Genitourinary Cancer

SAN DIEGO – Is there a future for prostate cancer chemoprevention?

"Some people think not," Maarten C. Bosland, Ph.D., said during a conference sponsored by the American Association for Cancer Research and the Prostate Cancer Foundation. "Maybe we should just engage in more exercise and decrease our body weight."

Population studies of people who move from low-risk to high-risk countries indicate that the risk of prostate cancer – including the risk of dying from the disease – could be modified by environmental factors that are not yet understood. However, the 5-alpha reductase inhibitor trials provided proof of principle that the risk of a subset of prostate cancer can be reduced by drugs. Why, then, has the prostate cancer prevention field not moved forward?

Reasons for the current stagnation of progress include failure of the Selenium and Vitamin E Cancer Prevention Trial (SELECT) to show preventive activity of selenium and vitamin E; the failure of a high-risk phase III study to show preventive activity of selenized yeast; the refusal of the Food and Drug Administration to approve finasteride for prostate cancer prevention, and uncertainty regarding the long-term effects of treatment with 5-alpha reductase inhibitors, according to Dr. Bosland of the department of pathology at the University of Illinois at Chicago.

Then there’s the issue of clinical or biologic significance.

"Some prostate cancers start early while others start late," he explained. "In each of these categories, some of the cancers can lead to death and others won’t; they’ll remain clinically insignificant. This poses a problem in thinking about how to go about chemoprevention. We want to prevent death from prostate cancer, but the window of opportunity in which we can intervene in a chemoprevention setting is limited, and it encompasses different stages of prostate cancer. This is difficult in terms of how we conduct clinical trials and identify endpoints that are meaningful in terms of preventing death from prostate cancer."

In the case of SELECT, investigators made a direct jump to a phase III study, based on evidence from clinical trials with prostate cancer as a secondary endpoint. "I think we should go back to the traditional approach, with phase I, II, and III trials [of candidate agents for prostate cancer chemoprevention]," Dr. Bosland said.

"There were no phase II studies to support phase III trials when SELECT and other studies with selenium were started." Clinical study "needs to be driven by the biology and mechanisms of prostate cancer," he said.

Speaking in the context of clinical studies, Dr. Bosland said that researchers are challenged by the fact that prostate cancer development is complicated by a range of different pathways and multiple underlying mechanisms. "That is consistent with the enormous heterogeneity of prostate cancer morphologically, genetically, and clinically," he said. "There are several types of prostate cancer with a different frequency, time of onset, and potential to progress. This means that we need a broad spectrum of chemoprevention agents or combination of agents. Multiple preclinical models are needed to represent the different pathways/types of cancer and progression to lethality. We need to focus on the ultimate goal of preventing only aggressive lethal cancer. We don’t want to interfere with clinically insignificant cancer. It’s meaningless."

To accomplish this, Dr. Bosland recommended the development of a valid high-throughput system to identify new candidate agents for prostate cancer chemoprevention. "Markers of fatal/lethal disease need to be identified for application in clinical trials," he continued. "A systematic evaluation of the predictive value of preclinical models, phase II designs, and biomarkers is also needed."

His other recommendations include: Conduct no phase III trials before having data from phase II trials, and conduct no phase II trials before having adequate preclinical data; consider the mechanism and biology of the agent and target before embarking on clinical studies; and develop a rational identification of candidate agents based on biology, mechanism, and results of high-throughput screening. "Only if we do all of this and find the funding for it will there be a future for prostate cancer chemoprevention," Dr.Bosland concluded.

Dr. Bosland said he had no relevant financial conflicts to disclose.

dbrunk@frontlinemedcom.com

SAN DIEGO – Is there a future for prostate cancer chemoprevention?

"Some people think not," Maarten C. Bosland, Ph.D., said during a conference sponsored by the American Association for Cancer Research and the Prostate Cancer Foundation. "Maybe we should just engage in more exercise and decrease our body weight."

Population studies of people who move from low-risk to high-risk countries indicate that the risk of prostate cancer – including the risk of dying from the disease – could be modified by environmental factors that are not yet understood. However, the 5-alpha reductase inhibitor trials provided proof of principle that the risk of a subset of prostate cancer can be reduced by drugs. Why, then, has the prostate cancer prevention field not moved forward?

Reasons for the current stagnation of progress include failure of the Selenium and Vitamin E Cancer Prevention Trial (SELECT) to show preventive activity of selenium and vitamin E; the failure of a high-risk phase III study to show preventive activity of selenized yeast; the refusal of the Food and Drug Administration to approve finasteride for prostate cancer prevention, and uncertainty regarding the long-term effects of treatment with 5-alpha reductase inhibitors, according to Dr. Bosland of the department of pathology at the University of Illinois at Chicago.

Then there’s the issue of clinical or biologic significance.

"Some prostate cancers start early while others start late," he explained. "In each of these categories, some of the cancers can lead to death and others won’t; they’ll remain clinically insignificant. This poses a problem in thinking about how to go about chemoprevention. We want to prevent death from prostate cancer, but the window of opportunity in which we can intervene in a chemoprevention setting is limited, and it encompasses different stages of prostate cancer. This is difficult in terms of how we conduct clinical trials and identify endpoints that are meaningful in terms of preventing death from prostate cancer."

In the case of SELECT, investigators made a direct jump to a phase III study, based on evidence from clinical trials with prostate cancer as a secondary endpoint. "I think we should go back to the traditional approach, with phase I, II, and III trials [of candidate agents for prostate cancer chemoprevention]," Dr. Bosland said.

"There were no phase II studies to support phase III trials when SELECT and other studies with selenium were started." Clinical study "needs to be driven by the biology and mechanisms of prostate cancer," he said.

Speaking in the context of clinical studies, Dr. Bosland said that researchers are challenged by the fact that prostate cancer development is complicated by a range of different pathways and multiple underlying mechanisms. "That is consistent with the enormous heterogeneity of prostate cancer morphologically, genetically, and clinically," he said. "There are several types of prostate cancer with a different frequency, time of onset, and potential to progress. This means that we need a broad spectrum of chemoprevention agents or combination of agents. Multiple preclinical models are needed to represent the different pathways/types of cancer and progression to lethality. We need to focus on the ultimate goal of preventing only aggressive lethal cancer. We don’t want to interfere with clinically insignificant cancer. It’s meaningless."

To accomplish this, Dr. Bosland recommended the development of a valid high-throughput system to identify new candidate agents for prostate cancer chemoprevention. "Markers of fatal/lethal disease need to be identified for application in clinical trials," he continued. "A systematic evaluation of the predictive value of preclinical models, phase II designs, and biomarkers is also needed."

His other recommendations include: Conduct no phase III trials before having data from phase II trials, and conduct no phase II trials before having adequate preclinical data; consider the mechanism and biology of the agent and target before embarking on clinical studies; and develop a rational identification of candidate agents based on biology, mechanism, and results of high-throughput screening. "Only if we do all of this and find the funding for it will there be a future for prostate cancer chemoprevention," Dr.Bosland concluded.

Dr. Bosland said he had no relevant financial conflicts to disclose.

dbrunk@frontlinemedcom.com

SAN DIEGO – Is there a future for prostate cancer chemoprevention?

"Some people think not," Maarten C. Bosland, Ph.D., said during a conference sponsored by the American Association for Cancer Research and the Prostate Cancer Foundation. "Maybe we should just engage in more exercise and decrease our body weight."

Population studies of people who move from low-risk to high-risk countries indicate that the risk of prostate cancer – including the risk of dying from the disease – could be modified by environmental factors that are not yet understood. However, the 5-alpha reductase inhibitor trials provided proof of principle that the risk of a subset of prostate cancer can be reduced by drugs. Why, then, has the prostate cancer prevention field not moved forward?

Reasons for the current stagnation of progress include failure of the Selenium and Vitamin E Cancer Prevention Trial (SELECT) to show preventive activity of selenium and vitamin E; the failure of a high-risk phase III study to show preventive activity of selenized yeast; the refusal of the Food and Drug Administration to approve finasteride for prostate cancer prevention, and uncertainty regarding the long-term effects of treatment with 5-alpha reductase inhibitors, according to Dr. Bosland of the department of pathology at the University of Illinois at Chicago.

Then there’s the issue of clinical or biologic significance.

"Some prostate cancers start early while others start late," he explained. "In each of these categories, some of the cancers can lead to death and others won’t; they’ll remain clinically insignificant. This poses a problem in thinking about how to go about chemoprevention. We want to prevent death from prostate cancer, but the window of opportunity in which we can intervene in a chemoprevention setting is limited, and it encompasses different stages of prostate cancer. This is difficult in terms of how we conduct clinical trials and identify endpoints that are meaningful in terms of preventing death from prostate cancer."

In the case of SELECT, investigators made a direct jump to a phase III study, based on evidence from clinical trials with prostate cancer as a secondary endpoint. "I think we should go back to the traditional approach, with phase I, II, and III trials [of candidate agents for prostate cancer chemoprevention]," Dr. Bosland said.

"There were no phase II studies to support phase III trials when SELECT and other studies with selenium were started." Clinical study "needs to be driven by the biology and mechanisms of prostate cancer," he said.

Speaking in the context of clinical studies, Dr. Bosland said that researchers are challenged by the fact that prostate cancer development is complicated by a range of different pathways and multiple underlying mechanisms. "That is consistent with the enormous heterogeneity of prostate cancer morphologically, genetically, and clinically," he said. "There are several types of prostate cancer with a different frequency, time of onset, and potential to progress. This means that we need a broad spectrum of chemoprevention agents or combination of agents. Multiple preclinical models are needed to represent the different pathways/types of cancer and progression to lethality. We need to focus on the ultimate goal of preventing only aggressive lethal cancer. We don’t want to interfere with clinically insignificant cancer. It’s meaningless."

To accomplish this, Dr. Bosland recommended the development of a valid high-throughput system to identify new candidate agents for prostate cancer chemoprevention. "Markers of fatal/lethal disease need to be identified for application in clinical trials," he continued. "A systematic evaluation of the predictive value of preclinical models, phase II designs, and biomarkers is also needed."

His other recommendations include: Conduct no phase III trials before having data from phase II trials, and conduct no phase II trials before having adequate preclinical data; consider the mechanism and biology of the agent and target before embarking on clinical studies; and develop a rational identification of candidate agents based on biology, mechanism, and results of high-throughput screening. "Only if we do all of this and find the funding for it will there be a future for prostate cancer chemoprevention," Dr.Bosland concluded.

Dr. Bosland said he had no relevant financial conflicts to disclose.

dbrunk@frontlinemedcom.com

Patients who undergo external beam radiation therapy for prostate cancer and smoke or have smoked have increased mortality and increased risk of complications, according to Dr. Emily Steinberger and her associates.

©Valeriy Kirsanov/fotolia.com

Current smoking significantly increased the risk of prostate-specific antigen relapse, distant metastases, and prostate cancer–related death. Current and former smokers were also at a higher risk of external beam radiation therapy–related genitourinary disorders. Smoking did not increase gastrointestinal toxicity, the researchers reported.

Oncologists should encourage patients to participate in smoking-cessation programs before therapy to potentially lower their risk, the researchers recommended.

Read the full article at BJU International (doi:10.1111/bju.12969).

Patients who undergo external beam radiation therapy for prostate cancer and smoke or have smoked have increased mortality and increased risk of complications, according to Dr. Emily Steinberger and her associates.

©Valeriy Kirsanov/fotolia.com

Current smoking significantly increased the risk of prostate-specific antigen relapse, distant metastases, and prostate cancer–related death. Current and former smokers were also at a higher risk of external beam radiation therapy–related genitourinary disorders. Smoking did not increase gastrointestinal toxicity, the researchers reported.

Oncologists should encourage patients to participate in smoking-cessation programs before therapy to potentially lower their risk, the researchers recommended.

Read the full article at BJU International (doi:10.1111/bju.12969).

Patients who undergo external beam radiation therapy for prostate cancer and smoke or have smoked have increased mortality and increased risk of complications, according to Dr. Emily Steinberger and her associates.

©Valeriy Kirsanov/fotolia.com

Current smoking significantly increased the risk of prostate-specific antigen relapse, distant metastases, and prostate cancer–related death. Current and former smokers were also at a higher risk of external beam radiation therapy–related genitourinary disorders. Smoking did not increase gastrointestinal toxicity, the researchers reported.

Oncologists should encourage patients to participate in smoking-cessation programs before therapy to potentially lower their risk, the researchers recommended.

Read the full article at BJU International (doi:10.1111/bju.12969).

SAN DIEGO – Long-term use of aspirin, other nonsteroidal anti-inflammatory drugs, or statins affected neither the levels of prostate-specific antigen nor the velocity with which those levels changed, judging from a secondary analysis from a clinical trial.

"The prevention of prostate cancer by statins, aspirin, and other NSAIDs is an important topic given the widespread use of these drugs in the general population and particularly in the population of men at risk for prostate cancer," Steven P. Stratton. Ph.D., said in an interview during a conference sponsored by the American Association for Cancer Research and the Prostate Cancer Foundation.

"A lot of scientific papers have been published linking these drugs together with cancer prevention, but results are controversial. So definitive, prospective studies in prostate cancer have to be performed before we can know for sure," he said.

In an effort to investigate the effect of these medications on markers used to assess prostate cancer risk, Dr. Stratton and his associates analyzed a population of 699 men enrolled in a phase III chemoprevention trial that was designed to investigate the effects of selenium supplementation on prostate cancer incidence.

"The selenium didn’t work, but we also asked men in this study about their use of other commonly used drugs like statins and NSAIDs; and we measured the PSA on all of these men every 6 months for 5 years," said Dr. Stratton, who chairs the Scientific Review Committee and leads the Prostate Cancer Prevention Team at the University of Arizona Cancer Center, Tucson. "We used statistical models to see if there were relationships between drug use and PSA changes over time."

Men in the study had a PSA greater than 4 ng/mL and/or a suspicious digital rectal examination and/or a PSA velocity (PSAV) of greater than 0.75 ng/mL/year, but with a negative prostate biopsy. During the course of the trial, 73 of the study participants were diagnosed with prostate cancer.

After Dr. Stratton and his associates adjusted for variables including selenium use, age, race, body mass index, and pack-years of smoking, they found that the use of aspirin, NSAIDs, or statins did not demonstrate significant associations with PSA (P = .79, .68, and .79, respectively) or PSAV (P = .23, .43, and .84, respectively). Stratification between men who developed prostate cancer during the course of the study and those with repeated negative prostate biopsies did not alter the results.

"The study wasn’t long enough, nor was it designed to detect a cancer prevention effect of these drugs, but we can say with pretty good confidence that the drug use did not impact the PSA test – a problem called ‘detection bias’ – given that we saw no differences between men taking the drugs and those who did not," Dr. Stratton said. "This is important, because if the drug interfered with the PSA test – regardless of the impact on cancer – it could reduce the usefulness of the PSA test in men taking these drugs."

He acknowledged certain limitations of the study, including the fact that it was a secondary analysis using data from a clinical trial designed for another purpose. "Also, the data on medication use were based on self-reporting by the patients rather than an examination of their medical records or more stringent methods of data collection," he said.

Dr. Stratton said he had no relevant financial conflicts to disclose.

dbrunk@frontlinemedcom.com

SAN DIEGO – Long-term use of aspirin, other nonsteroidal anti-inflammatory drugs, or statins affected neither the levels of prostate-specific antigen nor the velocity with which those levels changed, judging from a secondary analysis from a clinical trial.

"The prevention of prostate cancer by statins, aspirin, and other NSAIDs is an important topic given the widespread use of these drugs in the general population and particularly in the population of men at risk for prostate cancer," Steven P. Stratton. Ph.D., said in an interview during a conference sponsored by the American Association for Cancer Research and the Prostate Cancer Foundation.

"A lot of scientific papers have been published linking these drugs together with cancer prevention, but results are controversial. So definitive, prospective studies in prostate cancer have to be performed before we can know for sure," he said.

In an effort to investigate the effect of these medications on markers used to assess prostate cancer risk, Dr. Stratton and his associates analyzed a population of 699 men enrolled in a phase III chemoprevention trial that was designed to investigate the effects of selenium supplementation on prostate cancer incidence.

"The selenium didn’t work, but we also asked men in this study about their use of other commonly used drugs like statins and NSAIDs; and we measured the PSA on all of these men every 6 months for 5 years," said Dr. Stratton, who chairs the Scientific Review Committee and leads the Prostate Cancer Prevention Team at the University of Arizona Cancer Center, Tucson. "We used statistical models to see if there were relationships between drug use and PSA changes over time."

Men in the study had a PSA greater than 4 ng/mL and/or a suspicious digital rectal examination and/or a PSA velocity (PSAV) of greater than 0.75 ng/mL/year, but with a negative prostate biopsy. During the course of the trial, 73 of the study participants were diagnosed with prostate cancer.

After Dr. Stratton and his associates adjusted for variables including selenium use, age, race, body mass index, and pack-years of smoking, they found that the use of aspirin, NSAIDs, or statins did not demonstrate significant associations with PSA (P = .79, .68, and .79, respectively) or PSAV (P = .23, .43, and .84, respectively). Stratification between men who developed prostate cancer during the course of the study and those with repeated negative prostate biopsies did not alter the results.

"The study wasn’t long enough, nor was it designed to detect a cancer prevention effect of these drugs, but we can say with pretty good confidence that the drug use did not impact the PSA test – a problem called ‘detection bias’ – given that we saw no differences between men taking the drugs and those who did not," Dr. Stratton said. "This is important, because if the drug interfered with the PSA test – regardless of the impact on cancer – it could reduce the usefulness of the PSA test in men taking these drugs."

He acknowledged certain limitations of the study, including the fact that it was a secondary analysis using data from a clinical trial designed for another purpose. "Also, the data on medication use were based on self-reporting by the patients rather than an examination of their medical records or more stringent methods of data collection," he said.

Dr. Stratton said he had no relevant financial conflicts to disclose.

dbrunk@frontlinemedcom.com

SAN DIEGO – Long-term use of aspirin, other nonsteroidal anti-inflammatory drugs, or statins affected neither the levels of prostate-specific antigen nor the velocity with which those levels changed, judging from a secondary analysis from a clinical trial.

"The prevention of prostate cancer by statins, aspirin, and other NSAIDs is an important topic given the widespread use of these drugs in the general population and particularly in the population of men at risk for prostate cancer," Steven P. Stratton. Ph.D., said in an interview during a conference sponsored by the American Association for Cancer Research and the Prostate Cancer Foundation.

"A lot of scientific papers have been published linking these drugs together with cancer prevention, but results are controversial. So definitive, prospective studies in prostate cancer have to be performed before we can know for sure," he said.

In an effort to investigate the effect of these medications on markers used to assess prostate cancer risk, Dr. Stratton and his associates analyzed a population of 699 men enrolled in a phase III chemoprevention trial that was designed to investigate the effects of selenium supplementation on prostate cancer incidence.

"The selenium didn’t work, but we also asked men in this study about their use of other commonly used drugs like statins and NSAIDs; and we measured the PSA on all of these men every 6 months for 5 years," said Dr. Stratton, who chairs the Scientific Review Committee and leads the Prostate Cancer Prevention Team at the University of Arizona Cancer Center, Tucson. "We used statistical models to see if there were relationships between drug use and PSA changes over time."

Men in the study had a PSA greater than 4 ng/mL and/or a suspicious digital rectal examination and/or a PSA velocity (PSAV) of greater than 0.75 ng/mL/year, but with a negative prostate biopsy. During the course of the trial, 73 of the study participants were diagnosed with prostate cancer.

After Dr. Stratton and his associates adjusted for variables including selenium use, age, race, body mass index, and pack-years of smoking, they found that the use of aspirin, NSAIDs, or statins did not demonstrate significant associations with PSA (P = .79, .68, and .79, respectively) or PSAV (P = .23, .43, and .84, respectively). Stratification between men who developed prostate cancer during the course of the study and those with repeated negative prostate biopsies did not alter the results.

"The study wasn’t long enough, nor was it designed to detect a cancer prevention effect of these drugs, but we can say with pretty good confidence that the drug use did not impact the PSA test – a problem called ‘detection bias’ – given that we saw no differences between men taking the drugs and those who did not," Dr. Stratton said. "This is important, because if the drug interfered with the PSA test – regardless of the impact on cancer – it could reduce the usefulness of the PSA test in men taking these drugs."

He acknowledged certain limitations of the study, including the fact that it was a secondary analysis using data from a clinical trial designed for another purpose. "Also, the data on medication use were based on self-reporting by the patients rather than an examination of their medical records or more stringent methods of data collection," he said.

Dr. Stratton said he had no relevant financial conflicts to disclose.

dbrunk@frontlinemedcom.com

The use of statins following a prostate cancer diagnosis was associated with a decrease in all-cause and prostate cancer–related mortality risks in a large cohort of men from the United Kingdom.

The risk reduction was greatest among those who also used statins prior to their diagnosis, said Dr. Oriana Yu, of Jewish General Hospital, Montreal, and her colleagues.

The findings support experimental evidence suggesting a possible antitumor effect of statins on prostate carcinogenesis. Additional observational studies are needed to confirm the findings before a randomized controlled trial is launched to assess the effects of statins in the adjuvant setting, they said.

The study subjects were 11,722 men (mean age, 71.3 years) who were retrospectively identified from a large population-based electronic database. All were newly diagnosed as having nonmetastatic prostate cancer between April 1, 1998, and Dec. 31, 2009. During a mean follow-up of 4.4 years, 3,499 died, including 1,791 who died from prostate cancer.

Those who used statins after their prostate cancer diagnosis had a 24% decrease in the risk of prostate cancer mortality (hazard ratio, 0.76), and a 14% decrease in the risk of all-cause mortality (HR, 0.86). Statin use post diagnosis also was associated with a decreased risk of distant metastasis (HR, 0.77).

Among those who also used statins prior to their diagnosis, the corresponding hazard ratios for prostate cancer–related and all-cause mortalities were 0.55 and 0.66, compared with 0.82 and 0.91, respectively, for those who only used statins after diagnosis, the researchers reported (J. Clin Oncol. 2014; 32:5-11).

"A dose-response relationship was observed in terms of cumulative duration of use and dose, with the HRs becoming progressively more protective with longer durations of use and higher cumulative doses," they wrote.

For example, the adjusted hazard ratios for those using statins for less than 1 year and for those using statins for 3 or more years were 0.99 and 0.61, respectively. The adjusted hazard ratios for cumulative doses of less than 365 mg and 1,096 mg or more were 0.84 and 0.57, respectively.

Accumulating evidence suggests that statins have antitumor effects. Observational studies have looked at the association between statin use and prostate cancer outcomes, but the findings have been inconsistent, and none have specifically assessed whether prediagnosis use of statins modified the association seen between postdiagnosis use and outcomes, the investigators said.

The findings of an effect modification by prediagnostic use of statins in this study could be explained by several factors.

• Tumor characteristics may be more favorable in those using statins before diagnosis, resulting in improved prostate cancer outcomes, the investigators said. In the current study, however, those using statins before diagnosis were slightly more likely to have higher Gleason scores compared with nonusers.

• Duration of statin use is longest among those who used statins before their diagnosis, as in this study.

• Men who start statins before their prostate cancer diagnosis may differ from those who start after diagnosis. "Specifically, it is possible that the latter group required statins as a consequence of certain treatment, such as androgen deprivation therapy, which is known to increase lipid levels," and typically is prescribed to those with advanced prostate cancer, which would make statins seem to have more modest effects.

This study was supported by the Canadian Institutes of Health Research. Dr. Yu reported having no disclosures. One of her coauthors, Samy Suissa, Ph.D., reported serving as a consultant or adviser for AstraZeneca, Boehringer Ingelheim, and other companies.

The use of statins following a prostate cancer diagnosis was associated with a decrease in all-cause and prostate cancer–related mortality risks in a large cohort of men from the United Kingdom.

The risk reduction was greatest among those who also used statins prior to their diagnosis, said Dr. Oriana Yu, of Jewish General Hospital, Montreal, and her colleagues.

The findings support experimental evidence suggesting a possible antitumor effect of statins on prostate carcinogenesis. Additional observational studies are needed to confirm the findings before a randomized controlled trial is launched to assess the effects of statins in the adjuvant setting, they said.

The study subjects were 11,722 men (mean age, 71.3 years) who were retrospectively identified from a large population-based electronic database. All were newly diagnosed as having nonmetastatic prostate cancer between April 1, 1998, and Dec. 31, 2009. During a mean follow-up of 4.4 years, 3,499 died, including 1,791 who died from prostate cancer.

Those who used statins after their prostate cancer diagnosis had a 24% decrease in the risk of prostate cancer mortality (hazard ratio, 0.76), and a 14% decrease in the risk of all-cause mortality (HR, 0.86). Statin use post diagnosis also was associated with a decreased risk of distant metastasis (HR, 0.77).

Among those who also used statins prior to their diagnosis, the corresponding hazard ratios for prostate cancer–related and all-cause mortalities were 0.55 and 0.66, compared with 0.82 and 0.91, respectively, for those who only used statins after diagnosis, the researchers reported (J. Clin Oncol. 2014; 32:5-11).

"A dose-response relationship was observed in terms of cumulative duration of use and dose, with the HRs becoming progressively more protective with longer durations of use and higher cumulative doses," they wrote.

For example, the adjusted hazard ratios for those using statins for less than 1 year and for those using statins for 3 or more years were 0.99 and 0.61, respectively. The adjusted hazard ratios for cumulative doses of less than 365 mg and 1,096 mg or more were 0.84 and 0.57, respectively.

Accumulating evidence suggests that statins have antitumor effects. Observational studies have looked at the association between statin use and prostate cancer outcomes, but the findings have been inconsistent, and none have specifically assessed whether prediagnosis use of statins modified the association seen between postdiagnosis use and outcomes, the investigators said.

The findings of an effect modification by prediagnostic use of statins in this study could be explained by several factors.

• Tumor characteristics may be more favorable in those using statins before diagnosis, resulting in improved prostate cancer outcomes, the investigators said. In the current study, however, those using statins before diagnosis were slightly more likely to have higher Gleason scores compared with nonusers.

• Duration of statin use is longest among those who used statins before their diagnosis, as in this study.

• Men who start statins before their prostate cancer diagnosis may differ from those who start after diagnosis. "Specifically, it is possible that the latter group required statins as a consequence of certain treatment, such as androgen deprivation therapy, which is known to increase lipid levels," and typically is prescribed to those with advanced prostate cancer, which would make statins seem to have more modest effects.

This study was supported by the Canadian Institutes of Health Research. Dr. Yu reported having no disclosures. One of her coauthors, Samy Suissa, Ph.D., reported serving as a consultant or adviser for AstraZeneca, Boehringer Ingelheim, and other companies.

The use of statins following a prostate cancer diagnosis was associated with a decrease in all-cause and prostate cancer–related mortality risks in a large cohort of men from the United Kingdom.

The risk reduction was greatest among those who also used statins prior to their diagnosis, said Dr. Oriana Yu, of Jewish General Hospital, Montreal, and her colleagues.

The findings support experimental evidence suggesting a possible antitumor effect of statins on prostate carcinogenesis. Additional observational studies are needed to confirm the findings before a randomized controlled trial is launched to assess the effects of statins in the adjuvant setting, they said.

The study subjects were 11,722 men (mean age, 71.3 years) who were retrospectively identified from a large population-based electronic database. All were newly diagnosed as having nonmetastatic prostate cancer between April 1, 1998, and Dec. 31, 2009. During a mean follow-up of 4.4 years, 3,499 died, including 1,791 who died from prostate cancer.

Those who used statins after their prostate cancer diagnosis had a 24% decrease in the risk of prostate cancer mortality (hazard ratio, 0.76), and a 14% decrease in the risk of all-cause mortality (HR, 0.86). Statin use post diagnosis also was associated with a decreased risk of distant metastasis (HR, 0.77).

Among those who also used statins prior to their diagnosis, the corresponding hazard ratios for prostate cancer–related and all-cause mortalities were 0.55 and 0.66, compared with 0.82 and 0.91, respectively, for those who only used statins after diagnosis, the researchers reported (J. Clin Oncol. 2014; 32:5-11).

"A dose-response relationship was observed in terms of cumulative duration of use and dose, with the HRs becoming progressively more protective with longer durations of use and higher cumulative doses," they wrote.

For example, the adjusted hazard ratios for those using statins for less than 1 year and for those using statins for 3 or more years were 0.99 and 0.61, respectively. The adjusted hazard ratios for cumulative doses of less than 365 mg and 1,096 mg or more were 0.84 and 0.57, respectively.

Accumulating evidence suggests that statins have antitumor effects. Observational studies have looked at the association between statin use and prostate cancer outcomes, but the findings have been inconsistent, and none have specifically assessed whether prediagnosis use of statins modified the association seen between postdiagnosis use and outcomes, the investigators said.

The findings of an effect modification by prediagnostic use of statins in this study could be explained by several factors.

• Tumor characteristics may be more favorable in those using statins before diagnosis, resulting in improved prostate cancer outcomes, the investigators said. In the current study, however, those using statins before diagnosis were slightly more likely to have higher Gleason scores compared with nonusers.

• Duration of statin use is longest among those who used statins before their diagnosis, as in this study.

• Men who start statins before their prostate cancer diagnosis may differ from those who start after diagnosis. "Specifically, it is possible that the latter group required statins as a consequence of certain treatment, such as androgen deprivation therapy, which is known to increase lipid levels," and typically is prescribed to those with advanced prostate cancer, which would make statins seem to have more modest effects.

This study was supported by the Canadian Institutes of Health Research. Dr. Yu reported having no disclosures. One of her coauthors, Samy Suissa, Ph.D., reported serving as a consultant or adviser for AstraZeneca, Boehringer Ingelheim, and other companies.

The diagnosis of renal cell cancer in a patient aged 46 or younger should prompt a referral for germline mutation testing and genetic counseling, according to a report published online in the Journal of Clinical Oncology.

"Early" onset is a known clinical factor for hereditary renal cell cancer (RCC), but this study establishes a proposed age threshold for genetic testing. Dr. Brian Shuch and his associates at the National Cancer Institute analyzed 106,224 cases of RCC from the general U.S. population in the SEER-17 (Surveillance, Epidemiology, and End Results–17) database, as well as 608 cases of hereditary RCC in an NCI database. This represents the largest cohort of patients with hereditary RCC studied to date, the researchers noted.

The age of presentation for hereditary forms of RCC was consistently much younger – typically 27 years younger – than that for sporadic RCC. The median age of onset was 37 years and the mean age of onset was 39 years for hereditary RCC, compared with 63 and 64 years, respectively, for sporadic RCC.

The researchers found that using the 10th percentile of the typical age of onset in the general population – age 46 years or younger – made a practical cutoff point that yielded the most sensitive and specific criterion for recommending genetic testing and counseling.

Once a syndrome is identified, specific recommendations can be given regarding nephron-sparing surgery, partial nephrectomy, the timing of interventions, and surveillance of the renal mass, as well as for the screening of relatives, Dr. Shuch and his associates said (J. Clin. Oncol. 2013 Dec. 30 [doi:10.1200/JCO.2013.50.8192]).

The authors reported having no relevant financial disclosures.

The diagnosis of renal cell cancer in a patient aged 46 or younger should prompt a referral for germline mutation testing and genetic counseling, according to a report published online in the Journal of Clinical Oncology.

"Early" onset is a known clinical factor for hereditary renal cell cancer (RCC), but this study establishes a proposed age threshold for genetic testing. Dr. Brian Shuch and his associates at the National Cancer Institute analyzed 106,224 cases of RCC from the general U.S. population in the SEER-17 (Surveillance, Epidemiology, and End Results–17) database, as well as 608 cases of hereditary RCC in an NCI database. This represents the largest cohort of patients with hereditary RCC studied to date, the researchers noted.

The age of presentation for hereditary forms of RCC was consistently much younger – typically 27 years younger – than that for sporadic RCC. The median age of onset was 37 years and the mean age of onset was 39 years for hereditary RCC, compared with 63 and 64 years, respectively, for sporadic RCC.

The researchers found that using the 10th percentile of the typical age of onset in the general population – age 46 years or younger – made a practical cutoff point that yielded the most sensitive and specific criterion for recommending genetic testing and counseling.

Once a syndrome is identified, specific recommendations can be given regarding nephron-sparing surgery, partial nephrectomy, the timing of interventions, and surveillance of the renal mass, as well as for the screening of relatives, Dr. Shuch and his associates said (J. Clin. Oncol. 2013 Dec. 30 [doi:10.1200/JCO.2013.50.8192]).

The authors reported having no relevant financial disclosures.

The diagnosis of renal cell cancer in a patient aged 46 or younger should prompt a referral for germline mutation testing and genetic counseling, according to a report published online in the Journal of Clinical Oncology.

"Early" onset is a known clinical factor for hereditary renal cell cancer (RCC), but this study establishes a proposed age threshold for genetic testing. Dr. Brian Shuch and his associates at the National Cancer Institute analyzed 106,224 cases of RCC from the general U.S. population in the SEER-17 (Surveillance, Epidemiology, and End Results–17) database, as well as 608 cases of hereditary RCC in an NCI database. This represents the largest cohort of patients with hereditary RCC studied to date, the researchers noted.

The age of presentation for hereditary forms of RCC was consistently much younger – typically 27 years younger – than that for sporadic RCC. The median age of onset was 37 years and the mean age of onset was 39 years for hereditary RCC, compared with 63 and 64 years, respectively, for sporadic RCC.

The researchers found that using the 10th percentile of the typical age of onset in the general population – age 46 years or younger – made a practical cutoff point that yielded the most sensitive and specific criterion for recommending genetic testing and counseling.

Once a syndrome is identified, specific recommendations can be given regarding nephron-sparing surgery, partial nephrectomy, the timing of interventions, and surveillance of the renal mass, as well as for the screening of relatives, Dr. Shuch and his associates said (J. Clin. Oncol. 2013 Dec. 30 [doi:10.1200/JCO.2013.50.8192]).

The authors reported having no relevant financial disclosures.

Hypofractionation of intensity-modulated radiation therapy failed to reduce treatment failure rates in a study of 303 men with prostate cancer.

The combined biochemical and clinical failure rate was comparable between men randomly assigned to receive conventionally fractionated IMRT (76 Gy in 38 fractions of 2.0 Gy per fraction) and those assigned to receive hypofractionated IMRT (70.2 Gy in 26 fractions of 2.7 Gy per fraction), reported Dr. Alan Pollack, of the University of Miami, and his associates in the Journal of Clinical Oncology (2013 Oct. 7; published online ahead of print [doi: 10.1200/JCO.2013.51.1972]).

At the time the trial was designed, preliminary data indicated that hypofractionation (a higher radiation dose per fraction) carried a therapeutic advantage without increasing toxicity. The researchers estimated that by using hypofractionation, they would raise the cumulative dose from 76 Gy to the equivalent of 84.4 Gy, which they hoped would result in 15% fewer treatment failures.

The study subjects were men who had moderate- to high-risk prostate cancer. A total of 152 patients were randomly assigned to receive conventionally fractionated IMRT and 151 to receive hypofractionated IMRT. The two study groups were well balanced with regard to patient age, tumor T category and Gleason score, and initial prostate-specific antigen (PSA) level.

Men considered high risk received 2 years of androgen deprivation therapy; those at moderate risk received up to 4 months of androgen deprivation therapy. The proportion of patients in the moderate- and high-risk categories was similar between the two study groups.

At 5 years, biochemical and clinical failure rates did not differ significantly between the men who received conventionally fractionated IMRT (21.4%) and those who received hypofractionated IMRT (23.3%). These results were unchanged in two further analyses that used slightly different definitions of biochemical and clinical treatment failure, the investigators said.

Also, the two study groups did not differ in overall survival, prostate cancer–specific mortality, or rates of death from any cause.

Rates of local and distant treatment failure also were comparable: three cases of local failure and six of distant failure with conventionally fractionated IMRT, compared with five cases of local failure and eight of distant failure with hypofractionated IMRT.

Tumor T category, Gleason score, initial PSA level, and duration of androgen deprivation therapy were significant predictors of treatment failure. Treatment assignment was not a significant predictor of treatment failure.

The rates and severity of toxicity also were similar between the two study groups. Overall rates of gastrointestinal adverse events were comparable, as were the rates of each grade of severity of GI adverse events.

Rates of genitourinary dysfunction were high in both groups at baseline, mainly because many of the patients reported already having urinary frequency and urgency. Still, these rates increased substantially during follow-up in both groups. By the end of the study, 14.6% of men who received conventionally fractionated IMRT and 15.3% of those who received hypofractionated IMRT reported adverse genitourinary effects of grade 2 or higher.

Using a slightly different definition of genitourinary toxicity, the investigators found that 5-year cumulative risks of grade 2 or higher adverse effects were 37.9% for conventionally fractionated IMRT and 39.1% for hypofractionated IMRT, which also was not a significant difference.

This study was supported by the National Cancer Institute and Florida Biomed. Dr. Pollack and his associates reported ties to GE Healthcare, Calypso, and other companies.

Hypofractionation of intensity-modulated radiation therapy failed to reduce treatment failure rates in a study of 303 men with prostate cancer.

The combined biochemical and clinical failure rate was comparable between men randomly assigned to receive conventionally fractionated IMRT (76 Gy in 38 fractions of 2.0 Gy per fraction) and those assigned to receive hypofractionated IMRT (70.2 Gy in 26 fractions of 2.7 Gy per fraction), reported Dr. Alan Pollack, of the University of Miami, and his associates in the Journal of Clinical Oncology (2013 Oct. 7; published online ahead of print [doi: 10.1200/JCO.2013.51.1972]).

At the time the trial was designed, preliminary data indicated that hypofractionation (a higher radiation dose per fraction) carried a therapeutic advantage without increasing toxicity. The researchers estimated that by using hypofractionation, they would raise the cumulative dose from 76 Gy to the equivalent of 84.4 Gy, which they hoped would result in 15% fewer treatment failures.

The study subjects were men who had moderate- to high-risk prostate cancer. A total of 152 patients were randomly assigned to receive conventionally fractionated IMRT and 151 to receive hypofractionated IMRT. The two study groups were well balanced with regard to patient age, tumor T category and Gleason score, and initial prostate-specific antigen (PSA) level.

Men considered high risk received 2 years of androgen deprivation therapy; those at moderate risk received up to 4 months of androgen deprivation therapy. The proportion of patients in the moderate- and high-risk categories was similar between the two study groups.

At 5 years, biochemical and clinical failure rates did not differ significantly between the men who received conventionally fractionated IMRT (21.4%) and those who received hypofractionated IMRT (23.3%). These results were unchanged in two further analyses that used slightly different definitions of biochemical and clinical treatment failure, the investigators said.

Also, the two study groups did not differ in overall survival, prostate cancer–specific mortality, or rates of death from any cause.

Rates of local and distant treatment failure also were comparable: three cases of local failure and six of distant failure with conventionally fractionated IMRT, compared with five cases of local failure and eight of distant failure with hypofractionated IMRT.

Tumor T category, Gleason score, initial PSA level, and duration of androgen deprivation therapy were significant predictors of treatment failure. Treatment assignment was not a significant predictor of treatment failure.

The rates and severity of toxicity also were similar between the two study groups. Overall rates of gastrointestinal adverse events were comparable, as were the rates of each grade of severity of GI adverse events.

Rates of genitourinary dysfunction were high in both groups at baseline, mainly because many of the patients reported already having urinary frequency and urgency. Still, these rates increased substantially during follow-up in both groups. By the end of the study, 14.6% of men who received conventionally fractionated IMRT and 15.3% of those who received hypofractionated IMRT reported adverse genitourinary effects of grade 2 or higher.

Using a slightly different definition of genitourinary toxicity, the investigators found that 5-year cumulative risks of grade 2 or higher adverse effects were 37.9% for conventionally fractionated IMRT and 39.1% for hypofractionated IMRT, which also was not a significant difference.

This study was supported by the National Cancer Institute and Florida Biomed. Dr. Pollack and his associates reported ties to GE Healthcare, Calypso, and other companies.

Hypofractionation of intensity-modulated radiation therapy failed to reduce treatment failure rates in a study of 303 men with prostate cancer.

The combined biochemical and clinical failure rate was comparable between men randomly assigned to receive conventionally fractionated IMRT (76 Gy in 38 fractions of 2.0 Gy per fraction) and those assigned to receive hypofractionated IMRT (70.2 Gy in 26 fractions of 2.7 Gy per fraction), reported Dr. Alan Pollack, of the University of Miami, and his associates in the Journal of Clinical Oncology (2013 Oct. 7; published online ahead of print [doi: 10.1200/JCO.2013.51.1972]).

At the time the trial was designed, preliminary data indicated that hypofractionation (a higher radiation dose per fraction) carried a therapeutic advantage without increasing toxicity. The researchers estimated that by using hypofractionation, they would raise the cumulative dose from 76 Gy to the equivalent of 84.4 Gy, which they hoped would result in 15% fewer treatment failures.

The study subjects were men who had moderate- to high-risk prostate cancer. A total of 152 patients were randomly assigned to receive conventionally fractionated IMRT and 151 to receive hypofractionated IMRT. The two study groups were well balanced with regard to patient age, tumor T category and Gleason score, and initial prostate-specific antigen (PSA) level.

Men considered high risk received 2 years of androgen deprivation therapy; those at moderate risk received up to 4 months of androgen deprivation therapy. The proportion of patients in the moderate- and high-risk categories was similar between the two study groups.

At 5 years, biochemical and clinical failure rates did not differ significantly between the men who received conventionally fractionated IMRT (21.4%) and those who received hypofractionated IMRT (23.3%). These results were unchanged in two further analyses that used slightly different definitions of biochemical and clinical treatment failure, the investigators said.

Also, the two study groups did not differ in overall survival, prostate cancer–specific mortality, or rates of death from any cause.

Rates of local and distant treatment failure also were comparable: three cases of local failure and six of distant failure with conventionally fractionated IMRT, compared with five cases of local failure and eight of distant failure with hypofractionated IMRT.

Tumor T category, Gleason score, initial PSA level, and duration of androgen deprivation therapy were significant predictors of treatment failure. Treatment assignment was not a significant predictor of treatment failure.

The rates and severity of toxicity also were similar between the two study groups. Overall rates of gastrointestinal adverse events were comparable, as were the rates of each grade of severity of GI adverse events.

Rates of genitourinary dysfunction were high in both groups at baseline, mainly because many of the patients reported already having urinary frequency and urgency. Still, these rates increased substantially during follow-up in both groups. By the end of the study, 14.6% of men who received conventionally fractionated IMRT and 15.3% of those who received hypofractionated IMRT reported adverse genitourinary effects of grade 2 or higher.

Using a slightly different definition of genitourinary toxicity, the investigators found that 5-year cumulative risks of grade 2 or higher adverse effects were 37.9% for conventionally fractionated IMRT and 39.1% for hypofractionated IMRT, which also was not a significant difference.

This study was supported by the National Cancer Institute and Florida Biomed. Dr. Pollack and his associates reported ties to GE Healthcare, Calypso, and other companies.

A recommendation to consider the use of single-drug chemotherapy in most women with metastatic breast cancer is one of five newly recommended changes issued in the second round of the Choosing Wisely campaign.

The recommendations advise reconsidering tests and treatments that are often seen as routine, yet add costs without necessarily benefitting patients.

The action items are meant as a guide, not a demand, Dr. Lowell Schnipper said during a press briefing announcing the recommendations in advance of their release at a symposium on quality care sponsored by the American Society of Clinical Oncology.

"This is an attempt to encourage physicians and patients to curb the use of certain tests and procedures that are not supported by clinical research," said Dr. Schnipper, clinical director of Beth Israel Deaconess Medical Center Cancer Center in New York. "They are not meant to be legislative dictums. They are evidence-based suggestions presented as a foundation for discussion between doctor and patient – but there may be individual circumstances when they may decide to do otherwise."

The goal of the Choosing Wisely campaign – led by the American Board of Internal Medicine Foundation and joined by much of organized medicine – is to promote conversations that help patients and physicians choose care that is evidence driven, does not replicate care already provided, is free from harm, and is truly necessary.

ASCO’s second list of recommendations as part of the Choosing Wisely campaign includes the following:

• Restrict the use of antiemetic drugs to patients who are on chemotherapy regimens with a high risk of inducing nausea.

"One of the most important and unpleasant side effects of cancer drugs is nausea and vomiting," Dr. Schnipper said. "Over the years there has been an enormous degree of progress in medications to reduce and sometimes completely negate this."

But some of these drugs are "phenomenally expensive," he said. They should be saved for use in regimens that have a high potential to produce severe or persistent nausea and vomiting.

• Consider the use of single-drug chemotherapy in metastatic breast cancer.

"How much treatment is the optimal amount for metastatic breast cancer?" Dr. Schnipper said. "The concept is that more is better, but if we look at the outcomes for the majority of women, multiple drugs don’t add to survival and sometimes, because of the toxicities, actually detract from quality of life."

ASCO suggests that single drugs be used consecutively – a regimen that that may improve quality of life, even if it does not extend life. Multiple-drug regimens "should only be used in exceptional circumstances when a very rapid response to severe symptoms or life-threatening complications is at hand," according to the recommendation. "In a patient with advanced breast cancer who is not heavily pretreated and in whom symptomatic visceral crisis is apparent and rapid tumor response necessary, short courses of multiple agent
chemotherapy may be useful. However, as a general rule,
administration of sequential single agents lowers the risk of adverse
effects, may improve a patient’s quality of life, and does not typically
compromise overall survival.

• Avoid PET or PET-CT scans as part of routine follow-up care to monitor for recurrence in asymptomatic patients.

For patients who have completed treatment and show no clinical signs of relapse or new disease, routine imaging may not be necessary, Dr. Schnipper said.

"When we look too hard we almost always find some abnormality that, because of the patient’s medical history, we feel compelled to pursue. We don’t believe there’s any evidence showing that routine surveillance with CT or PET imaging provides anything that helps us keep patients alive longer. We think we can care for patients better with fewer risks, avoiding the cost of expensive imaging, and not compromising the cancer care they have received."

The report noted that "the utility of PET or PET-CT scanning for surveillance of both solid tumors and lymphomas remains unproven. In addition to clinical and economic considerations, the specter of unnecessary interventions and associated morbidity is a concern in the routine use of this technology for post-treatment surveillance."

• Avoid PSA testing in men who have a life expectancy of 10 years or less.

Again, the issue is whether any benefit of treatment would be worth the risk. "It’s not uncommon for these men to have comorbid illnesses that are more threatening than a low-grade prostate cancer. Most studies don’t show that treating affects mortality at all," although it can confer problems that really detract from quality of life.

Reserve targeted therapies intended for use against tumors with a specific genetic blueprint unless the patient’s tumor cells are expected to respond.

"These drugs are incredibly expensive," and there is no evidence that they are helpful in any but the rare cancers with specific biomarkers, Dr. Schnipper said.

"We can use biomarkers to identify patients who might have a good response – and also to identify patients who are not appropriate for these drugs," he said. "This is a good example of doing less while still maintaining a high quality of care."

Dr. Schnipper had no financial disclosures.

msullivan@frontlinemedcom.com

A recommendation to consider the use of single-drug chemotherapy in most women with metastatic breast cancer is one of five newly recommended changes issued in the second round of the Choosing Wisely campaign.

The recommendations advise reconsidering tests and treatments that are often seen as routine, yet add costs without necessarily benefitting patients.

The action items are meant as a guide, not a demand, Dr. Lowell Schnipper said during a press briefing announcing the recommendations in advance of their release at a symposium on quality care sponsored by the American Society of Clinical Oncology.

"This is an attempt to encourage physicians and patients to curb the use of certain tests and procedures that are not supported by clinical research," said Dr. Schnipper, clinical director of Beth Israel Deaconess Medical Center Cancer Center in New York. "They are not meant to be legislative dictums. They are evidence-based suggestions presented as a foundation for discussion between doctor and patient – but there may be individual circumstances when they may decide to do otherwise."

The goal of the Choosing Wisely campaign – led by the American Board of Internal Medicine Foundation and joined by much of organized medicine – is to promote conversations that help patients and physicians choose care that is evidence driven, does not replicate care already provided, is free from harm, and is truly necessary.

ASCO’s second list of recommendations as part of the Choosing Wisely campaign includes the following:

• Restrict the use of antiemetic drugs to patients who are on chemotherapy regimens with a high risk of inducing nausea.

"One of the most important and unpleasant side effects of cancer drugs is nausea and vomiting," Dr. Schnipper said. "Over the years there has been an enormous degree of progress in medications to reduce and sometimes completely negate this."

But some of these drugs are "phenomenally expensive," he said. They should be saved for use in regimens that have a high potential to produce severe or persistent nausea and vomiting.

• Consider the use of single-drug chemotherapy in metastatic breast cancer.

"How much treatment is the optimal amount for metastatic breast cancer?" Dr. Schnipper said. "The concept is that more is better, but if we look at the outcomes for the majority of women, multiple drugs don’t add to survival and sometimes, because of the toxicities, actually detract from quality of life."

ASCO suggests that single drugs be used consecutively – a regimen that that may improve quality of life, even if it does not extend life. Multiple-drug regimens "should only be used in exceptional circumstances when a very rapid response to severe symptoms or life-threatening complications is at hand," according to the recommendation. "In a patient with advanced breast cancer who is not heavily pretreated and in whom symptomatic visceral crisis is apparent and rapid tumor response necessary, short courses of multiple agent
chemotherapy may be useful. However, as a general rule,
administration of sequential single agents lowers the risk of adverse
effects, may improve a patient’s quality of life, and does not typically
compromise overall survival.

• Avoid PET or PET-CT scans as part of routine follow-up care to monitor for recurrence in asymptomatic patients.

For patients who have completed treatment and show no clinical signs of relapse or new disease, routine imaging may not be necessary, Dr. Schnipper said.

"When we look too hard we almost always find some abnormality that, because of the patient’s medical history, we feel compelled to pursue. We don’t believe there’s any evidence showing that routine surveillance with CT or PET imaging provides anything that helps us keep patients alive longer. We think we can care for patients better with fewer risks, avoiding the cost of expensive imaging, and not compromising the cancer care they have received."

The report noted that "the utility of PET or PET-CT scanning for surveillance of both solid tumors and lymphomas remains unproven. In addition to clinical and economic considerations, the specter of unnecessary interventions and associated morbidity is a concern in the routine use of this technology for post-treatment surveillance."

• Avoid PSA testing in men who have a life expectancy of 10 years or less.

Again, the issue is whether any benefit of treatment would be worth the risk. "It’s not uncommon for these men to have comorbid illnesses that are more threatening than a low-grade prostate cancer. Most studies don’t show that treating affects mortality at all," although it can confer problems that really detract from quality of life.

Reserve targeted therapies intended for use against tumors with a specific genetic blueprint unless the patient’s tumor cells are expected to respond.

"These drugs are incredibly expensive," and there is no evidence that they are helpful in any but the rare cancers with specific biomarkers, Dr. Schnipper said.

"We can use biomarkers to identify patients who might have a good response – and also to identify patients who are not appropriate for these drugs," he said. "This is a good example of doing less while still maintaining a high quality of care."

Dr. Schnipper had no financial disclosures.

msullivan@frontlinemedcom.com

A recommendation to consider the use of single-drug chemotherapy in most women with metastatic breast cancer is one of five newly recommended changes issued in the second round of the Choosing Wisely campaign.

The recommendations advise reconsidering tests and treatments that are often seen as routine, yet add costs without necessarily benefitting patients.

The action items are meant as a guide, not a demand, Dr. Lowell Schnipper said during a press briefing announcing the recommendations in advance of their release at a symposium on quality care sponsored by the American Society of Clinical Oncology.

"This is an attempt to encourage physicians and patients to curb the use of certain tests and procedures that are not supported by clinical research," said Dr. Schnipper, clinical director of Beth Israel Deaconess Medical Center Cancer Center in New York. "They are not meant to be legislative dictums. They are evidence-based suggestions presented as a foundation for discussion between doctor and patient – but there may be individual circumstances when they may decide to do otherwise."

The goal of the Choosing Wisely campaign – led by the American Board of Internal Medicine Foundation and joined by much of organized medicine – is to promote conversations that help patients and physicians choose care that is evidence driven, does not replicate care already provided, is free from harm, and is truly necessary.

ASCO’s second list of recommendations as part of the Choosing Wisely campaign includes the following:

• Restrict the use of antiemetic drugs to patients who are on chemotherapy regimens with a high risk of inducing nausea.

"One of the most important and unpleasant side effects of cancer drugs is nausea and vomiting," Dr. Schnipper said. "Over the years there has been an enormous degree of progress in medications to reduce and sometimes completely negate this."

But some of these drugs are "phenomenally expensive," he said. They should be saved for use in regimens that have a high potential to produce severe or persistent nausea and vomiting.

• Consider the use of single-drug chemotherapy in metastatic breast cancer.

"How much treatment is the optimal amount for metastatic breast cancer?" Dr. Schnipper said. "The concept is that more is better, but if we look at the outcomes for the majority of women, multiple drugs don’t add to survival and sometimes, because of the toxicities, actually detract from quality of life."

ASCO suggests that single drugs be used consecutively – a regimen that that may improve quality of life, even if it does not extend life. Multiple-drug regimens "should only be used in exceptional circumstances when a very rapid response to severe symptoms or life-threatening complications is at hand," according to the recommendation. "In a patient with advanced breast cancer who is not heavily pretreated and in whom symptomatic visceral crisis is apparent and rapid tumor response necessary, short courses of multiple agent
chemotherapy may be useful. However, as a general rule,
administration of sequential single agents lowers the risk of adverse
effects, may improve a patient’s quality of life, and does not typically
compromise overall survival.

• Avoid PET or PET-CT scans as part of routine follow-up care to monitor for recurrence in asymptomatic patients.

For patients who have completed treatment and show no clinical signs of relapse or new disease, routine imaging may not be necessary, Dr. Schnipper said.

"When we look too hard we almost always find some abnormality that, because of the patient’s medical history, we feel compelled to pursue. We don’t believe there’s any evidence showing that routine surveillance with CT or PET imaging provides anything that helps us keep patients alive longer. We think we can care for patients better with fewer risks, avoiding the cost of expensive imaging, and not compromising the cancer care they have received."

The report noted that "the utility of PET or PET-CT scanning for surveillance of both solid tumors and lymphomas remains unproven. In addition to clinical and economic considerations, the specter of unnecessary interventions and associated morbidity is a concern in the routine use of this technology for post-treatment surveillance."

• Avoid PSA testing in men who have a life expectancy of 10 years or less.

Again, the issue is whether any benefit of treatment would be worth the risk. "It’s not uncommon for these men to have comorbid illnesses that are more threatening than a low-grade prostate cancer. Most studies don’t show that treating affects mortality at all," although it can confer problems that really detract from quality of life.

Reserve targeted therapies intended for use against tumors with a specific genetic blueprint unless the patient’s tumor cells are expected to respond.

"These drugs are incredibly expensive," and there is no evidence that they are helpful in any but the rare cancers with specific biomarkers, Dr. Schnipper said.

"We can use biomarkers to identify patients who might have a good response – and also to identify patients who are not appropriate for these drugs," he said. "This is a good example of doing less while still maintaining a high quality of care."

Dr. Schnipper had no financial disclosures.

msullivan@frontlinemedcom.com

Urologists who incorporate intensity-modulated radiation therapy services into their own practices are much more likely to refer men with newly diagnosed nonmetastatic prostate cancer for IMRT than are other urologists, according to a report. The study was published online Oct. 23 in the New England Journal of Medicine.

Referral to an IMRT service in which the urologist holds a financial stake, also known as self-referral, is controversial because it poses a conflict of interest for the referring physician/investor or physician/owner. Yet many urologists have incorporated IMRT, which enjoys a high reimbursement rate, into their practices: An estimated 19% of urology practices in the United States included IMRT as of 2012, said Jean M. Mitchell, Ph.D., of Georgetown University, Washington.

The increase in IMRT has occurred "despite evidence that all treatments yield similar outcomes" for this type of cancer. "The findings raise concerns regarding the appropriate use of IMRT, especially among older Medicare beneficiaries, for whom the risks of undergoing intensive irradiation probably exceed the benefits," she said.

Dr. Mitchell compared the frequency of IMRT use in two analyses. In the first, she examined claims data for Medicare fee-for-service beneficiaries residing in 26 geographically dispersed states who were newly diagnosed as having nonmetastatic prostate cancer during a 5-year period, when many practices began offering their own IMRT services.

She then identified 35 self-referring urology practices in those states and matched them with an equal number of non–self-referring urology practices in the same area, which served as controls.

Dr. Mitchell found that among beneficiaries treated by self-referring urologists, the rate of IMRT referral increased by over 19%, from 13.1% to 32.3%, during the study period. In contrast, the rate of IMRT referral did not change in patients treated by non–self-referring urologists.

At the same time, the rates of use of two other treatments for noninvasive prostate cancer – brachytherapy and hormone use – fell by a combined 21% in the self-referring practices, she said (N. Engl. J. Med. 2013 Oct. 23 [doi:10.1056/NEJMsa1201141]).

In the second analysis, Dr. Mitchell assessed the records for urologists working at 11 self-referring private practices and urologists employed at 11 non–self-referring cancer centers participating in the National Comprehensive Cancer Network (NCCN) during the same time period. IMRT use by self-referring urologists increased from 9% to 42%, during the course of the study. Another 4.5% of men treated by self-referring urologists also obtained IMRT but attended a different provider to do so.

As in the other study, the corresponding rates of brachytherapy and hormone use in the self-referring practices dropped; in this case by 25%. Active surveillance decreased by 6% and the use of prostatectomy and other procedures declined by 4%.

"By contrast, there was virtually no change in the practice patterns of urologists employed by NCCN centers," where the rate of IMRT use held steady throughout the study period at approximately 8%.

"These findings are consistent with the results of other studies showing substantial increases in the frequency of use of advanced imaging techniques, clinical laboratory testing, and anatomical-pathology services by self-referring physicians," she said.

Financial incentives that may have contributed to the increased use of IMRT are clear. Marketing materials from one company that sells the technology to urologists claim that "treating 1.5 new patients monthly with IMRT could generate more than $425,000 in additional revenue per urologist annually," Dr. Mitchell said.

In some cases, the pressure to simply recoup the costs of investing in IMRT rather than to generate "extra" income may have contributed. Establishing IMRT in a urology practice, which includes hiring advanced support staff, can cost $2 million.

In other cases, "urologists may integrate IMRT into their practice because they believe this treatment will reduce the risk of adverse events and improve quality of life." However, the evidence shows that IMRT is no better than alternative treatments, and that each treatment offers pros and cons that affect quality of life, she added.

This study was funded by the American Society for Radiation Oncology and Georgetown University. Dr. Mitchell reported no financial conflicts of interest.

Urologists who incorporate intensity-modulated radiation therapy services into their own practices are much more likely to refer men with newly diagnosed nonmetastatic prostate cancer for IMRT than are other urologists, according to a report. The study was published online Oct. 23 in the New England Journal of Medicine.

Referral to an IMRT service in which the urologist holds a financial stake, also known as self-referral, is controversial because it poses a conflict of interest for the referring physician/investor or physician/owner. Yet many urologists have incorporated IMRT, which enjoys a high reimbursement rate, into their practices: An estimated 19% of urology practices in the United States included IMRT as of 2012, said Jean M. Mitchell, Ph.D., of Georgetown University, Washington.

The increase in IMRT has occurred "despite evidence that all treatments yield similar outcomes" for this type of cancer. "The findings raise concerns regarding the appropriate use of IMRT, especially among older Medicare beneficiaries, for whom the risks of undergoing intensive irradiation probably exceed the benefits," she said.

Dr. Mitchell compared the frequency of IMRT use in two analyses. In the first, she examined claims data for Medicare fee-for-service beneficiaries residing in 26 geographically dispersed states who were newly diagnosed as having nonmetastatic prostate cancer during a 5-year period, when many practices began offering their own IMRT services.

She then identified 35 self-referring urology practices in those states and matched them with an equal number of non–self-referring urology practices in the same area, which served as controls.

Dr. Mitchell found that among beneficiaries treated by self-referring urologists, the rate of IMRT referral increased by over 19%, from 13.1% to 32.3%, during the study period. In contrast, the rate of IMRT referral did not change in patients treated by non–self-referring urologists.

At the same time, the rates of use of two other treatments for noninvasive prostate cancer – brachytherapy and hormone use – fell by a combined 21% in the self-referring practices, she said (N. Engl. J. Med. 2013 Oct. 23 [doi:10.1056/NEJMsa1201141]).

In the second analysis, Dr. Mitchell assessed the records for urologists working at 11 self-referring private practices and urologists employed at 11 non–self-referring cancer centers participating in the National Comprehensive Cancer Network (NCCN) during the same time period. IMRT use by self-referring urologists increased from 9% to 42%, during the course of the study. Another 4.5% of men treated by self-referring urologists also obtained IMRT but attended a different provider to do so.

As in the other study, the corresponding rates of brachytherapy and hormone use in the self-referring practices dropped; in this case by 25%. Active surveillance decreased by 6% and the use of prostatectomy and other procedures declined by 4%.

"By contrast, there was virtually no change in the practice patterns of urologists employed by NCCN centers," where the rate of IMRT use held steady throughout the study period at approximately 8%.

"These findings are consistent with the results of other studies showing substantial increases in the frequency of use of advanced imaging techniques, clinical laboratory testing, and anatomical-pathology services by self-referring physicians," she said.

Financial incentives that may have contributed to the increased use of IMRT are clear. Marketing materials from one company that sells the technology to urologists claim that "treating 1.5 new patients monthly with IMRT could generate more than $425,000 in additional revenue per urologist annually," Dr. Mitchell said.

In some cases, the pressure to simply recoup the costs of investing in IMRT rather than to generate "extra" income may have contributed. Establishing IMRT in a urology practice, which includes hiring advanced support staff, can cost $2 million.

In other cases, "urologists may integrate IMRT into their practice because they believe this treatment will reduce the risk of adverse events and improve quality of life." However, the evidence shows that IMRT is no better than alternative treatments, and that each treatment offers pros and cons that affect quality of life, she added.

This study was funded by the American Society for Radiation Oncology and Georgetown University. Dr. Mitchell reported no financial conflicts of interest.

Urologists who incorporate intensity-modulated radiation therapy services into their own practices are much more likely to refer men with newly diagnosed nonmetastatic prostate cancer for IMRT than are other urologists, according to a report. The study was published online Oct. 23 in the New England Journal of Medicine.

Referral to an IMRT service in which the urologist holds a financial stake, also known as self-referral, is controversial because it poses a conflict of interest for the referring physician/investor or physician/owner. Yet many urologists have incorporated IMRT, which enjoys a high reimbursement rate, into their practices: An estimated 19% of urology practices in the United States included IMRT as of 2012, said Jean M. Mitchell, Ph.D., of Georgetown University, Washington.

The increase in IMRT has occurred "despite evidence that all treatments yield similar outcomes" for this type of cancer. "The findings raise concerns regarding the appropriate use of IMRT, especially among older Medicare beneficiaries, for whom the risks of undergoing intensive irradiation probably exceed the benefits," she said.

Dr. Mitchell compared the frequency of IMRT use in two analyses. In the first, she examined claims data for Medicare fee-for-service beneficiaries residing in 26 geographically dispersed states who were newly diagnosed as having nonmetastatic prostate cancer during a 5-year period, when many practices began offering their own IMRT services.

She then identified 35 self-referring urology practices in those states and matched them with an equal number of non–self-referring urology practices in the same area, which served as controls.

Dr. Mitchell found that among beneficiaries treated by self-referring urologists, the rate of IMRT referral increased by over 19%, from 13.1% to 32.3%, during the study period. In contrast, the rate of IMRT referral did not change in patients treated by non–self-referring urologists.

At the same time, the rates of use of two other treatments for noninvasive prostate cancer – brachytherapy and hormone use – fell by a combined 21% in the self-referring practices, she said (N. Engl. J. Med. 2013 Oct. 23 [doi:10.1056/NEJMsa1201141]).

In the second analysis, Dr. Mitchell assessed the records for urologists working at 11 self-referring private practices and urologists employed at 11 non–self-referring cancer centers participating in the National Comprehensive Cancer Network (NCCN) during the same time period. IMRT use by self-referring urologists increased from 9% to 42%, during the course of the study. Another 4.5% of men treated by self-referring urologists also obtained IMRT but attended a different provider to do so.

As in the other study, the corresponding rates of brachytherapy and hormone use in the self-referring practices dropped; in this case by 25%. Active surveillance decreased by 6% and the use of prostatectomy and other procedures declined by 4%.

"By contrast, there was virtually no change in the practice patterns of urologists employed by NCCN centers," where the rate of IMRT use held steady throughout the study period at approximately 8%.

"These findings are consistent with the results of other studies showing substantial increases in the frequency of use of advanced imaging techniques, clinical laboratory testing, and anatomical-pathology services by self-referring physicians," she said.

Financial incentives that may have contributed to the increased use of IMRT are clear. Marketing materials from one company that sells the technology to urologists claim that "treating 1.5 new patients monthly with IMRT could generate more than $425,000 in additional revenue per urologist annually," Dr. Mitchell said.

In some cases, the pressure to simply recoup the costs of investing in IMRT rather than to generate "extra" income may have contributed. Establishing IMRT in a urology practice, which includes hiring advanced support staff, can cost $2 million.

In other cases, "urologists may integrate IMRT into their practice because they believe this treatment will reduce the risk of adverse events and improve quality of life." However, the evidence shows that IMRT is no better than alternative treatments, and that each treatment offers pros and cons that affect quality of life, she added.

This study was funded by the American Society for Radiation Oncology and Georgetown University. Dr. Mitchell reported no financial conflicts of interest.

AMSTERDAM – Ipilimumab may be effective in castration-resistant prostate cancer if patients have a low burden of disease, based on phase III trial results reported at the multidisciplinary European cancer congresses.

In patients whose disease progressed within 6 months of docetaxel therapy, the primary endpoint of overall survival just missed reaching statistical significance in the CA184-043 trial at a median of 11.2 months in patients treated with ipilimumab (Yervoy) and of 10 months for those given placebo (hazard ratio [HR] = 0.85, P = .0053).

Sara Freeman/IMNG Medical Media

Overall survival at 1 year was 47% and 40% in each group, respectively, and 26% and 15% at 2 years.

Patients without visceral metastases were more likely to benefit than were those with visceral metastases, reported Dr. Winald Gerritsen of Radboud University Medical Center in Nijmegen, the Netherlands. The HR for overall survival according to the absence or presence of visceral metastases was 0.73.

Overall survival was better with ipilimumab in patients with an ECOG performance status of 0 rather than 1 (HR = 0.72), alkaline phosphatase levels less than 1.5 times the upper limit of normal rather than higher (HR = 0.78), hemoglobin levels of 11 g/dL rather than lower values (0.79), and normal rather than elevated lactate dehydrogenase levels (HR = 0.82).

Furthermore, an exploratory subgroup analysis showed a greater overall survival benefit for immunotherapy in patients with a better prognostic profile, based on alkaline phosphatase level, hemoglobin level, and the absence of visceral metastases. Overall survival was 22.7 months in these patients and 15.8 months for patients in the placebo group (HR = 0.62).

Progression-free survival was also significantly improved at 4 months for ipilimumab therapy and 3 months for placebo (HR = 0.70; P less than .0001). Further, a higher percentage of patients had a prostate-specific antigen response if they were given the immunotherapy (13.1% vs. 5.3%).

The CA184-043 study comprised 799 men with castration-resistant prostate cancer (CRPC) who had received prior chemotherapy with docetaxel but had signs of progression within 6 months of treatment. Subjects had to have one or more symptomatic bone metastases that could be irradiated with a single dose of radiotherapy (8 Gy). After irradiation, 399 men were randomized to receive ipilimumab at an intravenously infused dose of 10 mg/kg on weeks 1, 4, 7 and 10, and then every 12 weeks until progression or intolerable toxicity, and 400 men were randomized to receive a matching placebo.

Treatment-related adverse events occurred in 75% of those randomized to ipilimumab; 36% of the adverse events were grade 3 or higher. The corresponding percentages for those in the placebo arm were 45.5% and 10%. Grade 3 adverse events in the ipilimumab and placebo arms included gastrointestinal (18% vs. 0.8%), liver-related (4.6% vs. 1.3%), endocrine (2% vs. 0.5%), dermatologic (1% vs. 0%), and neurologic (0.3% vs. 0%).

There were 266 deaths in the active treatment arm and 304 in the placebo arm. Disease progression was the cause of death in 51.9% given active treatment and 61.4% given placebo. Toxicity due to ipilimumab was identified as a cause of death in 1% of patients.

The safety profile of ipilimumab in this study was consistent with that in previously defined adverse event profiles, Dr. Gerritsen maintained, and adverse events could usually be managed with standard management algorithms.

Discussant David Olmos of the Spanish National Cancer Research Centre in Madrid said that 19.8% in the treatment arm and 1.5% in the placebo arm discontinued treatment due to adverse events; 51% actually received four or more doses of the immunotherapy.

Sara Freeman/IMNG Medical Media

The postdocetaxel setting may not be the right one for testing the immunotherapy, he said. Tumor burden is related to the chances a vaccine treatment might work.

"Future trials should consider exploring the activity of a T-cell modulating agent in early settings of castration-resistant prostate cancer," Dr. Olmos proposed.

Ipilimumab 3 mg/kg monotherapy is currently licensed for the treatment of unresectable or metastatic melanoma in more than 40 countries. There are ongoing studies looking at its utility as an adjuvant treatment for melanoma and non–small-cell lung cancer, as well as an ongoing phase III trial in chemotherapy-naive CRPC.

The CA184-043 study was funded by Bristol-Myers Squibb. Dr. Gerritsen has participated in advisory boards for BMS, as well as other pharmaceutical companies, and received speaker’s fees from BMS, Astellas, and Jansen. Dr. Olmos has received speaker fees from Janssen-Cilag and Novartis, and consultant fees for advisory board participation from Janssen Diagnostic.

AMSTERDAM – Ipilimumab may be effective in castration-resistant prostate cancer if patients have a low burden of disease, based on phase III trial results reported at the multidisciplinary European cancer congresses.

In patients whose disease progressed within 6 months of docetaxel therapy, the primary endpoint of overall survival just missed reaching statistical significance in the CA184-043 trial at a median of 11.2 months in patients treated with ipilimumab (Yervoy) and of 10 months for those given placebo (hazard ratio [HR] = 0.85, P = .0053).

Sara Freeman/IMNG Medical Media

Overall survival at 1 year was 47% and 40% in each group, respectively, and 26% and 15% at 2 years.

Patients without visceral metastases were more likely to benefit than were those with visceral metastases, reported Dr. Winald Gerritsen of Radboud University Medical Center in Nijmegen, the Netherlands. The HR for overall survival according to the absence or presence of visceral metastases was 0.73.

Overall survival was better with ipilimumab in patients with an ECOG performance status of 0 rather than 1 (HR = 0.72), alkaline phosphatase levels less than 1.5 times the upper limit of normal rather than higher (HR = 0.78), hemoglobin levels of 11 g/dL rather than lower values (0.79), and normal rather than elevated lactate dehydrogenase levels (HR = 0.82).

Furthermore, an exploratory subgroup analysis showed a greater overall survival benefit for immunotherapy in patients with a better prognostic profile, based on alkaline phosphatase level, hemoglobin level, and the absence of visceral metastases. Overall survival was 22.7 months in these patients and 15.8 months for patients in the placebo group (HR = 0.62).

Progression-free survival was also significantly improved at 4 months for ipilimumab therapy and 3 months for placebo (HR = 0.70; P less than .0001). Further, a higher percentage of patients had a prostate-specific antigen response if they were given the immunotherapy (13.1% vs. 5.3%).

The CA184-043 study comprised 799 men with castration-resistant prostate cancer (CRPC) who had received prior chemotherapy with docetaxel but had signs of progression within 6 months of treatment. Subjects had to have one or more symptomatic bone metastases that could be irradiated with a single dose of radiotherapy (8 Gy). After irradiation, 399 men were randomized to receive ipilimumab at an intravenously infused dose of 10 mg/kg on weeks 1, 4, 7 and 10, and then every 12 weeks until progression or intolerable toxicity, and 400 men were randomized to receive a matching placebo.

Treatment-related adverse events occurred in 75% of those randomized to ipilimumab; 36% of the adverse events were grade 3 or higher. The corresponding percentages for those in the placebo arm were 45.5% and 10%. Grade 3 adverse events in the ipilimumab and placebo arms included gastrointestinal (18% vs. 0.8%), liver-related (4.6% vs. 1.3%), endocrine (2% vs. 0.5%), dermatologic (1% vs. 0%), and neurologic (0.3% vs. 0%).

There were 266 deaths in the active treatment arm and 304 in the placebo arm. Disease progression was the cause of death in 51.9% given active treatment and 61.4% given placebo. Toxicity due to ipilimumab was identified as a cause of death in 1% of patients.

The safety profile of ipilimumab in this study was consistent with that in previously defined adverse event profiles, Dr. Gerritsen maintained, and adverse events could usually be managed with standard management algorithms.

Discussant David Olmos of the Spanish National Cancer Research Centre in Madrid said that 19.8% in the treatment arm and 1.5% in the placebo arm discontinued treatment due to adverse events; 51% actually received four or more doses of the immunotherapy.

Sara Freeman/IMNG Medical Media

The postdocetaxel setting may not be the right one for testing the immunotherapy, he said. Tumor burden is related to the chances a vaccine treatment might work.

"Future trials should consider exploring the activity of a T-cell modulating agent in early settings of castration-resistant prostate cancer," Dr. Olmos proposed.

Ipilimumab 3 mg/kg monotherapy is currently licensed for the treatment of unresectable or metastatic melanoma in more than 40 countries. There are ongoing studies looking at its utility as an adjuvant treatment for melanoma and non–small-cell lung cancer, as well as an ongoing phase III trial in chemotherapy-naive CRPC.

The CA184-043 study was funded by Bristol-Myers Squibb. Dr. Gerritsen has participated in advisory boards for BMS, as well as other pharmaceutical companies, and received speaker’s fees from BMS, Astellas, and Jansen. Dr. Olmos has received speaker fees from Janssen-Cilag and Novartis, and consultant fees for advisory board participation from Janssen Diagnostic.

AMSTERDAM – Ipilimumab may be effective in castration-resistant prostate cancer if patients have a low burden of disease, based on phase III trial results reported at the multidisciplinary European cancer congresses.

In patients whose disease progressed within 6 months of docetaxel therapy, the primary endpoint of overall survival just missed reaching statistical significance in the CA184-043 trial at a median of 11.2 months in patients treated with ipilimumab (Yervoy) and of 10 months for those given placebo (hazard ratio [HR] = 0.85, P = .0053).

Sara Freeman/IMNG Medical Media

Overall survival at 1 year was 47% and 40% in each group, respectively, and 26% and 15% at 2 years.

Patients without visceral metastases were more likely to benefit than were those with visceral metastases, reported Dr. Winald Gerritsen of Radboud University Medical Center in Nijmegen, the Netherlands. The HR for overall survival according to the absence or presence of visceral metastases was 0.73.

Overall survival was better with ipilimumab in patients with an ECOG performance status of 0 rather than 1 (HR = 0.72), alkaline phosphatase levels less than 1.5 times the upper limit of normal rather than higher (HR = 0.78), hemoglobin levels of 11 g/dL rather than lower values (0.79), and normal rather than elevated lactate dehydrogenase levels (HR = 0.82).

Furthermore, an exploratory subgroup analysis showed a greater overall survival benefit for immunotherapy in patients with a better prognostic profile, based on alkaline phosphatase level, hemoglobin level, and the absence of visceral metastases. Overall survival was 22.7 months in these patients and 15.8 months for patients in the placebo group (HR = 0.62).

Progression-free survival was also significantly improved at 4 months for ipilimumab therapy and 3 months for placebo (HR = 0.70; P less than .0001). Further, a higher percentage of patients had a prostate-specific antigen response if they were given the immunotherapy (13.1% vs. 5.3%).

The CA184-043 study comprised 799 men with castration-resistant prostate cancer (CRPC) who had received prior chemotherapy with docetaxel but had signs of progression within 6 months of treatment. Subjects had to have one or more symptomatic bone metastases that could be irradiated with a single dose of radiotherapy (8 Gy). After irradiation, 399 men were randomized to receive ipilimumab at an intravenously infused dose of 10 mg/kg on weeks 1, 4, 7 and 10, and then every 12 weeks until progression or intolerable toxicity, and 400 men were randomized to receive a matching placebo.

Treatment-related adverse events occurred in 75% of those randomized to ipilimumab; 36% of the adverse events were grade 3 or higher. The corresponding percentages for those in the placebo arm were 45.5% and 10%. Grade 3 adverse events in the ipilimumab and placebo arms included gastrointestinal (18% vs. 0.8%), liver-related (4.6% vs. 1.3%), endocrine (2% vs. 0.5%), dermatologic (1% vs. 0%), and neurologic (0.3% vs. 0%).

There were 266 deaths in the active treatment arm and 304 in the placebo arm. Disease progression was the cause of death in 51.9% given active treatment and 61.4% given placebo. Toxicity due to ipilimumab was identified as a cause of death in 1% of patients.

The safety profile of ipilimumab in this study was consistent with that in previously defined adverse event profiles, Dr. Gerritsen maintained, and adverse events could usually be managed with standard management algorithms.

Discussant David Olmos of the Spanish National Cancer Research Centre in Madrid said that 19.8% in the treatment arm and 1.5% in the placebo arm discontinued treatment due to adverse events; 51% actually received four or more doses of the immunotherapy.

Sara Freeman/IMNG Medical Media

The postdocetaxel setting may not be the right one for testing the immunotherapy, he said. Tumor burden is related to the chances a vaccine treatment might work.

"Future trials should consider exploring the activity of a T-cell modulating agent in early settings of castration-resistant prostate cancer," Dr. Olmos proposed.

Ipilimumab 3 mg/kg monotherapy is currently licensed for the treatment of unresectable or metastatic melanoma in more than 40 countries. There are ongoing studies looking at its utility as an adjuvant treatment for melanoma and non–small-cell lung cancer, as well as an ongoing phase III trial in chemotherapy-naive CRPC.

The CA184-043 study was funded by Bristol-Myers Squibb. Dr. Gerritsen has participated in advisory boards for BMS, as well as other pharmaceutical companies, and received speaker’s fees from BMS, Astellas, and Jansen. Dr. Olmos has received speaker fees from Janssen-Cilag and Novartis, and consultant fees for advisory board participation from Janssen Diagnostic.

Physicians have not adopted single-fraction radiotherapy into routine practice for uncomplicated bone metastases of prostate cancer, as has been recommended, according to a report in the Oct. 9 issue of JAMA.

In a Research Letter to the editor, investigators reported that 3% of a series of 3,050 patients eligible for single-fraction palliative radiotherapy received it, even though this approach yields pain relief for bone metastases that is comparable to that of multiple-fraction radiotherapy.

Palliative radiotherapy, with either one or multiple fractions given daily, is the mainstay of treatment for painful bone metastases. Several trials have demonstrated that single-fraction and multiple-fraction approaches deliver the same pain relief, and single-fraction radiotherapy is significantly less expensive, said Dr. Justin E. Bekelman of the department of radiation oncology, University of Pennsylvania, Philadelphia, and his associates.

In addition, single-fraction radiotherapy has other patient-centric benefits, including improved quality of life, greater convenience, and reduced travel time. It is advocated over multiple-fraction radiotherapy by the Choosing Wisely campaign, they noted.

Dr. Bekelman and his colleagues analyzed information from the Surveillance, Epidemiology, and End Results database to assess whether single-fraction radiotherapy has been incorporated into routine clinical practice as recommended. They reviewed reimbursement records for Medicare beneficiaries with prostate cancer who were treated during a 3-year period.

The median patient age was 78 years, and 82% had two or more comorbid illnesses.

Of these patients, 3.3% received single-fraction radiotherapy, while the rest received multiple-fraction radiotherapy. Half of the patients received 10 or more fractions per day, the investigators said (JAMA 2013;310:1501-2).

In a sensitivity analysis restricted to the 2,028 patients who had no previous complicating events, 3.8% received single-fraction radiotherapy, confirming the results of the primary analysis.

The mean radiotherapy-related expenditures were 62% lower for patients who received single-fraction radiotherapy ($1,873), compared with those for patients who received multiple-fraction radiotherapy ($4,967).

This study was supported by the National Cancer Institute, the American Cancer Society, and the Leonard Davis Institute for Health Economics. No relevant financial conflicts of interest were reported.

TOR@frontlinemedcom.com

Physicians have not adopted single-fraction radiotherapy into routine practice for uncomplicated bone metastases of prostate cancer, as has been recommended, according to a report in the Oct. 9 issue of JAMA.

In a Research Letter to the editor, investigators reported that 3% of a series of 3,050 patients eligible for single-fraction palliative radiotherapy received it, even though this approach yields pain relief for bone metastases that is comparable to that of multiple-fraction radiotherapy.

Palliative radiotherapy, with either one or multiple fractions given daily, is the mainstay of treatment for painful bone metastases. Several trials have demonstrated that single-fraction and multiple-fraction approaches deliver the same pain relief, and single-fraction radiotherapy is significantly less expensive, said Dr. Justin E. Bekelman of the department of radiation oncology, University of Pennsylvania, Philadelphia, and his associates.

In addition, single-fraction radiotherapy has other patient-centric benefits, including improved quality of life, greater convenience, and reduced travel time. It is advocated over multiple-fraction radiotherapy by the Choosing Wisely campaign, they noted.

Dr. Bekelman and his colleagues analyzed information from the Surveillance, Epidemiology, and End Results database to assess whether single-fraction radiotherapy has been incorporated into routine clinical practice as recommended. They reviewed reimbursement records for Medicare beneficiaries with prostate cancer who were treated during a 3-year period.

The median patient age was 78 years, and 82% had two or more comorbid illnesses.

Of these patients, 3.3% received single-fraction radiotherapy, while the rest received multiple-fraction radiotherapy. Half of the patients received 10 or more fractions per day, the investigators said (JAMA 2013;310:1501-2).

In a sensitivity analysis restricted to the 2,028 patients who had no previous complicating events, 3.8% received single-fraction radiotherapy, confirming the results of the primary analysis.

The mean radiotherapy-related expenditures were 62% lower for patients who received single-fraction radiotherapy ($1,873), compared with those for patients who received multiple-fraction radiotherapy ($4,967).

This study was supported by the National Cancer Institute, the American Cancer Society, and the Leonard Davis Institute for Health Economics. No relevant financial conflicts of interest were reported.

TOR@frontlinemedcom.com

Physicians have not adopted single-fraction radiotherapy into routine practice for uncomplicated bone metastases of prostate cancer, as has been recommended, according to a report in the Oct. 9 issue of JAMA.

In a Research Letter to the editor, investigators reported that 3% of a series of 3,050 patients eligible for single-fraction palliative radiotherapy received it, even though this approach yields pain relief for bone metastases that is comparable to that of multiple-fraction radiotherapy.

Palliative radiotherapy, with either one or multiple fractions given daily, is the mainstay of treatment for painful bone metastases. Several trials have demonstrated that single-fraction and multiple-fraction approaches deliver the same pain relief, and single-fraction radiotherapy is significantly less expensive, said Dr. Justin E. Bekelman of the department of radiation oncology, University of Pennsylvania, Philadelphia, and his associates.

In addition, single-fraction radiotherapy has other patient-centric benefits, including improved quality of life, greater convenience, and reduced travel time. It is advocated over multiple-fraction radiotherapy by the Choosing Wisely campaign, they noted.

Dr. Bekelman and his colleagues analyzed information from the Surveillance, Epidemiology, and End Results database to assess whether single-fraction radiotherapy has been incorporated into routine clinical practice as recommended. They reviewed reimbursement records for Medicare beneficiaries with prostate cancer who were treated during a 3-year period.

The median patient age was 78 years, and 82% had two or more comorbid illnesses.

Of these patients, 3.3% received single-fraction radiotherapy, while the rest received multiple-fraction radiotherapy. Half of the patients received 10 or more fractions per day, the investigators said (JAMA 2013;310:1501-2).

In a sensitivity analysis restricted to the 2,028 patients who had no previous complicating events, 3.8% received single-fraction radiotherapy, confirming the results of the primary analysis.

The mean radiotherapy-related expenditures were 62% lower for patients who received single-fraction radiotherapy ($1,873), compared with those for patients who received multiple-fraction radiotherapy ($4,967).

This study was supported by the National Cancer Institute, the American Cancer Society, and the Leonard Davis Institute for Health Economics. No relevant financial conflicts of interest were reported.

TOR@frontlinemedcom.com