
European Society for Radiotherapy and Oncology (ESTRO) 3rd Forum: Abstract OC-0277. Presented April 26, 2015.
lunes, 20 de julio de 2015
Carpe Diem
Carpe Diem
By Amir Steinberg, MD, FACP
June 25, 2015, Volume 6, Issue 11
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Related Links:
Patient Guides Available Through ASCO University Bookstore
Figures:
Amir Steinberg, MD, FACP
We are so preoccupied with what we are supposed to be doing, we often miss out on what we would most like to be doing. And if it is possible to pursue the things we love, get out of our rut, and seize the day, then maybe we should.
—Amir Steinberg, MD, FACP
My life as a cancer survivor and an oncologist has taught me the importance of living every day to the fullest.
Sometimes we all need a little reminding to appreciate life to the fullest. When I think of my former patient, Marc, that is what comes to mind. When I was a senior in high school, I was diagnosed with Hodgkin lymphoma. It was tough going, but I had a lot of support from my family, friends, teachers, and my doctor Fredrick B. Hagemeister, MD (Professor of Medicine in the Department of Lymphoma/Myeloma at the University of Texas MD Anderson Cancer Center in Houston). Dr. Hagemeister told me on my first day meeting him to “Live your life as normally as possible.” Since undergoing therapy over 20 years ago, I have tried to do just that.
Along the way, I used my life experience as a cancer survivor as motivation to pursue a career in medicine. Like Dr. Hagemeister, I wanted to be a lymphoma specialist, working at a large hospital, involved in research. And through the various stages of my medical training, hematology-oncology fellowship, and bone marrow transplantation fellowship, that continued to be my goal. However, sometimes when one is so goal oriented, life becomes all about pursuing the next step and not appreciating the present. Although it is important to think about the future and plan for that future, one can lose sight of living in the present day. My experience with Marc has helped remind me that today is equally important to focus on, as are the future tomorrows.
A Life Interrupted
I met Marc during my first year as an attending physician in Los Angeles. He was close to finishing his education at a local university with a degree in art. He had been studying abroad in Hong Kong, doing what he does best, living life to the fullest. While there, he developed chest discomfort. An x-ray of his chest was performed and showed a mediastinal mass. He returned to California, where a surgeon performed a biopsy and diagnosed him with T-cell lymphoblastic lymphoma.
He was soon referred to my team, and we took over his care. The therapy for his diagnosis would require several months of intense treatment, mainly inpatient. This precluded Marc from completing his last semester in college. I remember Marc often challenging me with complex questions about his therapy. He would ask me what he could and could not do physically, and he was most concerned about whether he could continue surfing, one of his great loves. Through it all, he tried living his life to the fullest, just as he had done prior to his diagnosis.
After undergoing 8 months of intense chemotherapy, and getting ready to start his 2-year maintenance chemotherapy, Marc began noticing blood in his urine and some discomfort on urination. A bladder mass was noted, and he was found to have recurrent lymphoma. As a result, he needed to undergo an allogeneic stem cell transplant. Although his sister’s stem cells were not a match for his immune system, fortunately, a near-match was found from the National Marrow Donor Program registry.
After his transplant, Marc went through several difficult months, but slowly his new immune system began doing its job, and he had no evidence of recurrent lymphoma. Marc began to feel well enough, and it became safe enough, to resume his education and complete his degree, and most importantly to Marc, to get back to the sport he loved, surfing, and living his life.
Throughout his illness and therapy, Marc had used art as an outlet to deal with his diagnosis and recovery. When I was leaving Los Angeles to take a position at Mount Sinai Hospital in New York, Marc presented me with a print he had created titled “Land of the Blind.” It depicts a wrinkled, worn face resembling Marc (though he indicated to me he did not consciously intend for there to be a resemblance), blind in one eye, wearing a crown with a “king” label, which now hangs on my office wall. It is an allusion to Erasmus’ phrase, “In the land of the blind, the one-eyed man is king.”
What was the meaning of this image to Marc? Clearly, the face (perhaps subconsciously his face) depicted in the print has been through a struggle and looks aged, thin, and weary from that struggle. And yet, in terms of the overarching message, perhaps Marc’s message was that until we have all been through such a difficult ordeal, we are blind to the meaning and the essence of life. And he is no longer completely blind to the essence and meaning of life because he’s been through a life-threatening situation, so he feels he can grasp life a bit more robustly than everyone else and put things into perspective a little bit better. And yet, even with this ordeal, no one truly knows the meaning of life, hence, continuing to be blind in one eye. At least that is my interpretation of his print.
Patient/Physician/Cancer Survivor Bond
A few months into my new job, I got an e-mail from Marc. He was driving across the country in a truck. During the drive, he explored the towns and cities he passed through and visited national parks and other tourist attractions he passed along the way. He would surf when he had the opportunity and then sleep in his truck to help maximize his finances for the trip. This was the essence of who Marc was and is. He knew that he had an opportunity to do this trip and that it would allow him to see America and enjoy surfing along the way. And he knew he should take advantage of this opportunity while he was healthy and could enjoy the journey without worrying what the next day would bring, truly following the Latin maxim carpe diem (seize the day). Doing things a little bit on the fly, doing them off the beaten path, and doing them because it was something new, something enjoyable, and something educational.
Marc arrived in the Big Apple and wanted to drop by for a visit. We hugged when we saw each other and then reminisced about his experiences as a cancer patient and about the experiences I had shared with him regarding my own journey as a cancer patient 20 years earlier. There was no doubt that we had formed a patient and physician bond, but I sensed we had also developed a bond as two former cancer patients, both diagnosed at a young age. The difference of those 20 years from where Marc was in his life and in the healing process and where I was in my life truly put my role as a physician into focus and showed me how I gave meaning to my own diagnosis by becoming an oncologist and helping provide Marc and other patients the opportunity to overcome their cancers and to live, long, healthy, productive lives.
I asked Marc what his future plans were and he replied “I’m not sure yet.” He did indicate, however, that he would seek out something he enjoyed doing. A few years later, I decided to e-mail Marc and see what he was up to. It turns out he had just returned from spending several months in Indonesia. He had worked at a local electronics shop in California to earn money to go on this trip. He spent his time surfing and experiencing the local cuisine and culture. I found it quite apropos for Marc that he would go on this trip. Once again, he was seizing the day. “Carpe diem!”
Living in the Present
Some may wonder why Marc doesn’t settle down, get a steady job, and start a family. Maybe someday he will do all those things, but right now his experience as a cancer survivor has given him different priorities and perspective on life. After all he has been through, he wants to take advantage of every day.
I understand and appreciate Marc’s “live for the day” philosophy. And I’ve learned important lessons from him. We get so caught up in our busy lives sometimes we lose sight of the essence, the spice, and the meaning of life. We are so preoccupied with what we are supposed to be doing, we often miss out on what we would most like to be doing. And if it is possible to pursue the things we love, get out of our rut, and seize the day, then maybe we should.
Marc is a young man, and if his cancer stays in remission, he has his whole life ahead of him to do what he is “supposed to do.” That being said, none of us knows when the next tragedy in life may strike, so why not enjoy life to the fullest right now, while we are still healthy and can pursue our dreams?
Talking with Marc and reflecting on my own life choices have prompted me to look inward as well and to try to get out of my comfort zone a bit. I’ve also learned to appreciate the little things in life every day, whether it is talking with my parents over the phone, reading to my son, taking my daughter to school, treating the family to ice cream, or having a thought-provoking discussion with my wife.
Like Marc, I’m seizing every day. Carpe diem! ■
Dr. Steinberg is Assistant Professor in Medicine in the Division of Hematology-Oncology at Mount Sinai Hospital in New York.
By Amir Steinberg, MD, FACP
June 25, 2015, Volume 6, Issue 11
advertisement
Related Links:
Patient Guides Available Through ASCO University Bookstore
Figures:
Amir Steinberg, MD, FACP
We are so preoccupied with what we are supposed to be doing, we often miss out on what we would most like to be doing. And if it is possible to pursue the things we love, get out of our rut, and seize the day, then maybe we should.
—Amir Steinberg, MD, FACP
My life as a cancer survivor and an oncologist has taught me the importance of living every day to the fullest.
Sometimes we all need a little reminding to appreciate life to the fullest. When I think of my former patient, Marc, that is what comes to mind. When I was a senior in high school, I was diagnosed with Hodgkin lymphoma. It was tough going, but I had a lot of support from my family, friends, teachers, and my doctor Fredrick B. Hagemeister, MD (Professor of Medicine in the Department of Lymphoma/Myeloma at the University of Texas MD Anderson Cancer Center in Houston). Dr. Hagemeister told me on my first day meeting him to “Live your life as normally as possible.” Since undergoing therapy over 20 years ago, I have tried to do just that.
Along the way, I used my life experience as a cancer survivor as motivation to pursue a career in medicine. Like Dr. Hagemeister, I wanted to be a lymphoma specialist, working at a large hospital, involved in research. And through the various stages of my medical training, hematology-oncology fellowship, and bone marrow transplantation fellowship, that continued to be my goal. However, sometimes when one is so goal oriented, life becomes all about pursuing the next step and not appreciating the present. Although it is important to think about the future and plan for that future, one can lose sight of living in the present day. My experience with Marc has helped remind me that today is equally important to focus on, as are the future tomorrows.
A Life Interrupted
I met Marc during my first year as an attending physician in Los Angeles. He was close to finishing his education at a local university with a degree in art. He had been studying abroad in Hong Kong, doing what he does best, living life to the fullest. While there, he developed chest discomfort. An x-ray of his chest was performed and showed a mediastinal mass. He returned to California, where a surgeon performed a biopsy and diagnosed him with T-cell lymphoblastic lymphoma.
He was soon referred to my team, and we took over his care. The therapy for his diagnosis would require several months of intense treatment, mainly inpatient. This precluded Marc from completing his last semester in college. I remember Marc often challenging me with complex questions about his therapy. He would ask me what he could and could not do physically, and he was most concerned about whether he could continue surfing, one of his great loves. Through it all, he tried living his life to the fullest, just as he had done prior to his diagnosis.
After undergoing 8 months of intense chemotherapy, and getting ready to start his 2-year maintenance chemotherapy, Marc began noticing blood in his urine and some discomfort on urination. A bladder mass was noted, and he was found to have recurrent lymphoma. As a result, he needed to undergo an allogeneic stem cell transplant. Although his sister’s stem cells were not a match for his immune system, fortunately, a near-match was found from the National Marrow Donor Program registry.
After his transplant, Marc went through several difficult months, but slowly his new immune system began doing its job, and he had no evidence of recurrent lymphoma. Marc began to feel well enough, and it became safe enough, to resume his education and complete his degree, and most importantly to Marc, to get back to the sport he loved, surfing, and living his life.
Throughout his illness and therapy, Marc had used art as an outlet to deal with his diagnosis and recovery. When I was leaving Los Angeles to take a position at Mount Sinai Hospital in New York, Marc presented me with a print he had created titled “Land of the Blind.” It depicts a wrinkled, worn face resembling Marc (though he indicated to me he did not consciously intend for there to be a resemblance), blind in one eye, wearing a crown with a “king” label, which now hangs on my office wall. It is an allusion to Erasmus’ phrase, “In the land of the blind, the one-eyed man is king.”
What was the meaning of this image to Marc? Clearly, the face (perhaps subconsciously his face) depicted in the print has been through a struggle and looks aged, thin, and weary from that struggle. And yet, in terms of the overarching message, perhaps Marc’s message was that until we have all been through such a difficult ordeal, we are blind to the meaning and the essence of life. And he is no longer completely blind to the essence and meaning of life because he’s been through a life-threatening situation, so he feels he can grasp life a bit more robustly than everyone else and put things into perspective a little bit better. And yet, even with this ordeal, no one truly knows the meaning of life, hence, continuing to be blind in one eye. At least that is my interpretation of his print.
Patient/Physician/Cancer Survivor Bond
A few months into my new job, I got an e-mail from Marc. He was driving across the country in a truck. During the drive, he explored the towns and cities he passed through and visited national parks and other tourist attractions he passed along the way. He would surf when he had the opportunity and then sleep in his truck to help maximize his finances for the trip. This was the essence of who Marc was and is. He knew that he had an opportunity to do this trip and that it would allow him to see America and enjoy surfing along the way. And he knew he should take advantage of this opportunity while he was healthy and could enjoy the journey without worrying what the next day would bring, truly following the Latin maxim carpe diem (seize the day). Doing things a little bit on the fly, doing them off the beaten path, and doing them because it was something new, something enjoyable, and something educational.
Marc arrived in the Big Apple and wanted to drop by for a visit. We hugged when we saw each other and then reminisced about his experiences as a cancer patient and about the experiences I had shared with him regarding my own journey as a cancer patient 20 years earlier. There was no doubt that we had formed a patient and physician bond, but I sensed we had also developed a bond as two former cancer patients, both diagnosed at a young age. The difference of those 20 years from where Marc was in his life and in the healing process and where I was in my life truly put my role as a physician into focus and showed me how I gave meaning to my own diagnosis by becoming an oncologist and helping provide Marc and other patients the opportunity to overcome their cancers and to live, long, healthy, productive lives.
I asked Marc what his future plans were and he replied “I’m not sure yet.” He did indicate, however, that he would seek out something he enjoyed doing. A few years later, I decided to e-mail Marc and see what he was up to. It turns out he had just returned from spending several months in Indonesia. He had worked at a local electronics shop in California to earn money to go on this trip. He spent his time surfing and experiencing the local cuisine and culture. I found it quite apropos for Marc that he would go on this trip. Once again, he was seizing the day. “Carpe diem!”
Living in the Present
Some may wonder why Marc doesn’t settle down, get a steady job, and start a family. Maybe someday he will do all those things, but right now his experience as a cancer survivor has given him different priorities and perspective on life. After all he has been through, he wants to take advantage of every day.
I understand and appreciate Marc’s “live for the day” philosophy. And I’ve learned important lessons from him. We get so caught up in our busy lives sometimes we lose sight of the essence, the spice, and the meaning of life. We are so preoccupied with what we are supposed to be doing, we often miss out on what we would most like to be doing. And if it is possible to pursue the things we love, get out of our rut, and seize the day, then maybe we should.
Marc is a young man, and if his cancer stays in remission, he has his whole life ahead of him to do what he is “supposed to do.” That being said, none of us knows when the next tragedy in life may strike, so why not enjoy life to the fullest right now, while we are still healthy and can pursue our dreams?
Talking with Marc and reflecting on my own life choices have prompted me to look inward as well and to try to get out of my comfort zone a bit. I’ve also learned to appreciate the little things in life every day, whether it is talking with my parents over the phone, reading to my son, taking my daughter to school, treating the family to ice cream, or having a thought-provoking discussion with my wife.
Like Marc, I’m seizing every day. Carpe diem! ■
Dr. Steinberg is Assistant Professor in Medicine in the Division of Hematology-Oncology at Mount Sinai Hospital in New York.
domingo, 19 de julio de 2015
ASCO: the Value of New Cancer Treatment Options
ASCO Publishes Conceptual Framework to Assess the Value of New Cancer Treatment Options
Framework to support shared decision-making between doctors and patients; ASCO solicits public comment
June 22, 2015
Contact:
Mary Rappaport
(571)-483-1374
mary.rappaport@asco.org
ALEXANDRIA, Va. – The American Society of Clinical Oncology (ASCO) today published an initial version of a conceptual framework for assessing the value of new cancer treatment options based on clinical benefit, side effects, and cost. The framework will serve as the basis for user-friendly, standardized tools that doctors can use with their patients to discuss the relative value of new cancer therapies compared with established treatments.
“Value and cost are among the biggest issues in healthcare today, but there are few tools to help doctors and patients objectively assess benefits, side effects and costs,” said ASCO President Julie M. Vose, MD, MBA, FASCO. “Our goal is to help oncologists and their patients weigh potential treatment options based on high-quality scientific evidence and a thoughtful assessment of each patient’s needs and goals. In publishing this initial version of the framework, just the beginning of the process, we hope to drive discussion and debate about a critically important issue.”
The ASCO Value Framework, published in the Journal of Clinical Oncology, was developed by ASCO’s Value in Cancer Care Task Force, with input from oncologists, patient advocates, representatives of the pharmaceutical and insurance industries, and others. ASCO is soliciting comments on the framework, which is available online at www.asco.org/value.
Cost an increasing burden for cancer patients
ASCO is developing the framework at a time when patients are increasingly affected by the costs of cancer care. Costs have risen sharply in recent years, and cancer drugs are a significant driver of these increases. Newly approved cancer drugs now cost an average of $10,000 per month, with some exceeding $30,000 per month. Many patients are feeling the impact because they pay a significant share of drug costs through health insurance deductibles, co-payments, and other out-of-pocket expenses.
“Cancer patients are increasingly burdened by the rising costs of care,” said Lowell E. Schnipper, MD, FASCO, Chair of ASCO’s Value in Cancer Care Task Force. “Even well-insured patients are often unprepared for the high out-of-pocket cost of some cancer therapies. Too often, that leads to severe financial strain and even bankruptcy.”
Studies have also shown that some cancer patients take less medication than prescribed, or avoid filling prescriptions altogether, because of concerns about cost.
Value framework draws on high-quality evidence
The ASCO Value Framework proposes a methodology to compare the relative clinical benefits, side effects, and costs of treatment regimens that have been tested head-to-head in randomized clinical trials.
Data on the clinical benefits and side effects of each regimen are used to calculate a combined “Net Health Benefit” score, or NHB. The NHB represents the added benefit that patients can expect to receive from the new therapy, versus the current standard of care. The NHB is calculated based on improvement in overall or progression-free survival, and on the number and severity of toxicities. For patients with advanced cancer, a higher NHB is awarded for regimens that also offer relief from cancer-related symptoms or allow patients a treatment-free period.
The framework relies on high-quality scientific evidence available from randomized clinical trials, including commonly-reported data such as clinical outcomes and toxicity. Other important measures, such as quality of life and patient-reported outcomes, are not used in the framework, because they are not reported consistently enough to be reliable.
The NHB is presented alongside the patient’s expected out-of-pocket costs for the regimens being compared, as well as the overall drug acquisition cost.
“It’s critical to distinguish between value and cost,” said Dr. Schnipper. “Sometimes the more valuable treatment will be the more expensive one and sometimes it won’t be. Ultimately, the definition of ‘value’ will be highly personalized for each patient, taking into account an individual’s own preferences and circumstances. For example, in the setting of advanced cancer, is length of life the most important goal or is quality of life? Is the proposed treatment affordable? That’s why we’re proposing to provide information on net health benefit and cost side-by-side.”
The framework is intended for doctors to use on an individual basis with their patients, and would not provide generalizable scores or rankings. Once the framework is finalized and adapted into a practical tool for clinical use, doctors would be able to adjust parameters based on an individual patient’s health needs, preferences, and financial situation—resulting in a personalized value assessment.
To help demonstrate the potential utility of the framework, the ASCO Task Force applied its methodology to four clinical scenarios: metastatic lung cancer; advanced multiple myeloma; metastatic prostate cancer; and adjuvant therapy for HER2-positive breast cancer. The results were striking: in some clinical scenarios, a newer, more expensive regimen had a much larger NHB than the previous standard. In other scenarios, the newer, more expensive regimen showed little or no net health benefit. These are sample scenarios only, and NHBs for the same regimen may vary in different types of cancer or treatment settings.
ASCO emphasizes that the proposed framework is intended to empower patients with clear information, and should not be used to limit patient choice. “This framework is about weighing the options, not limiting them,” said Dr. Vose. “It should not be used to replace physician judgment or patient preference.”
Seeking comment from all stakeholders
ASCO is soliciting feedback from all interested stakeholders on the framework’s methodology and applicability. Comments may be submitted through August 21, 2015 at www.asco.org/value.
Comments will inform the evolution of the value framework, which will be modified in response to feedback and updated as new data are developed about the utility and impact of new treatments in different clinical scenarios. Ultimately, ASCO plans to use the framework as the basis of physician-guided tools for day-to-day use in clinical settings. ASCO will move quickly to address input received, although the specific timeline for future steps is not yet determined.
About ASCO’s Value in Cancer Care Task Force
ASCO’s Value in Cancer Care Task Force is comprised of physicians, patient advocates, and representatives of the insurance and pharmaceutical industries. The Task Force was established in 2007 to educate oncologists about the importance of discussing costs associated with recommended treatments, empower patients to ask questions about the anticipated costs of their treatment options, identify the drivers of the rising costs of cancer care, and develop policy positions to promote access to the highest-quality care at the lowest cost. A list of Task Force members is available at www.asco.org/value.
Related products developed by ASCO include:
ASCO Task Force Guidance on the Cost of Cancer Care, 2009 for oncology professionals
Managing the Cost of Cancer Care for patients and families
Cancer.Net resources for patients about the costs of cancer care
ASCO has also participated in the “Choosing Wisely” initiative, sponsored by the American Board of Internal Medicine Foundation. As part of this effort, ASCO published two “Top Five” lists of opportunities to improve quality and value in cancer care by curbing use of common tests and treatments that are not supported by clinical evidence. ASCO is also advancing payment models that reward quality of care, rather than volume, and supporting quality efforts such as the Quality Oncology Practice Initiative (QOPI) and CancerLinQ, an initiative to harness big data analytics to improve cancer care.
###
About ASCO
Founded in 1964, the American Society of Clinical Oncology (ASCO) is the world’s leading professional organization representing physicians who care for people with cancer. With more than 35,000 members, ASCO is committed to improving cancer care through scientific meetings, educational programs and peer-reviewed journals. ASCO is supported by its affiliate organization, the Conquer Cancer Foundation, which funds ground-breaking research and programs that make a tangible difference in the lives of people with cancer. For ASCO information and resources, visit www.asco.org. Patient-oriented cancer information is available at www.cancer.net. For the latest cancer-related policy developments, please visit ascoaction.asco.org.
sábado, 18 de julio de 2015
Palbociclib's Role in Breast Cancer
Medscape Medical News > Oncology
Palbociclib's Role in Endocrine-Resistant Breast Cancer
Roxanne Nelson
July 15, 2015
Palbociclib (Ibrance, Pfizer), the first CDK4/6 inhibitor to be approved for the treatment of breast cancer, has been welcomed by experts for its role in improving outcomes in patients with endocrine-resistant breast cancer.
The drug should a significant improvement in progression-free survival (PFS) when it was added to fulvestrant (Faslodex, AstraZeneca) in the phase 3 PALOMA 3 trial, as reported recently by Medscape Medical News. The addition of palbociclib to fulvestrant increased median PFS to 9.2 months in patients with estrogen receptor (ER)–positive/HER2-negative endocrine-resistant breast cancer compared with 3.8 months in the placebo-fulvestrant group (P < .001). The overall survival data are still immature. The full results have now been published in print in the July 16 issue of the New England Journal of Medicine. But while these results are very promising, there are reasons to proceed with caution, experts comment in accompanying editorial. Editorialists Lisa A. Carey, MD, and Charles M. Perou, PhD, both from the University of North Carolina, Chapel Hill, point out that ER-positive breast cancer is biologically heterogeneous, and many patients do well long term, with minimal treatment, while using palbociclib adds considerable cost and toxicity to the treatment regimen. "Ideally, we should seek to identify patients with an excellent prognosis with endocrine therapy alone as well as predictive biomarkers for palbociclib to have a benefit," they write.
But given the lack of biomarker selectively for palbociclib, the population cannot be sufficiently narrowed to those who may derive the most benefit, Dr Carey told Medscape Medical News.
She noted that patients could be receiving this drug, at a very high cost and risk for toxicity, but not derive much benefit, "and this is a problem for us as a community."
"In the meantime palbociclib is a reasonable addition to letrozole [Femara, Novartis] in the first-line setting if tolerated, given the progression-free survival advantage and its approval," she said. "Long term we must identify those patients who will do well without it, and those who truly benefit, and we cannot do either at this time."
Study Details
Results from the PALOMA-3 study have been public since early June 2015, when they were presented at the 2015 annual meeting of the American Society of Clinical Oncology (ASCO) and simultaneously published online in the New England Journal of Medicine.
The improvement in PFS that was seen in this phase 3 study echoed the results seen in the earlier phase 2 PALOMA-1/TRIO-18 study, which were the basis for the accelerated approval of the drug, 2 months ahead of schedule.
For the PALOMA-3 study, Nicholas C. Turner, MD, PhD, from the Royal Marsden Hospital and Institute of Cancer Research, London, United Kingdom, and colleagues, enrolled 521 patients with advanced ER-positive, HER2-negative breast cancer that had relapsed or progressed during prior endocrine therapy.
Patients were randomly assigned 2:1 to receive palbociclib and fulvestrant or placebo and fulvestrant, and the primary end point was investigator-assessed progression-free survival. Secondary end points included overall survival, objective response, rate of clinical benefit, patient-reported outcomes, and safety.
The data cutoff date was December 5, 2014, for the interim analysis, and by then 195 events of disease progression or death had occurred (102 events in the palbociclib-fulvestrant group and 93 in the placebo-fulvestrant group). A total of 238 patients (68.6%) continue to receive treatment with palbociclib-fulvestrant and 75 patients (43.1%) with placebo-fulvestrant.
The trial met its primary end point at the interim analysis, showing a median PFS in favor of palbociclib: 9.2 months (95% confidence interval [CI], 7.5 months - not estimable) vs 3.8 months (95% CI, 3.5 - 5.5 months) with placebo-fulvestrant (hazard ratio for disease progression or death, 0.42; 95% CI, 0.32 - 0.56; P < .001). Rates of overall objective response were 10.4% for patients receiving palbociclib and 6.3% for the fulvestrant-only group (P = .16). The rate of clinical benefit (response or prolonged stable disease) at the interim analysis was 34.0% with palbociclib-fulvestrant and 19.0% with placebo-fulvestrant (P < .001). However, the authors note that at the time of the interim analysis, overall survival data are still immature. A total of 28 patients have died: 19 (5.5%) in the palbociclib-fulvestrant group and 9 (5.2%) in the placebo-fulvestrant group. The most common grade 3 or 4 adverse events observed in patients receiving palbociclib were neutropenia (62.0% vs 0.6% in the placebo-fulvestrant group), leukopenia (25.2% vs 0.6%), anemia (2.6% vs 1.7%), thrombocytopenia (2.3% vs 0%), and fatigue (2.0% vs 1.2%). In addition, the rate of febrile neutropenia was identical in both groups (0.6%) and the rate of discontinuation due to adverse events was 2.6% with palbociclib and 1.7% with placebo. At the ASCO annual meeting, experts applauded the drug as a welcome addition to the treatment armamentarium.
"It is exciting to have a novel, active, and well-tolerated biologic enter the treatment space," Erica Mayer, MD, assistant professor of medicine at Harvard Medical School, Boston, Massachusetts, told Medscape Medical News. "PALOMA 3 demonstrates efficacy in pretreated hormone receptor–positive breast cancer, suggesting the ability of CDK4/6 inhibition to overcome the challenge of endocrine resistance."
Conleth Murphy, MB, BCh, BAO, a medical oncologist at Bon Secours Hospital in Cork, Ireland, echoed those feelings. "This study is very important because it is the first phase 3 study to demonstrate efficacy in any setting for these agents…and represents the first phase 3 data supporting the use of this group of novel therapies in combination with endocrine therapy for women with hormone sensitive advanced breast cancer," said Dr Murphy.
The study was funded by Pfizer. Dr Turner has disclosed no relevant financial relationships, but several authors reported receiving fees from Pfizer, as well as other pharmaceutical companies; two authors are company employees. Dr Carey has disclosed no relevant financial relationships. Dr Perou reports receiving fees from Pfizer, G1 Therapeutics, Bioclassifier LLC, and GeneCentric Diagnostics and reports receiving royalties from a pending patent, licensed to Nanostring Technologies, related to gene expression profiles to predict breast cancer outcomes.
N Engl J Med. 2015;373:209-219, 273-274. Abstract Editorial
Palbociclib's Role in Endocrine-Resistant Breast Cancer
Roxanne Nelson
July 15, 2015
Palbociclib (Ibrance, Pfizer), the first CDK4/6 inhibitor to be approved for the treatment of breast cancer, has been welcomed by experts for its role in improving outcomes in patients with endocrine-resistant breast cancer.
The drug should a significant improvement in progression-free survival (PFS) when it was added to fulvestrant (Faslodex, AstraZeneca) in the phase 3 PALOMA 3 trial, as reported recently by Medscape Medical News. The addition of palbociclib to fulvestrant increased median PFS to 9.2 months in patients with estrogen receptor (ER)–positive/HER2-negative endocrine-resistant breast cancer compared with 3.8 months in the placebo-fulvestrant group (P < .001). The overall survival data are still immature. The full results have now been published in print in the July 16 issue of the New England Journal of Medicine. But while these results are very promising, there are reasons to proceed with caution, experts comment in accompanying editorial. Editorialists Lisa A. Carey, MD, and Charles M. Perou, PhD, both from the University of North Carolina, Chapel Hill, point out that ER-positive breast cancer is biologically heterogeneous, and many patients do well long term, with minimal treatment, while using palbociclib adds considerable cost and toxicity to the treatment regimen. "Ideally, we should seek to identify patients with an excellent prognosis with endocrine therapy alone as well as predictive biomarkers for palbociclib to have a benefit," they write.
But given the lack of biomarker selectively for palbociclib, the population cannot be sufficiently narrowed to those who may derive the most benefit, Dr Carey told Medscape Medical News.
She noted that patients could be receiving this drug, at a very high cost and risk for toxicity, but not derive much benefit, "and this is a problem for us as a community."
"In the meantime palbociclib is a reasonable addition to letrozole [Femara, Novartis] in the first-line setting if tolerated, given the progression-free survival advantage and its approval," she said. "Long term we must identify those patients who will do well without it, and those who truly benefit, and we cannot do either at this time."
Study Details
Results from the PALOMA-3 study have been public since early June 2015, when they were presented at the 2015 annual meeting of the American Society of Clinical Oncology (ASCO) and simultaneously published online in the New England Journal of Medicine.
The improvement in PFS that was seen in this phase 3 study echoed the results seen in the earlier phase 2 PALOMA-1/TRIO-18 study, which were the basis for the accelerated approval of the drug, 2 months ahead of schedule.
For the PALOMA-3 study, Nicholas C. Turner, MD, PhD, from the Royal Marsden Hospital and Institute of Cancer Research, London, United Kingdom, and colleagues, enrolled 521 patients with advanced ER-positive, HER2-negative breast cancer that had relapsed or progressed during prior endocrine therapy.
Patients were randomly assigned 2:1 to receive palbociclib and fulvestrant or placebo and fulvestrant, and the primary end point was investigator-assessed progression-free survival. Secondary end points included overall survival, objective response, rate of clinical benefit, patient-reported outcomes, and safety.
The data cutoff date was December 5, 2014, for the interim analysis, and by then 195 events of disease progression or death had occurred (102 events in the palbociclib-fulvestrant group and 93 in the placebo-fulvestrant group). A total of 238 patients (68.6%) continue to receive treatment with palbociclib-fulvestrant and 75 patients (43.1%) with placebo-fulvestrant.
The trial met its primary end point at the interim analysis, showing a median PFS in favor of palbociclib: 9.2 months (95% confidence interval [CI], 7.5 months - not estimable) vs 3.8 months (95% CI, 3.5 - 5.5 months) with placebo-fulvestrant (hazard ratio for disease progression or death, 0.42; 95% CI, 0.32 - 0.56; P < .001). Rates of overall objective response were 10.4% for patients receiving palbociclib and 6.3% for the fulvestrant-only group (P = .16). The rate of clinical benefit (response or prolonged stable disease) at the interim analysis was 34.0% with palbociclib-fulvestrant and 19.0% with placebo-fulvestrant (P < .001). However, the authors note that at the time of the interim analysis, overall survival data are still immature. A total of 28 patients have died: 19 (5.5%) in the palbociclib-fulvestrant group and 9 (5.2%) in the placebo-fulvestrant group. The most common grade 3 or 4 adverse events observed in patients receiving palbociclib were neutropenia (62.0% vs 0.6% in the placebo-fulvestrant group), leukopenia (25.2% vs 0.6%), anemia (2.6% vs 1.7%), thrombocytopenia (2.3% vs 0%), and fatigue (2.0% vs 1.2%). In addition, the rate of febrile neutropenia was identical in both groups (0.6%) and the rate of discontinuation due to adverse events was 2.6% with palbociclib and 1.7% with placebo. At the ASCO annual meeting, experts applauded the drug as a welcome addition to the treatment armamentarium.
"It is exciting to have a novel, active, and well-tolerated biologic enter the treatment space," Erica Mayer, MD, assistant professor of medicine at Harvard Medical School, Boston, Massachusetts, told Medscape Medical News. "PALOMA 3 demonstrates efficacy in pretreated hormone receptor–positive breast cancer, suggesting the ability of CDK4/6 inhibition to overcome the challenge of endocrine resistance."
Conleth Murphy, MB, BCh, BAO, a medical oncologist at Bon Secours Hospital in Cork, Ireland, echoed those feelings. "This study is very important because it is the first phase 3 study to demonstrate efficacy in any setting for these agents…and represents the first phase 3 data supporting the use of this group of novel therapies in combination with endocrine therapy for women with hormone sensitive advanced breast cancer," said Dr Murphy.
The study was funded by Pfizer. Dr Turner has disclosed no relevant financial relationships, but several authors reported receiving fees from Pfizer, as well as other pharmaceutical companies; two authors are company employees. Dr Carey has disclosed no relevant financial relationships. Dr Perou reports receiving fees from Pfizer, G1 Therapeutics, Bioclassifier LLC, and GeneCentric Diagnostics and reports receiving royalties from a pending patent, licensed to Nanostring Technologies, related to gene expression profiles to predict breast cancer outcomes.
N Engl J Med. 2015;373:209-219, 273-274. Abstract Editorial
Diet and Prostate Cancer
Medscape Urology > Chodak on Urology
COMMENTARY
Which Diet Confers the Most Benefit in Prostate Cancer?
Gerald Chodak, MD
Disclosures July 02, 2015
Hello. I am Dr Gerald Chodak for Medscape. Today I want to talk about a prospective study that looked at the impact of diet on men with prostate cancer.
Meng Yang and colleagues[1] assessed the dietary patterns of 926 men who participated in the Physicians' Health Study. The men were sent questionnaires about their dietary intake during the 5 years after their cancer diagnosis. They were then followed for 10 more years.
The study defined two diets: a Western diet and a healthy diet. The men on a Western diet ate processed and red meats, high-fat dairy foods, and refined grains. Fruit was not part of the Western diet, but sweets, cakes, candy, potatoes, and eggs were included. In the healthy-diet group, the men ate fish, fresh fruit and vegetables, whole grains, and a minimum or a reduced amount of food from the Western diet.
When divided into quartiles, the men who had the highest intake of a Western dietary pattern had higher overall risks for mortality and prostate cancer mortality. Conversely, the men in the highest quartile for the healthy diet had the lowest overall mortality.
The study did not find a significant correlation between the healthy diet and prostate cancer mortality, primarily because there weren't enough prostate cancer deaths in that group.
The bottom line from this analysis was that a Western diet was not good for overall survival or prostate cancer survival.
The researchers were able to identify what they thought were the most important products in the diet. For men eating the healthy diet, oil and vinegar used in salad dressings were identified as conferring a benefit.
Other studies have looked at the benefits of oil and vinegar and found that the Mediterranean diet, with significant olive oil intake,[2] improves overall health and reduces mortality.Whether that will help men who have a diagnosis of prostate cancer is less clear.
It is interesting, however, that most of the men diagnosed with localized prostate cancer don't actually die from prostate cancer. They die from other causes.
For men who want to improve their overall survival, these guidelines suggest avoiding the Western diet. Whether a Mediterranean diet will lower their risk of dying from prostate cancer remains unclear. There is considerable uncertainty even in the literature.
There are some shortcomings to the study. For example, mainly white male physicians were studied. It is unclear how applicable this study would be to other races or socioeconomic groups.
For now, this adds to information suggesting that the typical Western diet is not good for overall health, and not good for men with a diagnosis of localized prostate cancer because it appears to increase the mortality risk.
Whether switching diets reduces the risk of dying from prostate cancer is unclear, but eating a healthy diet will certainly help reduce the risk of dying from other causes.
I look forward to your comments. Thank you.
COMMENTARY
Which Diet Confers the Most Benefit in Prostate Cancer?
Gerald Chodak, MD
Disclosures July 02, 2015
Hello. I am Dr Gerald Chodak for Medscape. Today I want to talk about a prospective study that looked at the impact of diet on men with prostate cancer.
Meng Yang and colleagues[1] assessed the dietary patterns of 926 men who participated in the Physicians' Health Study. The men were sent questionnaires about their dietary intake during the 5 years after their cancer diagnosis. They were then followed for 10 more years.
The study defined two diets: a Western diet and a healthy diet. The men on a Western diet ate processed and red meats, high-fat dairy foods, and refined grains. Fruit was not part of the Western diet, but sweets, cakes, candy, potatoes, and eggs were included. In the healthy-diet group, the men ate fish, fresh fruit and vegetables, whole grains, and a minimum or a reduced amount of food from the Western diet.
When divided into quartiles, the men who had the highest intake of a Western dietary pattern had higher overall risks for mortality and prostate cancer mortality. Conversely, the men in the highest quartile for the healthy diet had the lowest overall mortality.
The study did not find a significant correlation between the healthy diet and prostate cancer mortality, primarily because there weren't enough prostate cancer deaths in that group.
The bottom line from this analysis was that a Western diet was not good for overall survival or prostate cancer survival.
The researchers were able to identify what they thought were the most important products in the diet. For men eating the healthy diet, oil and vinegar used in salad dressings were identified as conferring a benefit.
Other studies have looked at the benefits of oil and vinegar and found that the Mediterranean diet, with significant olive oil intake,[2] improves overall health and reduces mortality.Whether that will help men who have a diagnosis of prostate cancer is less clear.
It is interesting, however, that most of the men diagnosed with localized prostate cancer don't actually die from prostate cancer. They die from other causes.
For men who want to improve their overall survival, these guidelines suggest avoiding the Western diet. Whether a Mediterranean diet will lower their risk of dying from prostate cancer remains unclear. There is considerable uncertainty even in the literature.
There are some shortcomings to the study. For example, mainly white male physicians were studied. It is unclear how applicable this study would be to other races or socioeconomic groups.
For now, this adds to information suggesting that the typical Western diet is not good for overall health, and not good for men with a diagnosis of localized prostate cancer because it appears to increase the mortality risk.
Whether switching diets reduces the risk of dying from prostate cancer is unclear, but eating a healthy diet will certainly help reduce the risk of dying from other causes.
I look forward to your comments. Thank you.
miércoles, 15 de julio de 2015
Prostate Cancer Management in US
Medscape Medical News > Oncology
'Genuine Change' in US Prostate Cancer Management
Nick Mulcahy
July 07, 2015
At long last, changes are being seen in the management of prostate cancer in the United States. Disturbing practices appear to be markedly on the wane, especially in recent years, according to new research.
In the years 2010-2013, the use of active surveillance for low-risk disease "increased sharply" to 40% of all cases, say investigators. The rate had languished at only about 10% in the preceding 20 years.
At the same time, use of androgen deprivation as a monotherapy "decreased sharply," they note, down to only 3.8% of intermediate-risk and 24% of high-risk prostate cancer cases. These percentages represent drops of about one third and one half from earlier periods.
Both trends are desirable because they represent strategies to avoid overtreatment and undertreatment, respectively.
Notably, there have been financial incentives to both do too much and too little, depending on the patient's risk and reimbursement schemes.
"The magnitude and speed of the changes suggest a genuine change in the management of patients with prostate cancer in the United States," write Matthew Cooperberg, MD, MPH, and Peter Carroll, MD, MPH, of the Helen Diller Family Comprehensive Cancer Center at the University of California, San Francisco (UCSF).
The magnitude and speed of the changes suggest a genuine change. Dr Matthew Cooperberg
The pair report on the management of prostate cancer from 1990-2013 in a research letter published online July 7 in JAMA.
The findings on active surveillance are important, in part because they come largely from community-based practice, say the authors.
The safety and efficacy of active surveillance have been established almost entirely in the setting of academic centers.
The UCSF duo used the national registry known as CaPSURE (Cancer of the Prostate Strategic Urologic Research Endeavor), which consists of 45 urology practices in 28 states. All but three practices are community based, and the practices are both large and small in size.
All of the 10,472 men included in the study had localized disease (cT3aN0M0 or lower) and were managed with either prostatectomy, radiation, androgen deprivation monotherapy, or active surveillance/watchful waiting.
The men had either low-, intermediate-, or high-risk disease (determined on the basis of CAPRA scores).
The authors found that surveillance use for low-risk disease (CAPRA 0-2) "remained low" from 1990-2009 (ranging from 6.7% to 14.3%) but then dramatically spiked to 40.4% in 2010-2013 (P < .001 for trend).
During this time frame, the inappropriate use of androgen deprivation monotherapy dropped in men with intermediate-risk (from 9.7% in 1990 to 3.8% in 2010-2013) and high-risk disease (from 29.8% in 1990 to 50% in 2005-2009 and then back down to 24% in 2010-2013).
The authors explain that potentially curative local treatment should be used in these men at higher risk, rather than a systemic monotherapy. But, as widely reported, there were ongoing financial incentives for clinicians to prescribe ADT before Medicare reform occurred in 2005.
The news about active surveillance is not all that new.
At this year's annual meeting of the American Urological Association (AUA), Dr Cooperberg reported data from this very same CaPSURE registry, but they were sliced up differently.
In the United States from 2008-2013, the primary treatment for 38.4% of men with low-risk tumors was watchful waiting or active surveillance, he told the meeting.
"It is reassuring to see this evidence that active surveillance is finally being embraced in the United States," said Stacy Loeb, MD, from New York University, in New York City, who was not involved in this research and was asked for comment on the new article.
She also said that the CaPSURE data agree with other recent American registry studies, including one from the state of Michigan that reported that 49% of eligible men received active surveillance.
But Dr Loeb also told Medscape Medical News that "rates of active surveillance [in the United States] have historically been lower than observed in other countries."
In Sweden, for example, 2013 figures indicate that active surveillance is used to manage 78% of men with very-low-risk disease and 59% of men with low-risk disease, as reported earlier this year.
Nevertheless, the practice of active surveillance is increasing on both continents. "The era of active surveillance has arrived," declared Dr Loeb at the AUA meeting in May.
Why did the dramatic upturn in surveillance happen in 2010-2013?
One of the landmark events in this time frame occurred in 2010, when the National Comprehensive Cancer Network's practice guidelines for prostate cancer recommended, for the first time, the use of active surveillance as the sole initial treatment — not just an option — for many men with prostate cancer, as reported by Medscape Medical News.
The data in the new study are different for men aged 75 years and older.
The older men have seen, during the study period, an increase in the use of active surveillance. The rate in 2010-2013 was 76.2%. However, for this same recent period, there was also an increase in the use of surgery in this age group with low-risk cancer (to 9.5%) and with intermediate-risk cancer (to 15%).
CaPSURE is currently funded by the US Department of Defense and the University of California, San Francisco. Dr Cooperberg reports financial ties with both pharmaceutical and genetic testing companies involved in either prostate cancer treatment or evaluation.
JAMA. Published online July 7, 2015. Abstract
'Genuine Change' in US Prostate Cancer Management
Nick Mulcahy
July 07, 2015
At long last, changes are being seen in the management of prostate cancer in the United States. Disturbing practices appear to be markedly on the wane, especially in recent years, according to new research.
In the years 2010-2013, the use of active surveillance for low-risk disease "increased sharply" to 40% of all cases, say investigators. The rate had languished at only about 10% in the preceding 20 years.
At the same time, use of androgen deprivation as a monotherapy "decreased sharply," they note, down to only 3.8% of intermediate-risk and 24% of high-risk prostate cancer cases. These percentages represent drops of about one third and one half from earlier periods.
Both trends are desirable because they represent strategies to avoid overtreatment and undertreatment, respectively.
Notably, there have been financial incentives to both do too much and too little, depending on the patient's risk and reimbursement schemes.
"The magnitude and speed of the changes suggest a genuine change in the management of patients with prostate cancer in the United States," write Matthew Cooperberg, MD, MPH, and Peter Carroll, MD, MPH, of the Helen Diller Family Comprehensive Cancer Center at the University of California, San Francisco (UCSF).
The magnitude and speed of the changes suggest a genuine change. Dr Matthew Cooperberg
The pair report on the management of prostate cancer from 1990-2013 in a research letter published online July 7 in JAMA.
The findings on active surveillance are important, in part because they come largely from community-based practice, say the authors.
The safety and efficacy of active surveillance have been established almost entirely in the setting of academic centers.
The UCSF duo used the national registry known as CaPSURE (Cancer of the Prostate Strategic Urologic Research Endeavor), which consists of 45 urology practices in 28 states. All but three practices are community based, and the practices are both large and small in size.
All of the 10,472 men included in the study had localized disease (cT3aN0M0 or lower) and were managed with either prostatectomy, radiation, androgen deprivation monotherapy, or active surveillance/watchful waiting.
The men had either low-, intermediate-, or high-risk disease (determined on the basis of CAPRA scores).
The authors found that surveillance use for low-risk disease (CAPRA 0-2) "remained low" from 1990-2009 (ranging from 6.7% to 14.3%) but then dramatically spiked to 40.4% in 2010-2013 (P < .001 for trend).
During this time frame, the inappropriate use of androgen deprivation monotherapy dropped in men with intermediate-risk (from 9.7% in 1990 to 3.8% in 2010-2013) and high-risk disease (from 29.8% in 1990 to 50% in 2005-2009 and then back down to 24% in 2010-2013).
The authors explain that potentially curative local treatment should be used in these men at higher risk, rather than a systemic monotherapy. But, as widely reported, there were ongoing financial incentives for clinicians to prescribe ADT before Medicare reform occurred in 2005.
The news about active surveillance is not all that new.
At this year's annual meeting of the American Urological Association (AUA), Dr Cooperberg reported data from this very same CaPSURE registry, but they were sliced up differently.
In the United States from 2008-2013, the primary treatment for 38.4% of men with low-risk tumors was watchful waiting or active surveillance, he told the meeting.
"It is reassuring to see this evidence that active surveillance is finally being embraced in the United States," said Stacy Loeb, MD, from New York University, in New York City, who was not involved in this research and was asked for comment on the new article.
She also said that the CaPSURE data agree with other recent American registry studies, including one from the state of Michigan that reported that 49% of eligible men received active surveillance.
But Dr Loeb also told Medscape Medical News that "rates of active surveillance [in the United States] have historically been lower than observed in other countries."
In Sweden, for example, 2013 figures indicate that active surveillance is used to manage 78% of men with very-low-risk disease and 59% of men with low-risk disease, as reported earlier this year.
Nevertheless, the practice of active surveillance is increasing on both continents. "The era of active surveillance has arrived," declared Dr Loeb at the AUA meeting in May.
Why did the dramatic upturn in surveillance happen in 2010-2013?
One of the landmark events in this time frame occurred in 2010, when the National Comprehensive Cancer Network's practice guidelines for prostate cancer recommended, for the first time, the use of active surveillance as the sole initial treatment — not just an option — for many men with prostate cancer, as reported by Medscape Medical News.
The data in the new study are different for men aged 75 years and older.
The older men have seen, during the study period, an increase in the use of active surveillance. The rate in 2010-2013 was 76.2%. However, for this same recent period, there was also an increase in the use of surgery in this age group with low-risk cancer (to 9.5%) and with intermediate-risk cancer (to 15%).
CaPSURE is currently funded by the US Department of Defense and the University of California, San Francisco. Dr Cooperberg reports financial ties with both pharmaceutical and genetic testing companies involved in either prostate cancer treatment or evaluation.
JAMA. Published online July 7, 2015. Abstract
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