MSI, MMRD Biomarkers Might Guide Gastro-Oesophageal Cancer Periop Chemotherapy Use
Perioperative chemotherapy benefit in gastro-oesophageal cancer may vary with microsatellite instability and mismatch repair deficiency status
Date: 27 Feb 2017
Author: By Lynda Williams, Senior medwireNews Reporter
Topic: Anti-Cancer Agents & Biologic Therapy / Oesophageal Cancer / Gastric Cancer / Translational Research / Surgery and/or Radiotherapy of Cancer
medwireNews: Examining for Microsatellite instability (MSI) and Mismatch repair deficiency (MMRD) could help identify which gastro-oesophageal cancer patients will benefit from perioperative chemotherapy, research suggests.
“Because MSI or MMRD tumors comprise up to 10% to 20% of stomach cancers in some series, this finding has the potential to affect large numbers of patients”, the study authors believe.
The secondary post hoc analysis of the MAGIC (Medical Research Council Adjuvant Gastric Infusional Chemotherapy) trial included MSI data for 303 participants who were treated for operable gastro-oesophageal cancer with surgery alone or alongside epirubicin, cisplatin and fluorouracil chemotherapy.
The original trial findings showed that 5-year overall survival (OS) was significantly longer in the patients given combined therapy, explain David Cunningham, from the Royal Marsden Hospital in London, UK, and co-authors in JAMA Oncology.
In all, 283 patients had tumours which showed microsatellite stability or low MSI, while 20 patients had high MSI, they report. And for the 254 patients with MMR results available for the proteins mutL homologue 1, mutS homologue 2, mutS homologue 6 and PMS1 homologue 2, concordance between high MSI and MMRD status was 97.6%.
Among the patients treated with surgery alone, median OS was not reached in the patients with high MSI or MMRD versus a median of 20.5 months for the patients who had neither Biomarker, giving a nonsignificant hazard ratio (HR) of 0.42.
For patients who had received perioperative chemotherapy, however, median OS was significantly shorter for those with high MSI or MMRD than those without, at 9.6 versus 19.5 months and a HR of 2.18.
“If validated, this finding has the potential to improve patient selection for perioperative chemotherapy and spare a significant proportion of patients with gastric cancer unnecessary treatment”, the MAGIC investigators say.
“We do not believe that these data justify a change in clinical practice; however, we recommend prospective trial validation to ascertain the optimal perioperative treatment for patients with [high MSI] gastric cancer.”
And they add: “In light of the remarkable success of anti–programmed cell death protein 1 therapies in MMRD colorectal cancer, alternative treatment strategies could be reasonably investigated for these patients.”
Reference
Symth EC, Wotherspoon A, Peckitt C, et al. Mismatch repair deficiency, microsatellite instability, and survival. An exploratory analysis of the Medical Research Council Adjuvant Gastric Infusional Chemotherapy (MAGIC) trial. JAMA Oncol 2017; Advance online publication 23 February. doi:10.1001/jamaoncol.2016.6762
sábado, 11 de marzo de 2017
Cancer-Related Fatigue
Exercise, Psychological Interventions Beat Pharma Options For Cancer-Related Fatigue
Meta-analysis points to a strategy of exercise and psychological therapy rather than pharmaceutical treatment for patients with cancer-related fatigue
Date: 07 Mar 2017
Author: By Lynda Williams, Senior medwireNews Reporter
Topic: Supportive Care
medwireNews: Clinicians should treat cancer-related fatigue (CRF) with exercise-based and/or psychological interventions, indicates a meta-analysis published in JAMA Oncology.
The data from 11,525 participants of 113 studies showed that these options had a stronger impact on CRF than did pharmaceutical agents, such as paroxetine hydrochloride or modafinil, say Karen Mustian, from the University of Rochester Medical Center in New York, USA, and co-authors.
The randomised controlled studies included in the meta-analysis were judged to be of good quality and to have sufficient data on fatigue to allow determination of a mean weighted effect size (WES) for CRF severity, the researchers explain.
Almost half (46.9%) of the studies were conducted in breast cancer patients and the remainder in those with other tumour types, with 44.2% including participants with nonmetastatic cancer, 9.7% only those with metastases and 29.2% with both populations.
Both exercise interventions and psychological interventions, and combined exercise and psychological interventions, impacted on CRF during and after cancer treatment, with significant moderate effects of 0.30, 0.27 and 0.26, respectively. By contrast, pharmacological interventions had a “significant but very small” WES of 0.09.
The authors believe their study is the first to indicate that the efficacy of CRF treatment is linked to eight different factors, with WES ranging from –0.91 to 0.99.
Specifically, CRF reductions were greatest in patients with early-stage cancer, those who had completed their primary treatment, and in participants given cognitive behavioural therapy types of psychological intervention. CRF interventions that were given to groups of patients and in person were also particularly effective, as were those measured using the Piper Fatigue Scale and where the control condition was standard care.
“However, exercise and psychological interventions produced significant improvements in CRF, even when a rigorous specific-component (behavioural placebo) control comparison was used”, the researchers say.
Likewise, the team suggests that their study has shown for the first time that CRF efficacy is not related to patient age, cancer type or whether the exercise recommended was aerobic, anaerobic resistance or a combination, but might be influenced by the timing of CRF intervention.
“For example, exercise may be the most effective treatment for patients receiving primary treatment, whereas psychological and exercise plus psychological interventions may be most effective for survivors who have completed primary treatment”, write Karen Mustian et al.
While recommending more phase III research into the use of exercise-based and psychological interventions, the researchers conclude: “Clinicians should prescribe exercise and psychological interventions as first-line therapy for patients experiencing CRF.”
Reference
Mustian KM, Alfano CM, Heckler C, et al. Comparison of pharmaceutical, psychological and exercise treatments for cancer-related fatigue. A meta-analysis. JAMA Oncol; Advance online publication 2 March 2017. doi:10.1001/jamaoncol.2016.6914
Meta-analysis points to a strategy of exercise and psychological therapy rather than pharmaceutical treatment for patients with cancer-related fatigue
Date: 07 Mar 2017
Author: By Lynda Williams, Senior medwireNews Reporter
Topic: Supportive Care
medwireNews: Clinicians should treat cancer-related fatigue (CRF) with exercise-based and/or psychological interventions, indicates a meta-analysis published in JAMA Oncology.
The data from 11,525 participants of 113 studies showed that these options had a stronger impact on CRF than did pharmaceutical agents, such as paroxetine hydrochloride or modafinil, say Karen Mustian, from the University of Rochester Medical Center in New York, USA, and co-authors.
The randomised controlled studies included in the meta-analysis were judged to be of good quality and to have sufficient data on fatigue to allow determination of a mean weighted effect size (WES) for CRF severity, the researchers explain.
Almost half (46.9%) of the studies were conducted in breast cancer patients and the remainder in those with other tumour types, with 44.2% including participants with nonmetastatic cancer, 9.7% only those with metastases and 29.2% with both populations.
Both exercise interventions and psychological interventions, and combined exercise and psychological interventions, impacted on CRF during and after cancer treatment, with significant moderate effects of 0.30, 0.27 and 0.26, respectively. By contrast, pharmacological interventions had a “significant but very small” WES of 0.09.
The authors believe their study is the first to indicate that the efficacy of CRF treatment is linked to eight different factors, with WES ranging from –0.91 to 0.99.
Specifically, CRF reductions were greatest in patients with early-stage cancer, those who had completed their primary treatment, and in participants given cognitive behavioural therapy types of psychological intervention. CRF interventions that were given to groups of patients and in person were also particularly effective, as were those measured using the Piper Fatigue Scale and where the control condition was standard care.
“However, exercise and psychological interventions produced significant improvements in CRF, even when a rigorous specific-component (behavioural placebo) control comparison was used”, the researchers say.
Likewise, the team suggests that their study has shown for the first time that CRF efficacy is not related to patient age, cancer type or whether the exercise recommended was aerobic, anaerobic resistance or a combination, but might be influenced by the timing of CRF intervention.
“For example, exercise may be the most effective treatment for patients receiving primary treatment, whereas psychological and exercise plus psychological interventions may be most effective for survivors who have completed primary treatment”, write Karen Mustian et al.
While recommending more phase III research into the use of exercise-based and psychological interventions, the researchers conclude: “Clinicians should prescribe exercise and psychological interventions as first-line therapy for patients experiencing CRF.”
Reference
Mustian KM, Alfano CM, Heckler C, et al. Comparison of pharmaceutical, psychological and exercise treatments for cancer-related fatigue. A meta-analysis. JAMA Oncol; Advance online publication 2 March 2017. doi:10.1001/jamaoncol.2016.6914
miércoles, 1 de marzo de 2017
Utidelone Plus Capecitabine ‘Promising’ For Refractory Metastatic Breast Cancer
Utidelone Plus Capecitabine ‘Promising’ For Refractory Metastatic Breast Cancer
Combining an epothilone analogue with capecitabine may be effective against anthracycline- and taxane-refractory metastatic breast cancer
Date: 16 Feb 2017
Author: By Lynda Williams, Senior medwireNews Reporter
Topic: Anti-Cancer Agents & Biologic Therapy / Breast Cancer, Metastatic
medwireNews: Adding the epothilone analogue utidelone to capecitabine extends progression-free survival (PFS) in women with metastatic breast cancer refractory to both anthracycline- and taxane-based chemotherapy, suggest phase III trial results from China.
Reporting that the combination treatment has a “manageable safety profile”, the investigators believe their findings “support the favourable benefit–risk profile of this regimen and offer a new potential option for patients with heavily pretreated metastatic breast cancer.”
Median PFS was determined by independent radiology review to be 8.44 months for the 270 patients who were randomly assigned to receive 21-day cycles of chemotherapy consisting of utidelone 30 mg/m2 per day on days 1–15 plus capecitabine 1000 mg/m2 twice daily on days 1–14.
This compared with a median PFS of 4.27 months for the 135 patients using capecitabine only, giving a significant hazard ratio (HR) of 0.46.
“In our study, utidelone-related toxicities were generally mild to moderate and considered clinically manageable”, report Binghe Xhu, from National Cancer Venter/Cancer Hospital in Beijing, China, and co-workers.
Peripheral neuropathy was the most common grade 3 adverse effect in patients given utidelone plus capecitabine, affecting 22%. Noting that the patients had all previously used taxanes and other agents associated with peripheral neuropathy, the team hypothesizes that “[t]hese previous regimens could have sensitised patients to utidelone-induced peripheral neuropathy.”
Palmar–plantar erythrodysaesthesia was the most common grade 3 event common in patients given capecitabine alone (8%) and the third most common grade 3 event for those given combination treatment (7%), after neutropenia (12%).
There were sixteen serious adverse events in the combination treatment arm and 14 in the capecitabine only arm, with diarrhoea reported in three and two patients, respectively.
Further analysis indicated that patients given combination treatment were significantly more likely to have an objective response than those treated with capecitabine monotherapy (40.4 vs 21.5%) and to derive clinical benefit from treatment (53.9 vs 26.0%), defined as a complete or partial response or stable disease for at least 6 months.
The trial investigators explain in The Lancet Oncology that overall survival (OS) data are immature but that at cutoff utidelone plus capecitabine appeared to offer longer OS, at a median of 16.13 months versus 12.78 months with capecitabine monotherapy, and a significant HR of 0.63.
However, Xavier Pivot, from University Hospital J Minjoz in Besançon, France, cautions in an accompanying article that “[a]lthough encouraging, mature overall survival data are needed before making any decision for regulatory approval of utidelone.”
He also notes that a quarter of the patients in the trial had HER2-positive breast cancer and that subsequent targeted treatment may affect the final OS analysis.
“In the future, large randomised studies in metastatic breast cancer should include a statistical plan that is able to provide conclusions about overall survival and the population should be restricted to a group of patients that unquestionably require chemotherapy alone”, the commentator recommends.
References
Zhang P, Sun T, Zhang Q, et al. Utidelone plus capecitabine versus capecitabine alone for heavily pretreated metastatic breast cancer refractory to anthracylines and taxanes: a multicentre, open-label, superiority, phase 3, randomised controlled trial. Lancet Oncol; Advance online publication 10 February 2017. DOI: http://dx.doi.org/10.1016/S1470-2045(17)30088-8
Piovot X. Classic cytotoxic drugs: a narrow path for regulatory approval. Lancet Oncol; Advance online publication 10 February 2017. DOI: http://dx.doi.org/10.1016/S1470-2045(17)30089-X
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