Medscape
News > Oncology
Cutting Cancer Drug Costs: No Pain, No Gain
Roxanne Nelson, BSN, RN
February 16, 2016
Over the past decade, as the price of cancer drugs has skyrocketed, many in the oncology community have asked this question: Is it possible to create a public policy that will harness these costs and cut out-of-pocket expenses for patients?
It is possible, but not without making significant tradeoffs that could reduce access to some oncology drugs, according to Scott Ramsey, MD, PhD, director of the Hutchinson Institute for Cancer Outcomes Research in Seattle, and colleagues.
Whether or not "society will accept that pain for the gain of a more equitable and sustainable cancer drug market remains to be seen," they write in an editorial published online February 11 in JAMA Oncology.
They propose three interventions that could help relieve the financial distress many cancer patients experience.
Unlike many calls for reform, which are directed toward the pharmaceutical industry, their proposals are focused primarily on health insurance.
First, they explain, both public and private health insurers must have the ability to negotiate prices with manufacturers.
Second, insurers need to be able to withhold products from their formularies if drug prices do not represent good value.
And third, there needs to be greater transparency of cancer drug pricing and better information about treatment choices.
I don't see other viable options in the near term.
"I don't think oncologists should be put in the position of rationing based on cost, but they do need to consider out-of-pocket costs when prescribing," Dr Ramsey told Medscape Medical News. "Not completing expensive treatments due to financial burden may be worse than completing a therapy that is affordable."
"It's not a world that I want for cancer care, but I don't see other viable options in the near term," he explained. "To get changes in Medicare to allow negotiation, we need a functional Congress. Not likely soon."
Making Tradeoffs
Many experts have weighed in on the cost of drugs, both in cancer and other diseases. Dr Ramsey and his colleagues agree that the current model for cancer drug pricing is not sustainable and can be harmful to patients.
But solutions that attempt to balance access, affordability, and incentives to innovate might have a downside, they note.
They could, in fact, create "situations where low-value drugs are not available except outside of the insurance system."
Value in cancer care has become a hot topic because high price tags do not necessarily translate into high-quality care or improved outcomes. Thus, various strategies, such as those proposed by the American Society of Clinical Oncology, have sought to define the actual "value" of a cancer treatment.
But Dr Ramsey's team proposes taking it a step further. They think that insurers should not be forced to cover low-value drugs.
Several states currently mandate coverage of all cancer drugs for all approved indications. And with only a few exceptions, Medicare is explicitly prohibited from negotiating prices or excluding any drugs from its formulary.
Without the ability to refuse coverage, the authors argue, health insurers become severely compromised during price negotiations. To address high costs, drugs are put into copay tiers, which can become very expensive for the patient.
"We believe eliminating or narrowing mandatory coverage laws for cancer drugs represents the preferable and most equitable option," they write.
Patient acceptance of this type of policy would largely depend on having "compelling evidence" to support this move.
Holly Campbell, a spokesperson for the Pharmaceutical Research and Manufacturers of America, pointed out that a great deal of leverage is already available, without the need to impose restrictions.
"Significant negotiation already occurs between manufacturers and payers in the commercial space and in Medicare Part D," she told Medscape Medical News. "This is one reason why we've been able to bring more than 500 new medicines to patients since 2000, and spending on medicines has been a consistent share of overall healthcare spending."
In addition to aggressively negotiating drug prices, payers have extensive tools to drive patients to preferred lower-cost drugs on a formulary or to not place a medicine on a formulary, Campbell noted. "These include strategies such as prior authorization or step therapy, which prevent patients from accessing certain medicines without first satisfying plan-established protocols."
"While discussions about cost are important, we need to make sure they are centered on high-quality patient-centered care and encourage the development of innovative, life-changing medicines," she added.
Paradigm Shift Needed
The industry has argued that any attempt to reduce prices would stifle innovation, Dr Ramsey and colleagues explain. But that fear might be unfounded, they add.
They note that a number of factors, such as patent protections, advances in technology, and the accelerated approval program of the US Food and Drug Administration, might be lowering the cost of cancer drug discovery and development.
"These factors, along with the high value society places on better cancer drugs, are huge incentives for innovation," they write.
The consequence of their recommendations would most likely be that a low-benefit product would not survive the development process.
"For example, a product found to improve patient survival by a few weeks with a significant adverse-effect profile might be shelved rather than taken through the full approval process," the authors explain.
Another option could be variable pricing, based on the benefits by indication, they add.
"Without a doubt, we are sorely in need of policy reform," said Yousuf Zafar MD, associate professor of medicine and public policy at the Duke Cancer Institute in Durham, North Carolina.
We need more than reform; we need a paradigm shift.
"While each of these reforms individually might not have much of an impact, together they could potentially reduce costs for patients," he told Medscape Medical News.
"Personally, I wholeheartedly agree with the need for such reforms," Dr Zafar added. "However, in our current political environment, they are not necessarily politically palatable. In short, we need more than reform; we need a paradigm shift."
It's hard to think of other situations in which we would quibble about these points.
However, concerns about the proposed interventions were expressed by Leonard Saltz, MD, chief of gastrointestinal oncology at the Memorial Sloan Kettering Cancer Center in New York City.
Consider what Dr Ramsey's team is advocating, he said. "The right for the buyer to negotiate a price with the seller, the right for the buyer to choose not to buy if the seller does not bring the price into line with the value that the buyer perceives the product to offer, and the need for transparency throughout this process so that both buyer, seller, and everyone else can see just what is being offered and what is being asked."
"It's hard to think of other situations in which we would quibble about these points," Dr Saltz emphasized.
The editorialists have disclosed no relevant financial relationships.
JAMA Oncol. Published online February 11, 2016. Editorial
miércoles, 22 de noviembre de 2017
Cancer Cost: Drugs Not the Primary Culprit
News > Oncology Medscape Oncology
Drivers of Cancer Cost: Drugs Not the Primary Culprit
Roxanne Nelson, BSN, RN
April 08, 2016
With all the publicity in recent years about the prices of cancer drugs, it has become a common belief that the cost of cancer care has risen disproportionately in comparison to other healthcare costs. But that might not be the case.
A new study, commissioned by the Community Oncology Alliance (COA) and conducted by the actuarial firm Milliman, shows that cost increases for a 10-year period (2004 to 2014) were essentially the same for cancer patients receiving active treatment as for the noncancer population.
This was true for patients covered by Medicare fee-for-service (FFS) and those covered by commercial insurance.
Another key finding was that the per-patient cost of drugs is increasing at a much higher rate than other components of care. These increases have been largely fueled by biologics that have entered the market, but increases in drug costs have been offset by slower growth in other components.
The third key finding of the study is that since 2004, the site of service for outpatient chemotherapy infusion has dramatically shifted from the lower-cost physician's office to higher-cost hospital outpatient settings.
"If you actually look at oncology costs and per-patient spending, we thought that it would have gone up during that time period," said COA board member David Eagle, MD, a practicing oncologist at Lake Norman Oncology in Mooresville, North Carolina, who was a member of the study team.
The costs of cancer care are escalating, but that can be attributed to a number of factors, such as demographics and survivorship, Dr Eagle told Medscape Medical News. But the study shows that the costs of cancer care are not rising more than the cost of care for other conditions, which, he said, is "somewhat of a surprising finding."
This is somewhat of a surprising finding.
There have been many recent studies and analyses looking at the factors contributing to the cost of cancer care, but this study looked at they way oncology dollars are being spent, Dr Eagle explained.
"This will help put it in better perspective," he said. "For example, drugs get all of the attention when it comes to cost, but they are really just 20%."
"When we put it into a pie chart, it's just one slice," Dr Eagle noted. "While drug costs are important, the whole pie chart needs to be scrutinized."
Drugs, of course, need to be part of the discussion on costs, "but they shouldn't be the only part of the discussion," he pointed out.
Increases in Drug Spending
The goal of the analysis was to identify trends in the overall and component costs of cancer care from 2004 to 2014 and to create comparisons in cost trends with the general population.
The researchers analyzed the annual prevalence and per-patient costs of those undergoing cancer therapy using the Medicare 5% sample claim database and the Truven MarketScan commercial claim database.
The analysis did not include drugs provided under Medicare Part D.
For Medicare beneficiaries, there was an annual per-patient increase of 35.2% for the total population, 36.4% for actively treated cancer patients, and 34.8% for the noncancer population
Findings were similar for those with commercial insurance. There was an annual per-patient increase of 62.9% for the total population, 62.5% for cancer patients, and 60.8% for the noncancer population.
As expected, the researchers did find large increases in spending for cancer drugs. The portion of these costs associated with all types of chemotherapy increased during the study period from 15% to 18% in the Medicare population and from 15% to 20% in the commercially insured population.
In particular, the portion of spending for biologic chemotherapies increased from 3% to 9% in the Medicare population and from 2% to 7% in patients with commercial insurance.
But while the portion of spending for cancer-directed pharmaceuticals increased during the study period, the portion of spending for inpatient care declined.
Site-of-Service Shift for Chemo
One of the most notable changes and cost drivers was the shift in the site of administration of chemotherapy — from the physician's office to the outpatient hospital setting.
From 2004 to 2014, the portion of chemotherapy infusions administered in hospital outpatient settings, which are generally more expensive than a physician's office, increased by at least 30%.
With this increase, there was a corresponding reduction in the use of the less-expensive physician's office.
Medicare spending would be about $2 billion lower if the site-of-service shift hadn't happened.
If the site of chemotherapy infusion in 2014 had been maintained at 2004 levels, the estimated Medicare FFS cost per patient would have been approximately 7.5% lower for Medicare in 2014 — at 51,900 per Medicare FFS patient instead of the observed $56,100.
For commercially insured patients, it would have been $89,900 instead of the $95,400 observed (5.8% lower).
"We estimate that Medicare spending would be about $2 billion lower if the site-of-service shift hadn't happened," said Dr Eagle.
Points to Ponder
This retrospective analysis confirms what health service researchers have been saying, said Jonas de Souza, MD, assistant professor of medicine in hematology/oncology at the University of Chicago Medical Center.
"The costs of cancer drugs are increasing exponentially, and site-of-care costs are also increasing," he told Medscape Medical News. "It would be really interesting to understand the impact on the patient — in terms of survival, out-of-pocket costs, and financial toxicity — of these increases over the same time trend."
Although the finding that costs have been essentially the same in actively treated cancer patients and the noncancer population is interesting, "this fact should not by any means be simply translated into, 'healthcare costs are increasing all over the board'," Dr de Souza explained.
The study reports relative increases, not absolute values, he pointed out. The 20% increase ($8000) in costs for cancer patients — from $40,000 to $48,000 — has a much larger impact on the system than the 20% increase ($2000) in costs for noncancer patients — from $10,000 to $12,000.
"Cancer patients are more expensive and we have short-, intermediate-, and long-term problems if this pace of cost increases is maintained," he said.
Another issue is drug spending. "Even though it is not the only cost driver, it has increased at the highest rate of all component costs, fueled by new biologic cancer drugs," Dr de Souza reported.
This could become very expensive. "We are treating more cancer patients, and for longer periods of time, and with more expensive drugs," he said, noting that in some cases, cancer has become a chronic disease.
Dr de Souza said he agrees with the third key point highlighted in the study — that site of care is important. "The authors modeled what would have happened if the site of care had not shifted to the hospital outpatient setting," he explained. "However, equally important would have been to model what would have happened had the increase in drug costs followed the pattern prior to 2004."
This report was commissioned by Community Oncology Alliance, which received financial support from Bayer, Bristol-Myers Squibb, Eli Lilly and Company, Janssen Pharmaceuticals, Merck, Pfizer, the Pharmaceutical Research and Manufacturers of America (PhRMA), and Takeda.
Metastatic Prostate Cancer: Immuno-Cold or the Tip of the Iceberg?
Perspective > Current Opinion in Urology
Immunotherapy for Metastatic Prostate Cancer
Immuno-Cold or the Tip of the Iceberg?
Andrew L. Laccetti; Sumit K. Subudhi
Disclosures
Curr Opin Urol. 2017;27(6):566-571.
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Abstract and Introduction
Abstract
Purpose of review: Metastatic castration-resistant prostate cancer is in critical need of new and innovative treatment strategies. Since the approval of sipuleucel-T, the investigatory climate of prostate cancer immunotherapy has been rapidly evolving with promising developments in vaccine and immune checkpoint therapies.
Recent findings: Sipuleucel-T remains the first and only therapeutic cancer vaccine approved for its survival benefit in metastatic castration-resistant prostate cancer. Additional cancer vaccines are currently being evaluated, with the most promising being a peptide vaccine encoding prostate-specific antigen, known as prostate-specific antigen-TRICOM. Emerging data supports combinatorial strategies for vaccine therapy and a potential role for implementation in earlier stages of advanced disease. Immune checkpoint therapies have demonstrated limited success in prostate cancer with negative late phase trials for ipilimumab monotherapy and discouraging early phase results for programmed cell death protein 1 blockade. Novel immune-modulatory targets and rational combination strategies aim to produce more favorable results. Recent progress has been made to determine biologic predictors for response and toxicity in prostate cancer immunotherapy aiming to improve patient selection and safety.
Summary: Steady progress is anticipated in the field of prostate cancer immunotherapy including ongoing development of novel cancer vaccines, immune checkpoint therapies, and combinatorial strategies.
Immunotherapy for Metastatic Prostate Cancer
Immuno-Cold or the Tip of the Iceberg?
Andrew L. Laccetti; Sumit K. Subudhi
Disclosures
Curr Opin Urol. 2017;27(6):566-571.
Add to Email Alerts
Abstract and Introduction
Abstract
Purpose of review: Metastatic castration-resistant prostate cancer is in critical need of new and innovative treatment strategies. Since the approval of sipuleucel-T, the investigatory climate of prostate cancer immunotherapy has been rapidly evolving with promising developments in vaccine and immune checkpoint therapies.
Recent findings: Sipuleucel-T remains the first and only therapeutic cancer vaccine approved for its survival benefit in metastatic castration-resistant prostate cancer. Additional cancer vaccines are currently being evaluated, with the most promising being a peptide vaccine encoding prostate-specific antigen, known as prostate-specific antigen-TRICOM. Emerging data supports combinatorial strategies for vaccine therapy and a potential role for implementation in earlier stages of advanced disease. Immune checkpoint therapies have demonstrated limited success in prostate cancer with negative late phase trials for ipilimumab monotherapy and discouraging early phase results for programmed cell death protein 1 blockade. Novel immune-modulatory targets and rational combination strategies aim to produce more favorable results. Recent progress has been made to determine biologic predictors for response and toxicity in prostate cancer immunotherapy aiming to improve patient selection and safety.
Summary: Steady progress is anticipated in the field of prostate cancer immunotherapy including ongoing development of novel cancer vaccines, immune checkpoint therapies, and combinatorial strategies.
Gut Microbiome Is a Key Variable in Immunotherapy Efficacy
Perspective MEDscape Oncology
COMMENTARY
Strong Evidence Emerging That Gut Microbiome Is a Key Variable in Immunotherapy Efficacy
Theodore Bosworth
November 13, 2017
Immunologic fitness orchestrated by the gut microbiome is strongly suspected of mediating response to cancer treatments, according to an area of research that is heating up quickly. Experimental studies published by independent research groups over the past 5 years have made this hypothesis increasingly plausible. Not least intriguing, the specific mix of commensal intestinal microflora may explain why only a limited proportion of patients achieve long-term responses to checkpoint inhibitors.
"I want to convince you that the microbiome can actually dictate the cancer immune set-point," said Laurence Zitvogel, MD, PhD, group leader, Tumor Immunology and Immunotherapy, Institut Gustave Roussy, Villejuif, France. As one of the scientists who is active in this area of research, she was given the task of summarizing progress in a special symposium on immunotherapy biomarkers at the 2017 annual meeting of the European Society for Medical Oncology.
Several studies in experimental models have demonstrated an interaction between the intestinal microbiome and the antitumor activity of cytotoxic agents with immunostimulatory effects, according to Dr Zitvogel. In one early example, gut dysbiosis induced by vancomycin was shown to greatly inhibit the antitumor effect of cyclophosphamide.[1] This change in antitumor effect has been linked subsequently to several changes in type 1 helper (Th1) CD4+ cell activity, according to Dr Zitvogel, but the reduced trafficking of these cells into the tumor bed may be particularly relevant to immunotherapies.
"One of the dominating mechanisms appears to involve how the gut microbiome affects expression of CCR9," Dr Zitvogel explained. CCR9, a chemokine receptor, is most closely associated with lymphocyte homing to the gut, but the ligand for CCR9, CCL25, can also be expressed in tumors. There is evidence to suggest that CCR9 priming by gut microflora plays a role in sending lymphocytes to cancers and in initiating signaling that "transforms a cold tumor into a hot tumor," said Dr Zitvogel, referring to antitumor immunologic activity. In one set of experiments tracing the effect of CCR9 expression, the ratio of antitumor CD4+ T cells to suppressor T-regulatory cells was "tremendously increased" in tumors of mice with a healthy gut microbiome relative to those in which the gut microbiome had been compromised.
Understanding the impact of the gut microbiome on immune function may be the key to developing consistently effective immunotherapy.
According to Dr Zitvogel, understanding the impact of the gut microbiome on immune function may be the key to developing consistently effective immunotherapy. In about 20%-30% of patients, checkpoint inhibitors have produced what appears to be cure in an array of cancer types. A defect in immunologic function mediated by the gut microbiome may be the explanation for the limited or absent response in the remaining 70%-80%.
The basis for this hypothesis begins with the overwhelming evidence of symbiosis between gut microbiota and the immune system. Although the impact on the gut microbiome for regulating disease risk is the focus in almost every corner of clinical medicine, ranging from obesity to mood disorders, there appears to be a special relationship between the gut microbiome and immune surveillance and activation. The ability of the immune system to tolerate the vast number of commensal microflora in the gut without losing its ability to recognize and eliminate pathogens must require a complex interaction, according to Dr Zitvogel.
"Immunologists will tell you that most of the anticancer immunity takes place in the lymph nodes, but actually we now know that [the] intestinal barrier contains the vast majority of the immune system spread over a 200-m2 surface and is constantly interacting with bacteria, parasites, and other bugs. On this surface, a mutual symbiosis has developed [to permit the immune system] to recognize antigens," Dr Zitvogel said. She believes the evidence also supports a role for this symbiosis in maturation of the immune system as well as functions beyond immunologic activity, including basic metabolism.
As has been repeatedly noted in the increasing interest in the role of the gut microbiome, the human intestine contains tens of trillions of microbes. Most are bacteria, but there are a variety of other organisms representing thousands of different species. The intestinal metagenome of these organisms has been estimated to outnumber the size of the human genome by a factor of 150, according to Dr Zitvogel. In the series of studies suggesting a relationship among the microbiome, immune function, and the efficacy of cancer treatments, the challenge has been to unravel the signaling pathways. These are not expected to be simple.
Greater numbers of organisms favorable to a healthy microbiome have been associated with greater anticancer effect from immunotherapy.
"The algorithm is complex because there is a delicate triangle among the gut microbiome, the intestinal immune system, and systemic immune function," Dr Zitvogel said. When the natural balance in this triangle is disturbed, one of the potential consequences appears to be a reduction in effective immunosurveillance. In other words, the usual immune set-point that characterizes a well-functioning system to activate normal immune-driven anticancer activity is lost, according to Dr Zitvogel.
The adverse impact of vancomycin on the efficacy of cyclophosphamide has been reproduced with other immunostimulatory drugs, which now includes checkpoint inhibitors. Citing several studies, Dr Zitvogel noted that overall survival and progression-free survival has been found to be lower in patients exposed to antibiotics just before anti–PD-1 therapy relative to those who were not. In one study that tested this association in a multivariate regression analysis, recent exposure to antibiotics, which presumably alters the microbiome, remained a strong risk factor for a poor response.
Of many directions of research, one has been to isolate commensal bacterial species that predict an improved response to checkpoint inhibitors. In a series of studies conducted in animal models with the anti–CTLA-4 monoclonal antibody ipilimumab at Dr Zitvogel's center, the introduction of Bacteroides fragilis and Bacteroides thetaiotaomicron were associated with restoration of anti–CTLA-4 anticancer responses in mice who had been poorly responsive after previously induced dysbiosis.[2] It is notable that other centers performing related experiments have associated some of the same bacteria with an improved response to checkpoint inhibition.
"With thousands of different species in the gut, it is interesting that different teams are identifying the same bugs," Dr Zitvogel said. She also noted that several groups, including her own, have found a dose effect for this relationship so that greater numbers of organisms favorable to a healthy microbiome have been associated with greater anticancer effect from immunotherapy.
In an even more impressive demonstration, response to checkpoint inhibitors in a mouse model can be altered with gut bacteria from patients who did or did not respond to a checkpoint inhibitor, according to Dr Zitvogel. Describing this experiment, Dr Zitvogel explained that feces from checkpoint inhibitor responders or nonresponders were introduced into the gut of germ-free mice. After a delay to allow the gut microbiome to adjust, cancer treatment was initiated with a checkpoint inhibitor. According to Dr Zitvogel, the mice that received feces from patients who progressed on a checkpoint inhibitor achieve a smaller response than those that received feces from responders.
Blocking checkpoint proteins has been compared with removing the brake on a car. Like a car on a flat surface, removing the brake on immune response may not be enough. Rather, some push or acceleration is needed. This may be the role of a healthy balance of gut microflora, according to Dr Zitvogel. She suggested that a microbiome in balance with the immune system increases T-cell activity and sends T cells into tumors to attack cancer cells. She believes that the gut microbiome controls the immune set-point, which triggers the immune response.
"To have immune fitness, you need a healthy gut. This is the take-home message," Dr Zitvogel said. Although she conceded that there are many unanswered questions about how to define dysbiosis and how best to restore the gut microbiome to health once dysbiosis is found, she thinks this area of investigation is fundamental to the future of immuno-oncology.
COMMENTARY
Strong Evidence Emerging That Gut Microbiome Is a Key Variable in Immunotherapy Efficacy
Theodore Bosworth
November 13, 2017
Immunologic fitness orchestrated by the gut microbiome is strongly suspected of mediating response to cancer treatments, according to an area of research that is heating up quickly. Experimental studies published by independent research groups over the past 5 years have made this hypothesis increasingly plausible. Not least intriguing, the specific mix of commensal intestinal microflora may explain why only a limited proportion of patients achieve long-term responses to checkpoint inhibitors.
"I want to convince you that the microbiome can actually dictate the cancer immune set-point," said Laurence Zitvogel, MD, PhD, group leader, Tumor Immunology and Immunotherapy, Institut Gustave Roussy, Villejuif, France. As one of the scientists who is active in this area of research, she was given the task of summarizing progress in a special symposium on immunotherapy biomarkers at the 2017 annual meeting of the European Society for Medical Oncology.
Several studies in experimental models have demonstrated an interaction between the intestinal microbiome and the antitumor activity of cytotoxic agents with immunostimulatory effects, according to Dr Zitvogel. In one early example, gut dysbiosis induced by vancomycin was shown to greatly inhibit the antitumor effect of cyclophosphamide.[1] This change in antitumor effect has been linked subsequently to several changes in type 1 helper (Th1) CD4+ cell activity, according to Dr Zitvogel, but the reduced trafficking of these cells into the tumor bed may be particularly relevant to immunotherapies.
"One of the dominating mechanisms appears to involve how the gut microbiome affects expression of CCR9," Dr Zitvogel explained. CCR9, a chemokine receptor, is most closely associated with lymphocyte homing to the gut, but the ligand for CCR9, CCL25, can also be expressed in tumors. There is evidence to suggest that CCR9 priming by gut microflora plays a role in sending lymphocytes to cancers and in initiating signaling that "transforms a cold tumor into a hot tumor," said Dr Zitvogel, referring to antitumor immunologic activity. In one set of experiments tracing the effect of CCR9 expression, the ratio of antitumor CD4+ T cells to suppressor T-regulatory cells was "tremendously increased" in tumors of mice with a healthy gut microbiome relative to those in which the gut microbiome had been compromised.
Understanding the impact of the gut microbiome on immune function may be the key to developing consistently effective immunotherapy.
According to Dr Zitvogel, understanding the impact of the gut microbiome on immune function may be the key to developing consistently effective immunotherapy. In about 20%-30% of patients, checkpoint inhibitors have produced what appears to be cure in an array of cancer types. A defect in immunologic function mediated by the gut microbiome may be the explanation for the limited or absent response in the remaining 70%-80%.
The basis for this hypothesis begins with the overwhelming evidence of symbiosis between gut microbiota and the immune system. Although the impact on the gut microbiome for regulating disease risk is the focus in almost every corner of clinical medicine, ranging from obesity to mood disorders, there appears to be a special relationship between the gut microbiome and immune surveillance and activation. The ability of the immune system to tolerate the vast number of commensal microflora in the gut without losing its ability to recognize and eliminate pathogens must require a complex interaction, according to Dr Zitvogel.
"Immunologists will tell you that most of the anticancer immunity takes place in the lymph nodes, but actually we now know that [the] intestinal barrier contains the vast majority of the immune system spread over a 200-m2 surface and is constantly interacting with bacteria, parasites, and other bugs. On this surface, a mutual symbiosis has developed [to permit the immune system] to recognize antigens," Dr Zitvogel said. She believes the evidence also supports a role for this symbiosis in maturation of the immune system as well as functions beyond immunologic activity, including basic metabolism.
As has been repeatedly noted in the increasing interest in the role of the gut microbiome, the human intestine contains tens of trillions of microbes. Most are bacteria, but there are a variety of other organisms representing thousands of different species. The intestinal metagenome of these organisms has been estimated to outnumber the size of the human genome by a factor of 150, according to Dr Zitvogel. In the series of studies suggesting a relationship among the microbiome, immune function, and the efficacy of cancer treatments, the challenge has been to unravel the signaling pathways. These are not expected to be simple.
Greater numbers of organisms favorable to a healthy microbiome have been associated with greater anticancer effect from immunotherapy.
"The algorithm is complex because there is a delicate triangle among the gut microbiome, the intestinal immune system, and systemic immune function," Dr Zitvogel said. When the natural balance in this triangle is disturbed, one of the potential consequences appears to be a reduction in effective immunosurveillance. In other words, the usual immune set-point that characterizes a well-functioning system to activate normal immune-driven anticancer activity is lost, according to Dr Zitvogel.
The adverse impact of vancomycin on the efficacy of cyclophosphamide has been reproduced with other immunostimulatory drugs, which now includes checkpoint inhibitors. Citing several studies, Dr Zitvogel noted that overall survival and progression-free survival has been found to be lower in patients exposed to antibiotics just before anti–PD-1 therapy relative to those who were not. In one study that tested this association in a multivariate regression analysis, recent exposure to antibiotics, which presumably alters the microbiome, remained a strong risk factor for a poor response.
Of many directions of research, one has been to isolate commensal bacterial species that predict an improved response to checkpoint inhibitors. In a series of studies conducted in animal models with the anti–CTLA-4 monoclonal antibody ipilimumab at Dr Zitvogel's center, the introduction of Bacteroides fragilis and Bacteroides thetaiotaomicron were associated with restoration of anti–CTLA-4 anticancer responses in mice who had been poorly responsive after previously induced dysbiosis.[2] It is notable that other centers performing related experiments have associated some of the same bacteria with an improved response to checkpoint inhibition.
"With thousands of different species in the gut, it is interesting that different teams are identifying the same bugs," Dr Zitvogel said. She also noted that several groups, including her own, have found a dose effect for this relationship so that greater numbers of organisms favorable to a healthy microbiome have been associated with greater anticancer effect from immunotherapy.
In an even more impressive demonstration, response to checkpoint inhibitors in a mouse model can be altered with gut bacteria from patients who did or did not respond to a checkpoint inhibitor, according to Dr Zitvogel. Describing this experiment, Dr Zitvogel explained that feces from checkpoint inhibitor responders or nonresponders were introduced into the gut of germ-free mice. After a delay to allow the gut microbiome to adjust, cancer treatment was initiated with a checkpoint inhibitor. According to Dr Zitvogel, the mice that received feces from patients who progressed on a checkpoint inhibitor achieve a smaller response than those that received feces from responders.
Blocking checkpoint proteins has been compared with removing the brake on a car. Like a car on a flat surface, removing the brake on immune response may not be enough. Rather, some push or acceleration is needed. This may be the role of a healthy balance of gut microflora, according to Dr Zitvogel. She suggested that a microbiome in balance with the immune system increases T-cell activity and sends T cells into tumors to attack cancer cells. She believes that the gut microbiome controls the immune set-point, which triggers the immune response.
"To have immune fitness, you need a healthy gut. This is the take-home message," Dr Zitvogel said. Although she conceded that there are many unanswered questions about how to define dysbiosis and how best to restore the gut microbiome to health once dysbiosis is found, she thinks this area of investigation is fundamental to the future of immuno-oncology.
miércoles, 8 de noviembre de 2017
Immunotherapy Continues to Impress in GU Malignancies
Web Exclusives >
Immunotherapy Continues to Impress in GU Malignancies
Angelica Welch
Published Online: Tuesday, Nov 07, 2017
Andrea Apolo, MD
Single-agent immunotherapy continues to demonstrate durable responses in patients with urothelial carcinoma, and now, combination regimens are showing efficacy in both urothelial carcinoma and rarer genitourinary (GU) tumors.
In a phase I study, the combinations of cabozantinib (Cabometyx) plus nivolumab (Opdivo), as well as cabozantinib plus nivolumab and ipilimumab (Yervoy), are being investigated in patients with GU malignancies.1 Findings showed that, in the overall study population, the overall response rate (ORR) was 33%. Moreover, the ORRs with cabozantinib and nivolumab, and cabozantinib, nivolumab, and ipilimumab, were 38% and 22%, respectively.
In addition to patients with metastatic urothelial carcinoma, rare GU tumors such as penile cancer, testicular cancer, and adenocarcinoma of the bladder are responding to these therapies, as well.
Additionally, the anti–PD-L1 agent avelumab (Bavencio) showed durable responses in the phase Ib JAVELIN Solid Tumor study, an updated analysis of which was presented at the 2017 ESMO Congress.2
Andrea Apolo, MD, presented the results, which showed that the ORR in the 249 patients evaluated in the study was 17.3% (95% CI, 12.8%-22.5%), with a complete response rate of 4.4%. The disease control rate was 44.6% and the median overall survival was 8.2 months (95% CI, 6.3-10.8).
In an interview with OncLive at ESMO, Apolo, chief of the Bladder Cancer Section of the Genitourinary Malignancies Branch at the National Cancer Institute, discussed the combination of cabozantinib plus nivolumab and ipilimumab, as well as the updated analysis of avelumab in urothelial carcinoma.
OncLive: Can you summarize the early findings with cabozantinib and nivolumab, with and without ipilimumab?
Apolo: At the 2017 ESMO Congress, we presented the final results of the phase I cohort of the combination of cabozantinib with nivolumab, and cabozantinib with nivolumab and ipilimumab. The trial is still open, and we have multiple cohorts still enrolling in the expansion cohort, but the phase I findings that we are presenting here have the longest follow-up.
We found very nice activity throughout multiple GU tumors, so this is not only bladder cancer or kidney cancer; it’s all GU tumors, including renal cancer, prostate cancer, and, importantly, rare GU tumors such as squamous cell carcinoma of the bladder, adenocarcinoma of the bladder, testicular cancer, and penile cancer. We saw responses in these rare tumors with the combination.
One of the things that we focused on during this presentation was safety. We wanted to see if the combination was tolerable and whether there were additive toxicities. We did see additive toxicities that were grade 1/2—predominantly nausea, vomiting, fatigue, and laboratory abnormalities, such as hyperthyroidism. We also saw some grade 1/2 elevation of liver function tests, which was something that we were really worried about. However, they were all very manageable, so that was exciting because if we want to bring this combination forward into larger trials, we need to make sure it is safe.
There were some big results presented at the 2017 ESMO Congress. How do you look at these results in conjunction with your findings?
It shows that cabozantinib is active and nivolumab is active…and combining them just makes sense because we want to increase the activity that we are seeing in these patients.
Can you discuss your findings with avelumab?
We have the updated data from avelumab as monotherapy in patients with metastatic urothelial carcinoma who are refractory to platinum-based chemotherapy. We had 249 patients in the cohort, and [have data at] 20 months’ follow-up. We are seeing durable responses, which is very important. At 1 year, 70% of [responding] patients are still responding. In terms of toxicity, we did not see any more toxicity with the longer follow-up—about 11% grade 3/4 toxicities. This is very consistent with our earlier reports.
With 5 checkpoint inhibitors in the bladder cancer space, how could these results help clinicians pick the right therapy?
That’s a good question. I don't know if there is a good algorithm to pick among the 5 checkpoint inhibitors that are approved for metastatic urothelial carcinoma. They are all active; the trial is very little in terms of ORR, overall survival, and progression-free survival, so it is based on availability. But I always say, if possible, enroll in a clinical trial.
That is the most important thing because, as we try to build on the activity, we are moving toward combination therapies. There are a lot of clinical trials open now; if you can enroll your patient into a clinical trial, we can then learn about the cumulative responses that could potentially occur synergistically with different mechanisms of action. We have seen increased immune/immune combinations, immune/chemotherapy combinations, and then, with our trial, immunotherapy with TKIs.
There has been a lot mentioned about tumor burden and biomarkers in this space. Could you share your insight on that?
In terms of selecting patients with bladder cancer based on biomarkers, there are a lot of studies going on; there are a lot of things that we are looking at. Mutational burden is one of them, and it does seem to be correlated with overall outcomes. Can we select patients based on this? Not yet. Just like PD-L1, there is also a correlation; we are still trying to figure out the value. Combining biomarkers together may be the key way to select these patients and there are correlations, but we cannot yet use them to select patients for treatment.
Immunotherapy Continues to Impress in GU Malignancies
Angelica Welch
Published Online: Tuesday, Nov 07, 2017
Andrea Apolo, MD
Single-agent immunotherapy continues to demonstrate durable responses in patients with urothelial carcinoma, and now, combination regimens are showing efficacy in both urothelial carcinoma and rarer genitourinary (GU) tumors.
In a phase I study, the combinations of cabozantinib (Cabometyx) plus nivolumab (Opdivo), as well as cabozantinib plus nivolumab and ipilimumab (Yervoy), are being investigated in patients with GU malignancies.1 Findings showed that, in the overall study population, the overall response rate (ORR) was 33%. Moreover, the ORRs with cabozantinib and nivolumab, and cabozantinib, nivolumab, and ipilimumab, were 38% and 22%, respectively.
In addition to patients with metastatic urothelial carcinoma, rare GU tumors such as penile cancer, testicular cancer, and adenocarcinoma of the bladder are responding to these therapies, as well.
Additionally, the anti–PD-L1 agent avelumab (Bavencio) showed durable responses in the phase Ib JAVELIN Solid Tumor study, an updated analysis of which was presented at the 2017 ESMO Congress.2
Andrea Apolo, MD, presented the results, which showed that the ORR in the 249 patients evaluated in the study was 17.3% (95% CI, 12.8%-22.5%), with a complete response rate of 4.4%. The disease control rate was 44.6% and the median overall survival was 8.2 months (95% CI, 6.3-10.8).
In an interview with OncLive at ESMO, Apolo, chief of the Bladder Cancer Section of the Genitourinary Malignancies Branch at the National Cancer Institute, discussed the combination of cabozantinib plus nivolumab and ipilimumab, as well as the updated analysis of avelumab in urothelial carcinoma.
OncLive: Can you summarize the early findings with cabozantinib and nivolumab, with and without ipilimumab?
Apolo: At the 2017 ESMO Congress, we presented the final results of the phase I cohort of the combination of cabozantinib with nivolumab, and cabozantinib with nivolumab and ipilimumab. The trial is still open, and we have multiple cohorts still enrolling in the expansion cohort, but the phase I findings that we are presenting here have the longest follow-up.
We found very nice activity throughout multiple GU tumors, so this is not only bladder cancer or kidney cancer; it’s all GU tumors, including renal cancer, prostate cancer, and, importantly, rare GU tumors such as squamous cell carcinoma of the bladder, adenocarcinoma of the bladder, testicular cancer, and penile cancer. We saw responses in these rare tumors with the combination.
One of the things that we focused on during this presentation was safety. We wanted to see if the combination was tolerable and whether there were additive toxicities. We did see additive toxicities that were grade 1/2—predominantly nausea, vomiting, fatigue, and laboratory abnormalities, such as hyperthyroidism. We also saw some grade 1/2 elevation of liver function tests, which was something that we were really worried about. However, they were all very manageable, so that was exciting because if we want to bring this combination forward into larger trials, we need to make sure it is safe.
There were some big results presented at the 2017 ESMO Congress. How do you look at these results in conjunction with your findings?
It shows that cabozantinib is active and nivolumab is active…and combining them just makes sense because we want to increase the activity that we are seeing in these patients.
Can you discuss your findings with avelumab?
We have the updated data from avelumab as monotherapy in patients with metastatic urothelial carcinoma who are refractory to platinum-based chemotherapy. We had 249 patients in the cohort, and [have data at] 20 months’ follow-up. We are seeing durable responses, which is very important. At 1 year, 70% of [responding] patients are still responding. In terms of toxicity, we did not see any more toxicity with the longer follow-up—about 11% grade 3/4 toxicities. This is very consistent with our earlier reports.
With 5 checkpoint inhibitors in the bladder cancer space, how could these results help clinicians pick the right therapy?
That’s a good question. I don't know if there is a good algorithm to pick among the 5 checkpoint inhibitors that are approved for metastatic urothelial carcinoma. They are all active; the trial is very little in terms of ORR, overall survival, and progression-free survival, so it is based on availability. But I always say, if possible, enroll in a clinical trial.
That is the most important thing because, as we try to build on the activity, we are moving toward combination therapies. There are a lot of clinical trials open now; if you can enroll your patient into a clinical trial, we can then learn about the cumulative responses that could potentially occur synergistically with different mechanisms of action. We have seen increased immune/immune combinations, immune/chemotherapy combinations, and then, with our trial, immunotherapy with TKIs.
There has been a lot mentioned about tumor burden and biomarkers in this space. Could you share your insight on that?
In terms of selecting patients with bladder cancer based on biomarkers, there are a lot of studies going on; there are a lot of things that we are looking at. Mutational burden is one of them, and it does seem to be correlated with overall outcomes. Can we select patients based on this? Not yet. Just like PD-L1, there is also a correlation; we are still trying to figure out the value. Combining biomarkers together may be the key way to select these patients and there are correlations, but we cannot yet use them to select patients for treatment.
domingo, 5 de noviembre de 2017
Marijuana Cancer Cure Claims: FDA Cracks Down
News > Oncology
FDA Cracks Down on Marijuana Cancer Cure Claims
Nick Mulcahy
November 01, 2017
The US Food and Drug Administration (FDA) has issued warning letters to four companies selling products online that allegedly contain cannabidiol, which is a nonintoxicating component of the marijuana plant. The companies claim that their products can prevent, treat, or cure cancer.
The cancer claims are not supported by evidence, the FDA points out.
Selling unapproved products with unsubstantiated therapeutic claims is a violation of the Federal Food, Drug and Cosmetic Act and thus is illegal.
The four companies are Greenroads Health, Natural Alchemist, That’s Natural! Marketing and Consulting, and Stanley Brothers Social Enterprises LLC. Each company markets cannabidiol online in a variety of product types, such as oil drops, capsules, syrups, teas, topical lotions, and creams.
The warning letters are part of an ongoing campaign from the FDA to curb healthcare fraud. In April, the agency issued more than a dozen other warning letters to companies marketing "bogus cancer cures," as reported by Medscape Medical News.
Cannabidiol, or CBD, is a component of the marijuana or cannabis plant and is not FDA approved in any drug product for any indication. It is distinct from tetrahydrocannabinol, or THC, in marijuana, which is intoxicating.
However, cannabidiol is undergoing "substantial clinical investigation" as a cancer treatment, says the FDA.
For example, GW Pharmaceuticals and Otsuka Pharmaceutical Company currently are conducting a phase 2/3 trial in the United States to evaluate the efficacy and safety of Sativex, a cannabinoid formulation, in the treatment of pain in patients with advanced cancer who experience inadequate analgesia during optimized long-term opioid therapy.
FDA Commissioner Scott Gottlieb, MD, said the agency is in support of investigating marijuana-based products.
"We support sound, scientifically based research using components derived from marijuana, and we'll continue to work with product developers who are interested in bringing safe, effective, and quality products to market," he said in a press statement.
In the same statement, the FDA published examples of cannabidiol product claims culled from the four companies' websites:
"CBD combats tumor and cancer cells;";
"CBD makes cancer cells commit 'suicide' without killing other cells;
"CBD...[has] antiproliferative properties that inhibit cell division and growth in certain types of cancer, not allowing the tumor to grow;" and
"Nonpsychoactive cannabinoids like CBD may be effective in treating tumors from cancer ― including breast cancer."
It is possible that some of these claims may be accurate. Cannabidiol has been the subject of basic science studies as an anticancer agent. However, the claims that the companies are making have no place in product marketing, the FDA stressed.
Furthermore, the FDA is concerned not only about baseless and illegal product claims but also about driving cancer patients away from legitimate treatments.
"When people are allowed to illegally market agents that deliver no established benefit, they may steer patients away from products that have proven, antitumor effects that could extend lives," said Dr Gottlieb, who is a cancer survivor, having been successfully treated for Hodgkin's lymphoma.
However, there are only small numbers of such patients, a recent study suggests.
Researchers at Yale Cancer Center in New Haven, Connecticut, combed through 10 years (2004-2013) of records in the National Cancer Database to find 280 early-stage cancer patients (with either breast, prostate, lung, or colorectal disease) whose initial treatment was coded as "other-unproven: cancer treatment administered by nonmedical personnel."
Very few patients completely reject first-line conventional cancer treatment for alternative and unproven therapies.
Follow Medscape senior journalist Nick Mulcahy on Twitter: @MulcahyNick
For more from Medscape Oncology, follow us on Twitter: @MedscapeOnc
FDA Cracks Down on Marijuana Cancer Cure Claims
Nick Mulcahy
November 01, 2017
The US Food and Drug Administration (FDA) has issued warning letters to four companies selling products online that allegedly contain cannabidiol, which is a nonintoxicating component of the marijuana plant. The companies claim that their products can prevent, treat, or cure cancer.
The cancer claims are not supported by evidence, the FDA points out.
Selling unapproved products with unsubstantiated therapeutic claims is a violation of the Federal Food, Drug and Cosmetic Act and thus is illegal.
The four companies are Greenroads Health, Natural Alchemist, That’s Natural! Marketing and Consulting, and Stanley Brothers Social Enterprises LLC. Each company markets cannabidiol online in a variety of product types, such as oil drops, capsules, syrups, teas, topical lotions, and creams.
The warning letters are part of an ongoing campaign from the FDA to curb healthcare fraud. In April, the agency issued more than a dozen other warning letters to companies marketing "bogus cancer cures," as reported by Medscape Medical News.
Cannabidiol, or CBD, is a component of the marijuana or cannabis plant and is not FDA approved in any drug product for any indication. It is distinct from tetrahydrocannabinol, or THC, in marijuana, which is intoxicating.
However, cannabidiol is undergoing "substantial clinical investigation" as a cancer treatment, says the FDA.
For example, GW Pharmaceuticals and Otsuka Pharmaceutical Company currently are conducting a phase 2/3 trial in the United States to evaluate the efficacy and safety of Sativex, a cannabinoid formulation, in the treatment of pain in patients with advanced cancer who experience inadequate analgesia during optimized long-term opioid therapy.
FDA Commissioner Scott Gottlieb, MD, said the agency is in support of investigating marijuana-based products.
"We support sound, scientifically based research using components derived from marijuana, and we'll continue to work with product developers who are interested in bringing safe, effective, and quality products to market," he said in a press statement.
In the same statement, the FDA published examples of cannabidiol product claims culled from the four companies' websites:
"CBD combats tumor and cancer cells;";
"CBD makes cancer cells commit 'suicide' without killing other cells;
"CBD...[has] antiproliferative properties that inhibit cell division and growth in certain types of cancer, not allowing the tumor to grow;" and
"Nonpsychoactive cannabinoids like CBD may be effective in treating tumors from cancer ― including breast cancer."
It is possible that some of these claims may be accurate. Cannabidiol has been the subject of basic science studies as an anticancer agent. However, the claims that the companies are making have no place in product marketing, the FDA stressed.
Furthermore, the FDA is concerned not only about baseless and illegal product claims but also about driving cancer patients away from legitimate treatments.
"When people are allowed to illegally market agents that deliver no established benefit, they may steer patients away from products that have proven, antitumor effects that could extend lives," said Dr Gottlieb, who is a cancer survivor, having been successfully treated for Hodgkin's lymphoma.
However, there are only small numbers of such patients, a recent study suggests.
Researchers at Yale Cancer Center in New Haven, Connecticut, combed through 10 years (2004-2013) of records in the National Cancer Database to find 280 early-stage cancer patients (with either breast, prostate, lung, or colorectal disease) whose initial treatment was coded as "other-unproven: cancer treatment administered by nonmedical personnel."
Very few patients completely reject first-line conventional cancer treatment for alternative and unproven therapies.
Follow Medscape senior journalist Nick Mulcahy on Twitter: @MulcahyNick
For more from Medscape Oncology, follow us on Twitter: @MedscapeOnc
Prostate Cancer: Stereotactic body radiation therapy with CyberKnife Robotic Radiosurgery System
Centre for Reviews and Dissemination NIHR
Stereotactic body radiation therapy with CyberKnife Robotic Radiosurgery System (Accuray Inc.) boost treatment in primary localized prostate cancer
HAYES, Inc
Record Status
This is a bibliographic record of a published health technology assessment. No evaluation of the quality of this assessment has been made for the HTA database.
Citation
HAYES, Inc. Stereotactic body radiation therapy with CyberKnife Robotic Radiosurgery System (Accuray Inc.) boost treatment in primary localized prostate cancer
. Lansdale: HAYES, Inc. Healthcare Technology Brief Publication. 2016
Authors' objectives
Prostate cancer is expected to be the most common cancer diagnosed among men in the United States in 2016, comprising nearly 180,890 new cases with a projected 26,120 deaths.
In contrast to patients with lower-risk disease, those with locally confined high-risk prostate cancer and those with intermediate-risk disease with 2 or more risk factors typically have poorer prognoses requiring more intensified treatment.
High-dose-rate (HDR) brachytherapy is commonly used as a "boost" to conventionally fractionated external beam radiation therapy (EBRT) in this setting, but is highly invasive and resource-intensive. Extreme hypofractionated stereotactic body radiation therapy (SBRT) is emerging as a noninvasive alternative to HDR brachytherapy as a boost.
Description of Technology:
This health technology assessment focuses on the use of the CyberKnife SBRT platform to deliver boost therapy in men who have intermediate- to high-risk, localized prostate cancer.
Boost treatment with CyberKnife is intended to recapitulate radiation delivery doses and distribution profiles similar to those possible with HDR brachytherapy when used to boost standard EBRT dosage.
It does not require anesthetic, placement of intraprostatic catheters, or inpatient hospitalization. Gold fiducials are placed within the prostate to help identify and track the location of the gland and tumor. A treatment plan is developed based on a high-resolution computed tomography imaging study fused with a magnetic resonance image study to outline the prostate gland and fiducials. The CyberKnife computer-controlled robot slowly moves around the patient to deliver radiation from 150 to 300 angles. Five or fewer treatments, each lasting 30 to 90 minutes, are required.
Patient Population:
CyberKnife has been used in patients with previously untreated, localized prostate cancer, and in previously treated patients with advanced or recurrent prostate cancer. The patient population under consideration in this health technology assessment include treatment-naïve men with intermediate- to high-risk localized prostate cancer who receive definitive therapy with EBRT plus CyberKnife SBRT boost.
Clinical Alternatives:
Prostate cancer treatment is guided by the initial disease risk category. Options can include active surveillance or watchful waiting; radical prostatectomy; EBRT using 3-dimensional conformal radiation therapy or intensitymodulated radiotherapy; HDR brachytherapy; high-intensity-focused ultrasound; hormonal therapy; cryosurgery; or combinations thereof.
Stereotactic body radiation therapy with CyberKnife Robotic Radiosurgery System (Accuray Inc.) boost treatment in primary localized prostate cancer
HAYES, Inc
Record Status
This is a bibliographic record of a published health technology assessment. No evaluation of the quality of this assessment has been made for the HTA database.
Citation
HAYES, Inc. Stereotactic body radiation therapy with CyberKnife Robotic Radiosurgery System (Accuray Inc.) boost treatment in primary localized prostate cancer
. Lansdale: HAYES, Inc. Healthcare Technology Brief Publication. 2016
Authors' objectives
Prostate cancer is expected to be the most common cancer diagnosed among men in the United States in 2016, comprising nearly 180,890 new cases with a projected 26,120 deaths.
In contrast to patients with lower-risk disease, those with locally confined high-risk prostate cancer and those with intermediate-risk disease with 2 or more risk factors typically have poorer prognoses requiring more intensified treatment.
High-dose-rate (HDR) brachytherapy is commonly used as a "boost" to conventionally fractionated external beam radiation therapy (EBRT) in this setting, but is highly invasive and resource-intensive. Extreme hypofractionated stereotactic body radiation therapy (SBRT) is emerging as a noninvasive alternative to HDR brachytherapy as a boost.
Description of Technology:
This health technology assessment focuses on the use of the CyberKnife SBRT platform to deliver boost therapy in men who have intermediate- to high-risk, localized prostate cancer.
Boost treatment with CyberKnife is intended to recapitulate radiation delivery doses and distribution profiles similar to those possible with HDR brachytherapy when used to boost standard EBRT dosage.
It does not require anesthetic, placement of intraprostatic catheters, or inpatient hospitalization. Gold fiducials are placed within the prostate to help identify and track the location of the gland and tumor. A treatment plan is developed based on a high-resolution computed tomography imaging study fused with a magnetic resonance image study to outline the prostate gland and fiducials. The CyberKnife computer-controlled robot slowly moves around the patient to deliver radiation from 150 to 300 angles. Five or fewer treatments, each lasting 30 to 90 minutes, are required.
Patient Population:
CyberKnife has been used in patients with previously untreated, localized prostate cancer, and in previously treated patients with advanced or recurrent prostate cancer. The patient population under consideration in this health technology assessment include treatment-naïve men with intermediate- to high-risk localized prostate cancer who receive definitive therapy with EBRT plus CyberKnife SBRT boost.
Clinical Alternatives:
Prostate cancer treatment is guided by the initial disease risk category. Options can include active surveillance or watchful waiting; radical prostatectomy; EBRT using 3-dimensional conformal radiation therapy or intensitymodulated radiotherapy; HDR brachytherapy; high-intensity-focused ultrasound; hormonal therapy; cryosurgery; or combinations thereof.
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