User login
Prostate cancer susceptibility loci identified
ORLANDO – , and captured an additional 6% of the familial relevant risk for prostate cancer.
In the Oncoarray stratified analysis, the researchers detected two single nucleotide polymorphisms (SNPs) that were associated with early-onset prostate cancer, defined as disease occurring in men younger than 55 years, and four that were associated with both aggressive and indolent disease.
“By the end of this year we will have a genetic test with 170 variants, and men at the top of 1% of risk group would have a 5.72% risk over the average man,” she said. “But if we incorporated in the rarer variants, which are associated with very nasty disease, could we then start to identify men who are at risk for aggressive disease, and if so, how should we intensively screen them or even treat them?”
Currently genome-wide association studies (GWAS) have identified over 100 prostate cancer susceptibility loci, which included 33% of the prostate cancer familial relative risk in Europeans.
“We already know how to stratify populations into risk groups,” said Dr. Eeles. “It is important for us to do the right tests to see if they are really going to help in terms of targeted screening.”
The heritability of prostate cancer is 57%, but currently there are no common aggressive-disease markers.
To identify further susceptibility variants, Dr. Eeles and her colleagues conducted a prostate cancer GWAS that was far larger than previous investigations. Their analysis included 46,939 prostate cancer cases and 27,910 controls of European ancestry who were genotyped using the 35,369 prostate cancer cases and 33,164 controls of European ancestry that were generated using other large-scale genotyping arrays.
Dr. Eeles explained that, because they want their data to be useful for future investigations and “you can’t type everything as just too expensive – there are millions of SNPs across the genome – we put in a GWAS backbone.”
What that means, she explained, is that, when these are typed, it can be inferred that the other genotypes are using mathematical modeling.
Their Oncoarray was a large sample consisting of various ethnic groups, but in this presentation Dr. Eeles focused on an analysis of 98.500 European samples. The number reached 145,000 because they combined it with previous results in a meta-analysis of samples derived from men of both European and Asian descent.
The identification of additional loci also will enable fine mapping efforts into the underlying biology of prostate cancer susceptibility, she added.
There was no funding source disclosed. Dr. Eeles has received honoraria from Janssen and Succinct Communications. Coauthor Peter Kraft reported a relationship with Merck, but none of the other investigators had any disclosures.
ORLANDO – , and captured an additional 6% of the familial relevant risk for prostate cancer.
In the Oncoarray stratified analysis, the researchers detected two single nucleotide polymorphisms (SNPs) that were associated with early-onset prostate cancer, defined as disease occurring in men younger than 55 years, and four that were associated with both aggressive and indolent disease.
“By the end of this year we will have a genetic test with 170 variants, and men at the top of 1% of risk group would have a 5.72% risk over the average man,” she said. “But if we incorporated in the rarer variants, which are associated with very nasty disease, could we then start to identify men who are at risk for aggressive disease, and if so, how should we intensively screen them or even treat them?”
Currently genome-wide association studies (GWAS) have identified over 100 prostate cancer susceptibility loci, which included 33% of the prostate cancer familial relative risk in Europeans.
“We already know how to stratify populations into risk groups,” said Dr. Eeles. “It is important for us to do the right tests to see if they are really going to help in terms of targeted screening.”
The heritability of prostate cancer is 57%, but currently there are no common aggressive-disease markers.
To identify further susceptibility variants, Dr. Eeles and her colleagues conducted a prostate cancer GWAS that was far larger than previous investigations. Their analysis included 46,939 prostate cancer cases and 27,910 controls of European ancestry who were genotyped using the 35,369 prostate cancer cases and 33,164 controls of European ancestry that were generated using other large-scale genotyping arrays.
Dr. Eeles explained that, because they want their data to be useful for future investigations and “you can’t type everything as just too expensive – there are millions of SNPs across the genome – we put in a GWAS backbone.”
What that means, she explained, is that, when these are typed, it can be inferred that the other genotypes are using mathematical modeling.
Their Oncoarray was a large sample consisting of various ethnic groups, but in this presentation Dr. Eeles focused on an analysis of 98.500 European samples. The number reached 145,000 because they combined it with previous results in a meta-analysis of samples derived from men of both European and Asian descent.
The identification of additional loci also will enable fine mapping efforts into the underlying biology of prostate cancer susceptibility, she added.
There was no funding source disclosed. Dr. Eeles has received honoraria from Janssen and Succinct Communications. Coauthor Peter Kraft reported a relationship with Merck, but none of the other investigators had any disclosures.
ORLANDO – , and captured an additional 6% of the familial relevant risk for prostate cancer.
In the Oncoarray stratified analysis, the researchers detected two single nucleotide polymorphisms (SNPs) that were associated with early-onset prostate cancer, defined as disease occurring in men younger than 55 years, and four that were associated with both aggressive and indolent disease.
“By the end of this year we will have a genetic test with 170 variants, and men at the top of 1% of risk group would have a 5.72% risk over the average man,” she said. “But if we incorporated in the rarer variants, which are associated with very nasty disease, could we then start to identify men who are at risk for aggressive disease, and if so, how should we intensively screen them or even treat them?”
Currently genome-wide association studies (GWAS) have identified over 100 prostate cancer susceptibility loci, which included 33% of the prostate cancer familial relative risk in Europeans.
“We already know how to stratify populations into risk groups,” said Dr. Eeles. “It is important for us to do the right tests to see if they are really going to help in terms of targeted screening.”
The heritability of prostate cancer is 57%, but currently there are no common aggressive-disease markers.
To identify further susceptibility variants, Dr. Eeles and her colleagues conducted a prostate cancer GWAS that was far larger than previous investigations. Their analysis included 46,939 prostate cancer cases and 27,910 controls of European ancestry who were genotyped using the 35,369 prostate cancer cases and 33,164 controls of European ancestry that were generated using other large-scale genotyping arrays.
Dr. Eeles explained that, because they want their data to be useful for future investigations and “you can’t type everything as just too expensive – there are millions of SNPs across the genome – we put in a GWAS backbone.”
What that means, she explained, is that, when these are typed, it can be inferred that the other genotypes are using mathematical modeling.
Their Oncoarray was a large sample consisting of various ethnic groups, but in this presentation Dr. Eeles focused on an analysis of 98.500 European samples. The number reached 145,000 because they combined it with previous results in a meta-analysis of samples derived from men of both European and Asian descent.
The identification of additional loci also will enable fine mapping efforts into the underlying biology of prostate cancer susceptibility, she added.
There was no funding source disclosed. Dr. Eeles has received honoraria from Janssen and Succinct Communications. Coauthor Peter Kraft reported a relationship with Merck, but none of the other investigators had any disclosures.
AT THE GENITOURINARY CANCERS SYMPOSIUM
Key clinical point: Findings demonstrate the utility of high-density arrays and large sample sizes for novel genetic discovery.
Major finding: A meta-analysis from more than 145,000 men identified 65 novel prostate cancer susceptibility loci.
Data source: A large genomic study conducted to identify prostate cancer susceptibility loci.
Disclosures: There was no funding source disclosed. Dr. Eeles has received honoraria from Janssen and Succinct Communications. Coauthor Peter Kraft reported a relationship with Merck, but none of the other investigators had any disclosures to report.
Clinical benefit persists for some with mRCC after stopping immune checkpoint blockade
ORLANDO – Some people with advanced kidney cancer who respond to immune checkpoint inhibitor therapy and subsequently stop because of immune-related adverse events may continue to see a clinical benefit for 6 months or longer, a retrospective, multicenter study reveals.
In fact, investigators labeled 42% of 19 patients with metastatic renal cell carcinoma (mRCC) “durable responders” to checkpoint inhibitor blockade. “What we’ve demonstrated is that, despite patients stopping their treatment, there is a subset who continue to have disease in check and controlled despite [their] not being on any therapy,” Rana R. McKay, MD, of the University of California, San Diego, said.
“Our subset was small, only 19 patients, so the next step is to validate our findings in larger study, and actually conduct a prospective trial to assess if discontinuation of therapy is worthwhile to investigate in this population,” Dr. McKay said during a press briefing prior to the Genitourinary Cancers Symposium sponsored by the American Society of Clinical Oncology, ASTRO, and the Society of Urologic Oncology.
PD-1/PDL-1 inhibitors demonstrate efficacy against an expanding list of malignancies, Dr. McKay said. The current standard is to administer these agents on a continuous basis until cancer progression or toxicity occurs. However, the study raises the possibility of intentionally discontinuing their use in some patients in the future, primarily because PD-1/PD-L1 inhibitors are associated with a wide range of side effects. Most concerning are immune-related adverse events “which are thought to be due to immune system activation,” she said.
“These drugs work to reinvigorate the immune response, and one of the unintended consequences is … they may also elicit an autoimmune response against one or more organs in the body,” said Sumanta Pal, MD, of City of Hope Medical Center in Duarte, Calif. and moderator of the press briefing.
“There was a wide spectrum of adverse events affecting different organ systems,” Dr. McKay said, “including pneumonitis, myositis, nephritis, hepatitis, pericarditis, and myocarditis, just to name a few.” A total of 84% of patients required steroids to treat immune-related adverse events, 11% needed additional immunosuppressant agents to treat their symptoms, and 53% have ongoing toxicity.
“If a patient has immune-related side effects, the impact can be serious,” Dr. Pal said. “This [study] certainly supports the premise that those individuals who experience immune related side effects could have a tangible benefit from the drug nonetheless.”
Median patient age was 68 years, 74% were male and 26% had aggressive disease. In the durable responders group, the median time on treatment was 11 months and median time off treatment was 20 months. In contrast, the patients whose cancer worsened immediately after therapy cessation were treated a median 4 months and were off treatment a median of only 2 months. A total of 63% received either PD-1 or PD-L1 monotherapy and the remainder received one of these inhibitors in combination with other systemic therapies.
Prospective studies are warranted to determine approaches to customize immunotherapy based on response, Dr. McKay said. A phase II study is planned to assess optimized management of nivolumab therapy based on response in patients with mRCC, she added
ORLANDO – Some people with advanced kidney cancer who respond to immune checkpoint inhibitor therapy and subsequently stop because of immune-related adverse events may continue to see a clinical benefit for 6 months or longer, a retrospective, multicenter study reveals.
In fact, investigators labeled 42% of 19 patients with metastatic renal cell carcinoma (mRCC) “durable responders” to checkpoint inhibitor blockade. “What we’ve demonstrated is that, despite patients stopping their treatment, there is a subset who continue to have disease in check and controlled despite [their] not being on any therapy,” Rana R. McKay, MD, of the University of California, San Diego, said.
“Our subset was small, only 19 patients, so the next step is to validate our findings in larger study, and actually conduct a prospective trial to assess if discontinuation of therapy is worthwhile to investigate in this population,” Dr. McKay said during a press briefing prior to the Genitourinary Cancers Symposium sponsored by the American Society of Clinical Oncology, ASTRO, and the Society of Urologic Oncology.
PD-1/PDL-1 inhibitors demonstrate efficacy against an expanding list of malignancies, Dr. McKay said. The current standard is to administer these agents on a continuous basis until cancer progression or toxicity occurs. However, the study raises the possibility of intentionally discontinuing their use in some patients in the future, primarily because PD-1/PD-L1 inhibitors are associated with a wide range of side effects. Most concerning are immune-related adverse events “which are thought to be due to immune system activation,” she said.
“These drugs work to reinvigorate the immune response, and one of the unintended consequences is … they may also elicit an autoimmune response against one or more organs in the body,” said Sumanta Pal, MD, of City of Hope Medical Center in Duarte, Calif. and moderator of the press briefing.
“There was a wide spectrum of adverse events affecting different organ systems,” Dr. McKay said, “including pneumonitis, myositis, nephritis, hepatitis, pericarditis, and myocarditis, just to name a few.” A total of 84% of patients required steroids to treat immune-related adverse events, 11% needed additional immunosuppressant agents to treat their symptoms, and 53% have ongoing toxicity.
“If a patient has immune-related side effects, the impact can be serious,” Dr. Pal said. “This [study] certainly supports the premise that those individuals who experience immune related side effects could have a tangible benefit from the drug nonetheless.”
Median patient age was 68 years, 74% were male and 26% had aggressive disease. In the durable responders group, the median time on treatment was 11 months and median time off treatment was 20 months. In contrast, the patients whose cancer worsened immediately after therapy cessation were treated a median 4 months and were off treatment a median of only 2 months. A total of 63% received either PD-1 or PD-L1 monotherapy and the remainder received one of these inhibitors in combination with other systemic therapies.
Prospective studies are warranted to determine approaches to customize immunotherapy based on response, Dr. McKay said. A phase II study is planned to assess optimized management of nivolumab therapy based on response in patients with mRCC, she added
ORLANDO – Some people with advanced kidney cancer who respond to immune checkpoint inhibitor therapy and subsequently stop because of immune-related adverse events may continue to see a clinical benefit for 6 months or longer, a retrospective, multicenter study reveals.
In fact, investigators labeled 42% of 19 patients with metastatic renal cell carcinoma (mRCC) “durable responders” to checkpoint inhibitor blockade. “What we’ve demonstrated is that, despite patients stopping their treatment, there is a subset who continue to have disease in check and controlled despite [their] not being on any therapy,” Rana R. McKay, MD, of the University of California, San Diego, said.
“Our subset was small, only 19 patients, so the next step is to validate our findings in larger study, and actually conduct a prospective trial to assess if discontinuation of therapy is worthwhile to investigate in this population,” Dr. McKay said during a press briefing prior to the Genitourinary Cancers Symposium sponsored by the American Society of Clinical Oncology, ASTRO, and the Society of Urologic Oncology.
PD-1/PDL-1 inhibitors demonstrate efficacy against an expanding list of malignancies, Dr. McKay said. The current standard is to administer these agents on a continuous basis until cancer progression or toxicity occurs. However, the study raises the possibility of intentionally discontinuing their use in some patients in the future, primarily because PD-1/PD-L1 inhibitors are associated with a wide range of side effects. Most concerning are immune-related adverse events “which are thought to be due to immune system activation,” she said.
“These drugs work to reinvigorate the immune response, and one of the unintended consequences is … they may also elicit an autoimmune response against one or more organs in the body,” said Sumanta Pal, MD, of City of Hope Medical Center in Duarte, Calif. and moderator of the press briefing.
“There was a wide spectrum of adverse events affecting different organ systems,” Dr. McKay said, “including pneumonitis, myositis, nephritis, hepatitis, pericarditis, and myocarditis, just to name a few.” A total of 84% of patients required steroids to treat immune-related adverse events, 11% needed additional immunosuppressant agents to treat their symptoms, and 53% have ongoing toxicity.
“If a patient has immune-related side effects, the impact can be serious,” Dr. Pal said. “This [study] certainly supports the premise that those individuals who experience immune related side effects could have a tangible benefit from the drug nonetheless.”
Median patient age was 68 years, 74% were male and 26% had aggressive disease. In the durable responders group, the median time on treatment was 11 months and median time off treatment was 20 months. In contrast, the patients whose cancer worsened immediately after therapy cessation were treated a median 4 months and were off treatment a median of only 2 months. A total of 63% received either PD-1 or PD-L1 monotherapy and the remainder received one of these inhibitors in combination with other systemic therapies.
Prospective studies are warranted to determine approaches to customize immunotherapy based on response, Dr. McKay said. A phase II study is planned to assess optimized management of nivolumab therapy based on response in patients with mRCC, she added
Key clinical point: A subset of patients with metastatic renal cell carcinoma see a durable benefit after stopping therapy with immune checkpoint inhibitors due to immune related adverse events.
Major finding: Just over 40% of patients experienced a durable response to therapy of 6 months or longer after stopping therapy with an immune checkpoint inhibitor.
Data source: Retrospective study of 19 patients conducted at five academic medical centers.
Disclosures: The Dana-Farber/Harvard Cancer Center Kidney SPORE, and the Trust Family, Michael Brigham, and Loker Pin funded this study. Rana R. McKay, MD, receives institutional research funding from Pfizer and Bayer.
Antibiotic use may hamper checkpoint inhibitors for mRCC
Antibiotics may hamper the effectiveness of immune checkpoint inhibitors for patients with metastatic renal cell carcinoma, according to a small, retrospective study. Using antibiotics within 1 month of starting a checkpoint inhibitor was associated with significantly shorter progression-free survival, as well as a trend toward shorter overall survival, in a study of 80 patients with metastatic renal cell carcinoma.
Although the mechanism remains unknown, the prevailing theory is that antibiotics adversely alter the composition of the gut microbiome, and in so doing, slash the ability of beneficial bacteria to boost efficacy of immune checkpoint blockade.
“The data I presented today are just preliminary. But the results are really important because there is a kind of connection between the microbiome, antibiotics, and immune checkpoint blockade,” Lisa Derosa, MD, of Paris-Sud University, Villejuif, France, said during a press briefing prior to the 2017 genitourinary cancers symposium sponsored by the American Society of Clinical Oncology, ASTRO, and the Society of Urologic Oncology.
Dr. Derosa and her colleagues retrospectively assessed 80 people with metastatic renal cell carcinoma enrolled in prospective trials at Gustave Roussy Cancer Institute. The patients were treated with the PD1/PD-L1 inhibitors alone or in combination. The researchers compared survival of 16 patients who also received broad-spectrum antibiotic therapy within 1 month of their first dose of immunotherapy with 64 others who did not receive antibiotics.
Progression-free survival was significantly shorter for patients in the antibiotic group, 2.3 months versus 8.1 months for the nonantibiotic group (P less than .001) on Kaplan-Meier curves. The statistical significance persisted even after the researchers controlled for age, gender, International Metastatic Renal-Cell Carcinoma Database Consortium (IMDC) risk classification, tumor burden, and PPI use in a multivariate analysis. Similarly, the objective response rate to checkpoint inhibition therapy was significantly lower among patients in the antibiotic group (P less than .002).
“There was no significant difference, however, between these groups in overall survival,” Dr. Derosa said.
Despite the findings, Dr. Derosa said it’s too soon to say antibiotics are contraindicated in this patient population. “It may be important to pay attention to these antibiotics in patients treated with immune response inhibitors, but the data are still preliminary.”
“I would propose this data is very intriguing, but it was retrospectively generated, so I consider it hypothesis-generating,” said Sumanta Pal, MD, of City of Hope Medical Center in Duarte, Calif., and moderator of the press briefing. “One has to consider the fact that antibiotics are used under circumstances of medical necessity. I wouldn’t forgo treatment of any active infection … I would use as medically necessary.”
Beta-lactamases and fluoroquinolones comprised the majority of antibiotics in the study. The majority, 67 patients, received immune monotherapy with single-agent PD-1 or PD-L1 inhibitors. Another 10 patients received a combination of a PD-1 inhibitor and a CTLA-4 inhibitor, and 3 were treated with a PD-L1 inhibitor and bevacizumab.
“This is the first analysis evaluating impact of antibiotics on outcome of advanced renal carcinoma patients treated in the era of immune checkpoint blockade,” Dr. Derosa said. “We have a lot of work to do.” She and her colleagues plan to continue enrolling patients in the study. They also plan to evaluate whether alteration of the microbiome composition does play a role in diminishing the effectiveness of immunotherapy, and if so, which types of bacteria are the most likely culprits.
Antibiotics may hamper the effectiveness of immune checkpoint inhibitors for patients with metastatic renal cell carcinoma, according to a small, retrospective study. Using antibiotics within 1 month of starting a checkpoint inhibitor was associated with significantly shorter progression-free survival, as well as a trend toward shorter overall survival, in a study of 80 patients with metastatic renal cell carcinoma.
Although the mechanism remains unknown, the prevailing theory is that antibiotics adversely alter the composition of the gut microbiome, and in so doing, slash the ability of beneficial bacteria to boost efficacy of immune checkpoint blockade.
“The data I presented today are just preliminary. But the results are really important because there is a kind of connection between the microbiome, antibiotics, and immune checkpoint blockade,” Lisa Derosa, MD, of Paris-Sud University, Villejuif, France, said during a press briefing prior to the 2017 genitourinary cancers symposium sponsored by the American Society of Clinical Oncology, ASTRO, and the Society of Urologic Oncology.
Dr. Derosa and her colleagues retrospectively assessed 80 people with metastatic renal cell carcinoma enrolled in prospective trials at Gustave Roussy Cancer Institute. The patients were treated with the PD1/PD-L1 inhibitors alone or in combination. The researchers compared survival of 16 patients who also received broad-spectrum antibiotic therapy within 1 month of their first dose of immunotherapy with 64 others who did not receive antibiotics.
Progression-free survival was significantly shorter for patients in the antibiotic group, 2.3 months versus 8.1 months for the nonantibiotic group (P less than .001) on Kaplan-Meier curves. The statistical significance persisted even after the researchers controlled for age, gender, International Metastatic Renal-Cell Carcinoma Database Consortium (IMDC) risk classification, tumor burden, and PPI use in a multivariate analysis. Similarly, the objective response rate to checkpoint inhibition therapy was significantly lower among patients in the antibiotic group (P less than .002).
“There was no significant difference, however, between these groups in overall survival,” Dr. Derosa said.
Despite the findings, Dr. Derosa said it’s too soon to say antibiotics are contraindicated in this patient population. “It may be important to pay attention to these antibiotics in patients treated with immune response inhibitors, but the data are still preliminary.”
“I would propose this data is very intriguing, but it was retrospectively generated, so I consider it hypothesis-generating,” said Sumanta Pal, MD, of City of Hope Medical Center in Duarte, Calif., and moderator of the press briefing. “One has to consider the fact that antibiotics are used under circumstances of medical necessity. I wouldn’t forgo treatment of any active infection … I would use as medically necessary.”
Beta-lactamases and fluoroquinolones comprised the majority of antibiotics in the study. The majority, 67 patients, received immune monotherapy with single-agent PD-1 or PD-L1 inhibitors. Another 10 patients received a combination of a PD-1 inhibitor and a CTLA-4 inhibitor, and 3 were treated with a PD-L1 inhibitor and bevacizumab.
“This is the first analysis evaluating impact of antibiotics on outcome of advanced renal carcinoma patients treated in the era of immune checkpoint blockade,” Dr. Derosa said. “We have a lot of work to do.” She and her colleagues plan to continue enrolling patients in the study. They also plan to evaluate whether alteration of the microbiome composition does play a role in diminishing the effectiveness of immunotherapy, and if so, which types of bacteria are the most likely culprits.
Antibiotics may hamper the effectiveness of immune checkpoint inhibitors for patients with metastatic renal cell carcinoma, according to a small, retrospective study. Using antibiotics within 1 month of starting a checkpoint inhibitor was associated with significantly shorter progression-free survival, as well as a trend toward shorter overall survival, in a study of 80 patients with metastatic renal cell carcinoma.
Although the mechanism remains unknown, the prevailing theory is that antibiotics adversely alter the composition of the gut microbiome, and in so doing, slash the ability of beneficial bacteria to boost efficacy of immune checkpoint blockade.
“The data I presented today are just preliminary. But the results are really important because there is a kind of connection between the microbiome, antibiotics, and immune checkpoint blockade,” Lisa Derosa, MD, of Paris-Sud University, Villejuif, France, said during a press briefing prior to the 2017 genitourinary cancers symposium sponsored by the American Society of Clinical Oncology, ASTRO, and the Society of Urologic Oncology.
Dr. Derosa and her colleagues retrospectively assessed 80 people with metastatic renal cell carcinoma enrolled in prospective trials at Gustave Roussy Cancer Institute. The patients were treated with the PD1/PD-L1 inhibitors alone or in combination. The researchers compared survival of 16 patients who also received broad-spectrum antibiotic therapy within 1 month of their first dose of immunotherapy with 64 others who did not receive antibiotics.
Progression-free survival was significantly shorter for patients in the antibiotic group, 2.3 months versus 8.1 months for the nonantibiotic group (P less than .001) on Kaplan-Meier curves. The statistical significance persisted even after the researchers controlled for age, gender, International Metastatic Renal-Cell Carcinoma Database Consortium (IMDC) risk classification, tumor burden, and PPI use in a multivariate analysis. Similarly, the objective response rate to checkpoint inhibition therapy was significantly lower among patients in the antibiotic group (P less than .002).
“There was no significant difference, however, between these groups in overall survival,” Dr. Derosa said.
Despite the findings, Dr. Derosa said it’s too soon to say antibiotics are contraindicated in this patient population. “It may be important to pay attention to these antibiotics in patients treated with immune response inhibitors, but the data are still preliminary.”
“I would propose this data is very intriguing, but it was retrospectively generated, so I consider it hypothesis-generating,” said Sumanta Pal, MD, of City of Hope Medical Center in Duarte, Calif., and moderator of the press briefing. “One has to consider the fact that antibiotics are used under circumstances of medical necessity. I wouldn’t forgo treatment of any active infection … I would use as medically necessary.”
Beta-lactamases and fluoroquinolones comprised the majority of antibiotics in the study. The majority, 67 patients, received immune monotherapy with single-agent PD-1 or PD-L1 inhibitors. Another 10 patients received a combination of a PD-1 inhibitor and a CTLA-4 inhibitor, and 3 were treated with a PD-L1 inhibitor and bevacizumab.
“This is the first analysis evaluating impact of antibiotics on outcome of advanced renal carcinoma patients treated in the era of immune checkpoint blockade,” Dr. Derosa said. “We have a lot of work to do.” She and her colleagues plan to continue enrolling patients in the study. They also plan to evaluate whether alteration of the microbiome composition does play a role in diminishing the effectiveness of immunotherapy, and if so, which types of bacteria are the most likely culprits.
FROM THE GENITOURINARY CANCERS SYMPOSIUM
Key clinical point: The effectiveness of immune checkpoint inhibitors for patients with metastatic renal cell carcinoma may be hampered by antibiotic use.
Major finding: Patients treated with antibiotics had significantly shorter progression-free survival, 2.3 months versus 8.1 months (P less than.001).
Data source: Retrospective study of 80 patients treated with immune checkpoint inhibitors.
Disclosures: The study was supported by grants from the Philanthropia Foundation. Dr. Derosa had no relevant financial disclosures.
Circulating tumor DNA could guide therapy for advanced prostate cancer
ORLANDO – New research indicates that genetic changes over time in circulating cell-free tumor DNA of patients with advanced prostate cancer could help clinicians detect emerging treatment resistance and adjust treatment regimens accordingly. Also, specific genetic changes were associated with worse outcomes, suggesting a role in prognosis for these “liquid biopsies.”
In addition, the genetic changes detected in the 10-mL blood samples were similar to those seen in traditional tissue biopsies, indicating a noninvasive strategy could be a viable alternative in the future.
In contrast, circulating tumor DNA testing is noninvasive and not confounded by sampling bias of the biopsy, Dr. Sonpavde said during a press briefing prior to the 2017 genitourinary cancers symposium sponsored by the American Society of Clinical Oncology, ASTRO, and the Society of Urologic Oncology.
Dr. Sonpavde and his colleagues analyzed blood samples from 514 people with metastatic castration-resistant prostate cancer. They used a commercially available test to assess the cell-free, circulating tumor DNA (ctDNA) for 73 cancer-related, potentially actionable genes.
An overwhelming majority of patients, 94%, had at least one genetic change. “The most important takeaway is that ctDNA is frequently seen in patients with metastatic castration-resistant prostate cancer,” Dr. Sonpavde said. “So it looks rather promising for studying this tumor with ctDNA assays.”
“Circulating tumor DNA offers a simple and convenient way to assess an individual patient’s tumor DNA composition, and often, it can reveal new mutations clinicians like me can use to personalize therapy,” said Sumanta Pal, MD, of City of Hope Medical Center in Duarte, Calif. and moderator of the press briefing.
A likely target will be the androgen receptor (AR) gene, which was found in 22% of patients in the study. Other common recurrent somatic mutations occurred in TP53, APC, NF1, EGFR, CTNNB1, ARID1A, BRCA1, BRCA2, and PIK3CA genes, affecting from 36% to 5% of patients. The AR gene was also one of the most commonly amplified genes in the study, with an increase in copy numbers observed in 30% of patients. Increased cancer gene copies can spur an overabundance of proteins that drive cancer growth.
Alterations and outcomes
Investigators also performed a subanalysis of 163 patients for whom they had clinical values and outcome information. “What we found was something interesting,” Dr. Sonpavde said. “A higher number of overall ctDNA gene alterations and AR alterations appeared associated with poor clinical outcomes.”
For example, a higher number of any alterations of the genes on the panel was associated with a shorter time to failure (hazard ratio, 1.05; P = .026). In addition, AR gene changes were associated with a trend for shorter time to failure (HR, 1.42; P = .053) and survival (HR, 2.51), although the survival difference in this instance was not statistically significant (P = 0.09). The investigators also report that treatment-naive patients were less likely to develop AR gene changes, compared with previously treated patient (37% versus 56%; P = .028).
Changes over time could be prognostic
Of the group of patients with outcomes information, 63 underwent serial blood testing. “What we found in this subset is that the evolution of alterations in AR was the most frequent new alteration found,” again underlining its importance as a therapeutic target, Dr. Sonpavde said. Another important implication of emerging mutations is development of treatment resistance and a need to switch individual patients to a more effective treatment.
“New mutations in AR protein are important … because AR is the most common target of hormone therapies for prostate cancer,” Dr. Pal said. “This suggests that developing new agents that target this protein more effectively is certainly a good direction for future research.”
Guiding new treatment targets
An estimated 161,360 men in the United States will be diagnosed with prostate cancer in 2017 and close to 27,000 will die from the disease, according to American Cancer Society Facts & Figures 2017. Although no treatments are yet Food and Drug Administration–approved to treat prostate cancer based on specific genetic mutations, several therapies are in development. Results from the study could be used to identify novel molecular targets for future therapy, the authors said, provided a prospective, controlled trial confirms that treatment guidance based on the blood test in the study improves patient outcomes.
“In terms of next steps, it would be interesting to look at patients given therapy based on the alterations found, which would help us develop tailored and more efficient medicine,” Dr. Sonpavde said.
Dr. Sonpavde is a consultant/advisor for Bayer, Genetech, Sanofi, Merck, Novartis, Pfizer, Argos Therapeutics and Agensys; a member of the speakers’ bureau for Clinical Care Options/NCCN; receives honoraria from UpToDate; and receives institutional research funding from Onyx, Bayer, and Boehringer Ingelheim. Dr. Pal had no relevant financial disclosures.
ORLANDO – New research indicates that genetic changes over time in circulating cell-free tumor DNA of patients with advanced prostate cancer could help clinicians detect emerging treatment resistance and adjust treatment regimens accordingly. Also, specific genetic changes were associated with worse outcomes, suggesting a role in prognosis for these “liquid biopsies.”
In addition, the genetic changes detected in the 10-mL blood samples were similar to those seen in traditional tissue biopsies, indicating a noninvasive strategy could be a viable alternative in the future.
In contrast, circulating tumor DNA testing is noninvasive and not confounded by sampling bias of the biopsy, Dr. Sonpavde said during a press briefing prior to the 2017 genitourinary cancers symposium sponsored by the American Society of Clinical Oncology, ASTRO, and the Society of Urologic Oncology.
Dr. Sonpavde and his colleagues analyzed blood samples from 514 people with metastatic castration-resistant prostate cancer. They used a commercially available test to assess the cell-free, circulating tumor DNA (ctDNA) for 73 cancer-related, potentially actionable genes.
An overwhelming majority of patients, 94%, had at least one genetic change. “The most important takeaway is that ctDNA is frequently seen in patients with metastatic castration-resistant prostate cancer,” Dr. Sonpavde said. “So it looks rather promising for studying this tumor with ctDNA assays.”
“Circulating tumor DNA offers a simple and convenient way to assess an individual patient’s tumor DNA composition, and often, it can reveal new mutations clinicians like me can use to personalize therapy,” said Sumanta Pal, MD, of City of Hope Medical Center in Duarte, Calif. and moderator of the press briefing.
A likely target will be the androgen receptor (AR) gene, which was found in 22% of patients in the study. Other common recurrent somatic mutations occurred in TP53, APC, NF1, EGFR, CTNNB1, ARID1A, BRCA1, BRCA2, and PIK3CA genes, affecting from 36% to 5% of patients. The AR gene was also one of the most commonly amplified genes in the study, with an increase in copy numbers observed in 30% of patients. Increased cancer gene copies can spur an overabundance of proteins that drive cancer growth.
Alterations and outcomes
Investigators also performed a subanalysis of 163 patients for whom they had clinical values and outcome information. “What we found was something interesting,” Dr. Sonpavde said. “A higher number of overall ctDNA gene alterations and AR alterations appeared associated with poor clinical outcomes.”
For example, a higher number of any alterations of the genes on the panel was associated with a shorter time to failure (hazard ratio, 1.05; P = .026). In addition, AR gene changes were associated with a trend for shorter time to failure (HR, 1.42; P = .053) and survival (HR, 2.51), although the survival difference in this instance was not statistically significant (P = 0.09). The investigators also report that treatment-naive patients were less likely to develop AR gene changes, compared with previously treated patient (37% versus 56%; P = .028).
Changes over time could be prognostic
Of the group of patients with outcomes information, 63 underwent serial blood testing. “What we found in this subset is that the evolution of alterations in AR was the most frequent new alteration found,” again underlining its importance as a therapeutic target, Dr. Sonpavde said. Another important implication of emerging mutations is development of treatment resistance and a need to switch individual patients to a more effective treatment.
“New mutations in AR protein are important … because AR is the most common target of hormone therapies for prostate cancer,” Dr. Pal said. “This suggests that developing new agents that target this protein more effectively is certainly a good direction for future research.”
Guiding new treatment targets
An estimated 161,360 men in the United States will be diagnosed with prostate cancer in 2017 and close to 27,000 will die from the disease, according to American Cancer Society Facts & Figures 2017. Although no treatments are yet Food and Drug Administration–approved to treat prostate cancer based on specific genetic mutations, several therapies are in development. Results from the study could be used to identify novel molecular targets for future therapy, the authors said, provided a prospective, controlled trial confirms that treatment guidance based on the blood test in the study improves patient outcomes.
“In terms of next steps, it would be interesting to look at patients given therapy based on the alterations found, which would help us develop tailored and more efficient medicine,” Dr. Sonpavde said.
Dr. Sonpavde is a consultant/advisor for Bayer, Genetech, Sanofi, Merck, Novartis, Pfizer, Argos Therapeutics and Agensys; a member of the speakers’ bureau for Clinical Care Options/NCCN; receives honoraria from UpToDate; and receives institutional research funding from Onyx, Bayer, and Boehringer Ingelheim. Dr. Pal had no relevant financial disclosures.
ORLANDO – New research indicates that genetic changes over time in circulating cell-free tumor DNA of patients with advanced prostate cancer could help clinicians detect emerging treatment resistance and adjust treatment regimens accordingly. Also, specific genetic changes were associated with worse outcomes, suggesting a role in prognosis for these “liquid biopsies.”
In addition, the genetic changes detected in the 10-mL blood samples were similar to those seen in traditional tissue biopsies, indicating a noninvasive strategy could be a viable alternative in the future.
In contrast, circulating tumor DNA testing is noninvasive and not confounded by sampling bias of the biopsy, Dr. Sonpavde said during a press briefing prior to the 2017 genitourinary cancers symposium sponsored by the American Society of Clinical Oncology, ASTRO, and the Society of Urologic Oncology.
Dr. Sonpavde and his colleagues analyzed blood samples from 514 people with metastatic castration-resistant prostate cancer. They used a commercially available test to assess the cell-free, circulating tumor DNA (ctDNA) for 73 cancer-related, potentially actionable genes.
An overwhelming majority of patients, 94%, had at least one genetic change. “The most important takeaway is that ctDNA is frequently seen in patients with metastatic castration-resistant prostate cancer,” Dr. Sonpavde said. “So it looks rather promising for studying this tumor with ctDNA assays.”
“Circulating tumor DNA offers a simple and convenient way to assess an individual patient’s tumor DNA composition, and often, it can reveal new mutations clinicians like me can use to personalize therapy,” said Sumanta Pal, MD, of City of Hope Medical Center in Duarte, Calif. and moderator of the press briefing.
A likely target will be the androgen receptor (AR) gene, which was found in 22% of patients in the study. Other common recurrent somatic mutations occurred in TP53, APC, NF1, EGFR, CTNNB1, ARID1A, BRCA1, BRCA2, and PIK3CA genes, affecting from 36% to 5% of patients. The AR gene was also one of the most commonly amplified genes in the study, with an increase in copy numbers observed in 30% of patients. Increased cancer gene copies can spur an overabundance of proteins that drive cancer growth.
Alterations and outcomes
Investigators also performed a subanalysis of 163 patients for whom they had clinical values and outcome information. “What we found was something interesting,” Dr. Sonpavde said. “A higher number of overall ctDNA gene alterations and AR alterations appeared associated with poor clinical outcomes.”
For example, a higher number of any alterations of the genes on the panel was associated with a shorter time to failure (hazard ratio, 1.05; P = .026). In addition, AR gene changes were associated with a trend for shorter time to failure (HR, 1.42; P = .053) and survival (HR, 2.51), although the survival difference in this instance was not statistically significant (P = 0.09). The investigators also report that treatment-naive patients were less likely to develop AR gene changes, compared with previously treated patient (37% versus 56%; P = .028).
Changes over time could be prognostic
Of the group of patients with outcomes information, 63 underwent serial blood testing. “What we found in this subset is that the evolution of alterations in AR was the most frequent new alteration found,” again underlining its importance as a therapeutic target, Dr. Sonpavde said. Another important implication of emerging mutations is development of treatment resistance and a need to switch individual patients to a more effective treatment.
“New mutations in AR protein are important … because AR is the most common target of hormone therapies for prostate cancer,” Dr. Pal said. “This suggests that developing new agents that target this protein more effectively is certainly a good direction for future research.”
Guiding new treatment targets
An estimated 161,360 men in the United States will be diagnosed with prostate cancer in 2017 and close to 27,000 will die from the disease, according to American Cancer Society Facts & Figures 2017. Although no treatments are yet Food and Drug Administration–approved to treat prostate cancer based on specific genetic mutations, several therapies are in development. Results from the study could be used to identify novel molecular targets for future therapy, the authors said, provided a prospective, controlled trial confirms that treatment guidance based on the blood test in the study improves patient outcomes.
“In terms of next steps, it would be interesting to look at patients given therapy based on the alterations found, which would help us develop tailored and more efficient medicine,” Dr. Sonpavde said.
Dr. Sonpavde is a consultant/advisor for Bayer, Genetech, Sanofi, Merck, Novartis, Pfizer, Argos Therapeutics and Agensys; a member of the speakers’ bureau for Clinical Care Options/NCCN; receives honoraria from UpToDate; and receives institutional research funding from Onyx, Bayer, and Boehringer Ingelheim. Dr. Pal had no relevant financial disclosures.
FROM THE GENITOURINARY CANCERS SYMPOSIUM
Key clinical point: A majority of patients with metastatic castration-resistant prostate cancer have detectable tumor DNA in their blood.
Major finding: 94% of 514 patients had one or more cancer-associated genetic alterations in their blood samples.
Data source: Retrospective study of 514 patients diagnosed with metastatic castration-resistant prostate cancer.
Disclosures: Dr. Sonpavde is a consultant/advisor for Bayer, Genetech, Sanofi, Merck, Novartis, Pfizer, Argos Therapeutics and Agensys; a member of the speakers’ bureau for Clinical Care Options/NCCN; receives honoraria from UpToDate; and receives institutional research funding from Onyx, Bayer, and Boehringer Ingelheim. Dr. Pal had no relevant financial disclosures.
GU Cancers Symposium to feature latest on immune checkpoint inhibitors, circulating tumor cells
Oncology Practice will be on site this coming week at the 2017 Genitourinary Cancers Symposium in Orlando with the latest on treatment of prostate, kidney, testicular, and urothelial cancers. Look for coverage of the best clinical presentations at the conference, hosted by the American Society of Clinical Oncology, ASTRO, and the Society of Urologic Oncology, including the following and more, beginning Thursday, Feb. 16:
- Outcomes of PD-1/PD-L1 responders who discontinued therapy for immune-related adverse events: Results of a cohort of patients with metastatic renal cell carcinoma. First author: Rana McKay, MD.
- Impact of antibiotics on outcome in patients with metastatic renal cell carcinoma treated with immune checkpoint inhibitors. First author: Lisa Derosa, MD.
- Circulating tumor (ct)-DNA alterations in metastatic castration-resistant prostate cancer (mCRPC): Association with outcomes and evolution with therapy. First author: Guru Sonpavde, MD.
- Evolution of circulating tumor DNA profile from first-line to second-line therapy in metastatic renal cell carcinoma.
- First author: Sumanta Pal, MD.
- Clinical significance of AR mRNA quantification from circulating tumor cells in men with metastatic castration-resistant prostate cancer treated with abiraterone (Abi) or enzalutamide (Enza). First author: John Silberstein, MD.
- Adjuvant androgen deprivation versus mitoxantrone plus prednisone plus ADT in high-risk prostate cancer patients following radical prostatectomy: A phase III intergroup trial (SWOG S9921) NCT00004124. First author: L. Glode, MD.
Oncology Practice will be on site this coming week at the 2017 Genitourinary Cancers Symposium in Orlando with the latest on treatment of prostate, kidney, testicular, and urothelial cancers. Look for coverage of the best clinical presentations at the conference, hosted by the American Society of Clinical Oncology, ASTRO, and the Society of Urologic Oncology, including the following and more, beginning Thursday, Feb. 16:
- Outcomes of PD-1/PD-L1 responders who discontinued therapy for immune-related adverse events: Results of a cohort of patients with metastatic renal cell carcinoma. First author: Rana McKay, MD.
- Impact of antibiotics on outcome in patients with metastatic renal cell carcinoma treated with immune checkpoint inhibitors. First author: Lisa Derosa, MD.
- Circulating tumor (ct)-DNA alterations in metastatic castration-resistant prostate cancer (mCRPC): Association with outcomes and evolution with therapy. First author: Guru Sonpavde, MD.
- Evolution of circulating tumor DNA profile from first-line to second-line therapy in metastatic renal cell carcinoma.
- First author: Sumanta Pal, MD.
- Clinical significance of AR mRNA quantification from circulating tumor cells in men with metastatic castration-resistant prostate cancer treated with abiraterone (Abi) or enzalutamide (Enza). First author: John Silberstein, MD.
- Adjuvant androgen deprivation versus mitoxantrone plus prednisone plus ADT in high-risk prostate cancer patients following radical prostatectomy: A phase III intergroup trial (SWOG S9921) NCT00004124. First author: L. Glode, MD.
Oncology Practice will be on site this coming week at the 2017 Genitourinary Cancers Symposium in Orlando with the latest on treatment of prostate, kidney, testicular, and urothelial cancers. Look for coverage of the best clinical presentations at the conference, hosted by the American Society of Clinical Oncology, ASTRO, and the Society of Urologic Oncology, including the following and more, beginning Thursday, Feb. 16:
- Outcomes of PD-1/PD-L1 responders who discontinued therapy for immune-related adverse events: Results of a cohort of patients with metastatic renal cell carcinoma. First author: Rana McKay, MD.
- Impact of antibiotics on outcome in patients with metastatic renal cell carcinoma treated with immune checkpoint inhibitors. First author: Lisa Derosa, MD.
- Circulating tumor (ct)-DNA alterations in metastatic castration-resistant prostate cancer (mCRPC): Association with outcomes and evolution with therapy. First author: Guru Sonpavde, MD.
- Evolution of circulating tumor DNA profile from first-line to second-line therapy in metastatic renal cell carcinoma.
- First author: Sumanta Pal, MD.
- Clinical significance of AR mRNA quantification from circulating tumor cells in men with metastatic castration-resistant prostate cancer treated with abiraterone (Abi) or enzalutamide (Enza). First author: John Silberstein, MD.
- Adjuvant androgen deprivation versus mitoxantrone plus prednisone plus ADT in high-risk prostate cancer patients following radical prostatectomy: A phase III intergroup trial (SWOG S9921) NCT00004124. First author: L. Glode, MD.
FROM THE GENITOURINARY CANCERS SYMPOSIUM
Coming Soon!
Watch for our onsite coverage of the 2017 Genitourinary Cancers Symposium, which will take place in Orlando, February 16-18.
Watch for our onsite coverage of the 2017 Genitourinary Cancers Symposium, which will take place in Orlando, February 16-18.
Watch for our onsite coverage of the 2017 Genitourinary Cancers Symposium, which will take place in Orlando, February 16-18.