TBD Meeting (3035-19)

CHICAGO – The Food and Drug Administration launched a new call center project to assist physicians seeking to help cancer patients access unapproved therapies.

MDedge/Neil Osterweil

Entitled “Project Facilitate,” the program aims to create a single point of contact with FDA oncology staff who can guide physicians through the process of submitting Expanded Access (EA) requests on behalf of individual patients.

“This is a pilot program to provide continuous support to health care professionals throughout the entire Expanded Access process,” Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Hematology and Oncology Products said during the unveiling of the project during a press briefing at the annual meeting of the American Society of Clinical Oncology.

Physicians utilizing Project Facilitate can expect a “concierge service” experience including advice on the information needed to complete requests, assistance completing forms, pharma/biotech contact information, independent review board resource options, and follow-up on patient outcomes.

The project will work in synergy with the Reagan-Udall EA Navigator website, an “online road map” for physicians and patients that was launched 2 years ago “to facilitate and coordinate and collaborate with the FDA to advance the science mission of FDA,” and which has been expanded in conjunction with Project Facilitate, Ellen V. Sigal, PhD, chair of the board of the Reagan-Udall Foundation for the FDA, said at the press briefing.

“EA Navigator delivers transparent, concise, and searchable information provided by companies about their Expanded Access policies,” Dr. Sigal said. “Today I’m pleased to announce that the Navigator now features Expanded Access opportunities listed in ClinicalTrials.gov for companies in the directory.

“For the first time, those who need quick access to drug availability and Expanded Access options will find it in one place without having to visit site by site by site, or sift through thousands of studies that don’t merit their needs,” she added, noting that EA Navigator will often be the first step for physicians before they engage with Project Facilitate.

Project Facilitate can be reached Monday-Friday, 9 a.m.-5 p.m. ET at 240-402-0004, or by email at OncProjectFacilitate@fda.hhs.gov.

CHICAGO – The Food and Drug Administration launched a new call center project to assist physicians seeking to help cancer patients access unapproved therapies.

MDedge/Neil Osterweil

Entitled “Project Facilitate,” the program aims to create a single point of contact with FDA oncology staff who can guide physicians through the process of submitting Expanded Access (EA) requests on behalf of individual patients.

“This is a pilot program to provide continuous support to health care professionals throughout the entire Expanded Access process,” Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Hematology and Oncology Products said during the unveiling of the project during a press briefing at the annual meeting of the American Society of Clinical Oncology.

Physicians utilizing Project Facilitate can expect a “concierge service” experience including advice on the information needed to complete requests, assistance completing forms, pharma/biotech contact information, independent review board resource options, and follow-up on patient outcomes.

The project will work in synergy with the Reagan-Udall EA Navigator website, an “online road map” for physicians and patients that was launched 2 years ago “to facilitate and coordinate and collaborate with the FDA to advance the science mission of FDA,” and which has been expanded in conjunction with Project Facilitate, Ellen V. Sigal, PhD, chair of the board of the Reagan-Udall Foundation for the FDA, said at the press briefing.

“EA Navigator delivers transparent, concise, and searchable information provided by companies about their Expanded Access policies,” Dr. Sigal said. “Today I’m pleased to announce that the Navigator now features Expanded Access opportunities listed in ClinicalTrials.gov for companies in the directory.

“For the first time, those who need quick access to drug availability and Expanded Access options will find it in one place without having to visit site by site by site, or sift through thousands of studies that don’t merit their needs,” she added, noting that EA Navigator will often be the first step for physicians before they engage with Project Facilitate.

Project Facilitate can be reached Monday-Friday, 9 a.m.-5 p.m. ET at 240-402-0004, or by email at OncProjectFacilitate@fda.hhs.gov.

CHICAGO – The Food and Drug Administration launched a new call center project to assist physicians seeking to help cancer patients access unapproved therapies.

MDedge/Neil Osterweil

Entitled “Project Facilitate,” the program aims to create a single point of contact with FDA oncology staff who can guide physicians through the process of submitting Expanded Access (EA) requests on behalf of individual patients.

“This is a pilot program to provide continuous support to health care professionals throughout the entire Expanded Access process,” Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Hematology and Oncology Products said during the unveiling of the project during a press briefing at the annual meeting of the American Society of Clinical Oncology.

Physicians utilizing Project Facilitate can expect a “concierge service” experience including advice on the information needed to complete requests, assistance completing forms, pharma/biotech contact information, independent review board resource options, and follow-up on patient outcomes.

The project will work in synergy with the Reagan-Udall EA Navigator website, an “online road map” for physicians and patients that was launched 2 years ago “to facilitate and coordinate and collaborate with the FDA to advance the science mission of FDA,” and which has been expanded in conjunction with Project Facilitate, Ellen V. Sigal, PhD, chair of the board of the Reagan-Udall Foundation for the FDA, said at the press briefing.

“EA Navigator delivers transparent, concise, and searchable information provided by companies about their Expanded Access policies,” Dr. Sigal said. “Today I’m pleased to announce that the Navigator now features Expanded Access opportunities listed in ClinicalTrials.gov for companies in the directory.

“For the first time, those who need quick access to drug availability and Expanded Access options will find it in one place without having to visit site by site by site, or sift through thousands of studies that don’t merit their needs,” she added, noting that EA Navigator will often be the first step for physicians before they engage with Project Facilitate.

Project Facilitate can be reached Monday-Friday, 9 a.m.-5 p.m. ET at 240-402-0004, or by email at OncProjectFacilitate@fda.hhs.gov.

CHICAGO – Patients with advanced urothelial cancer that has progressed following platinum-based chemotherapy and immunotherapy with checkpoint inhibitors have a poor prognosis and few effective therapeutic options.

But in a phase 2 trial in 125 patients with locally advanced or metastatic urothelial cancer, the investigational agent enfortumab vedotin was associated with a 44% objective response rate, including a 12% complete response rate and 32% partial response rate. The responses were observed across all subgroups, irrespective of response to prior immunotherapy or the presence of liver metastases, reported Daniel Petrylak, MD, a professor of medical oncology and urology at Yale Cancer Center in New Haven, Connecticut.

In a video interview at the annual meeting of the American Society of Clinical Oncology, Dr. Petrylak described how the agent is directed toward a novel target, Nectin-4, a protein expressed in about 97% of urothelial cancers and in other solid tumor types.

The study is sponsored by Seattle Genetics and Astellas Pharma. Dr. Petrylak disclosed a consulting or advisory role with Astellas and others, funding from Seattle Genetics, and financial relationships with multiple other companies.
 

CHICAGO – Patients with advanced urothelial cancer that has progressed following platinum-based chemotherapy and immunotherapy with checkpoint inhibitors have a poor prognosis and few effective therapeutic options.

But in a phase 2 trial in 125 patients with locally advanced or metastatic urothelial cancer, the investigational agent enfortumab vedotin was associated with a 44% objective response rate, including a 12% complete response rate and 32% partial response rate. The responses were observed across all subgroups, irrespective of response to prior immunotherapy or the presence of liver metastases, reported Daniel Petrylak, MD, a professor of medical oncology and urology at Yale Cancer Center in New Haven, Connecticut.

In a video interview at the annual meeting of the American Society of Clinical Oncology, Dr. Petrylak described how the agent is directed toward a novel target, Nectin-4, a protein expressed in about 97% of urothelial cancers and in other solid tumor types.

The study is sponsored by Seattle Genetics and Astellas Pharma. Dr. Petrylak disclosed a consulting or advisory role with Astellas and others, funding from Seattle Genetics, and financial relationships with multiple other companies.
 

CHICAGO – Patients with advanced urothelial cancer that has progressed following platinum-based chemotherapy and immunotherapy with checkpoint inhibitors have a poor prognosis and few effective therapeutic options.

But in a phase 2 trial in 125 patients with locally advanced or metastatic urothelial cancer, the investigational agent enfortumab vedotin was associated with a 44% objective response rate, including a 12% complete response rate and 32% partial response rate. The responses were observed across all subgroups, irrespective of response to prior immunotherapy or the presence of liver metastases, reported Daniel Petrylak, MD, a professor of medical oncology and urology at Yale Cancer Center in New Haven, Connecticut.

In a video interview at the annual meeting of the American Society of Clinical Oncology, Dr. Petrylak described how the agent is directed toward a novel target, Nectin-4, a protein expressed in about 97% of urothelial cancers and in other solid tumor types.

The study is sponsored by Seattle Genetics and Astellas Pharma. Dr. Petrylak disclosed a consulting or advisory role with Astellas and others, funding from Seattle Genetics, and financial relationships with multiple other companies.
 

CHICAGO – For colorectal cancer patients with liver metastases, laparoscopic surgery has short-term advantages over open surgery, including fewer complications and better quality of life as compared to open surgery. Now, there are data to show that long-term outcomes with the laparoscopic approach aren’t any worse with the laparoscopic approach.

In a video interview at the annual meeting of the American Society of Clinical Oncology, Åsmund Avdem Fretland, MD, discusses results of the 280-patient randomized OSLO-COMET study, including 5-year survival of 56% for the laparoscopic approach, and similarly, 57% for the open procedure.

Based on lower morbidity, and now similar life expectancy, more centers should be doing laparoscopic procedures for liver metastases, said Dr. Fretland, a surgeon in the department of HPB surgery at Oslo University Hospital.

For now, however, open surgery appears to be the dominant approach. According to a recent survey, just 22% of U.S. patients with colorectal liver metastases have laparoscopic surgery.

More data could help. Dr. Fretland said in the interview that more randomized trials are underway aimed at evaluating the long-term outcomes of laparoscopic versus open procedures.

Dr. Fretland reported honoraria from Olympus Medical Systems.

CHICAGO – For colorectal cancer patients with liver metastases, laparoscopic surgery has short-term advantages over open surgery, including fewer complications and better quality of life as compared to open surgery. Now, there are data to show that long-term outcomes with the laparoscopic approach aren’t any worse with the laparoscopic approach.

In a video interview at the annual meeting of the American Society of Clinical Oncology, Åsmund Avdem Fretland, MD, discusses results of the 280-patient randomized OSLO-COMET study, including 5-year survival of 56% for the laparoscopic approach, and similarly, 57% for the open procedure.

Based on lower morbidity, and now similar life expectancy, more centers should be doing laparoscopic procedures for liver metastases, said Dr. Fretland, a surgeon in the department of HPB surgery at Oslo University Hospital.

For now, however, open surgery appears to be the dominant approach. According to a recent survey, just 22% of U.S. patients with colorectal liver metastases have laparoscopic surgery.

More data could help. Dr. Fretland said in the interview that more randomized trials are underway aimed at evaluating the long-term outcomes of laparoscopic versus open procedures.

Dr. Fretland reported honoraria from Olympus Medical Systems.

CHICAGO – For colorectal cancer patients with liver metastases, laparoscopic surgery has short-term advantages over open surgery, including fewer complications and better quality of life as compared to open surgery. Now, there are data to show that long-term outcomes with the laparoscopic approach aren’t any worse with the laparoscopic approach.

In a video interview at the annual meeting of the American Society of Clinical Oncology, Åsmund Avdem Fretland, MD, discusses results of the 280-patient randomized OSLO-COMET study, including 5-year survival of 56% for the laparoscopic approach, and similarly, 57% for the open procedure.

Based on lower morbidity, and now similar life expectancy, more centers should be doing laparoscopic procedures for liver metastases, said Dr. Fretland, a surgeon in the department of HPB surgery at Oslo University Hospital.

For now, however, open surgery appears to be the dominant approach. According to a recent survey, just 22% of U.S. patients with colorectal liver metastases have laparoscopic surgery.

More data could help. Dr. Fretland said in the interview that more randomized trials are underway aimed at evaluating the long-term outcomes of laparoscopic versus open procedures.

Dr. Fretland reported honoraria from Olympus Medical Systems.

CHICAGO – Despite reducing risk of death by 22% versus placebo and improving progression-free survival, pembrolizumab did not meet prespecified criteria for significance of these efficacy end points in a phase 3 study in advanced hepatocellular carcinoma, an investigator reported.

The magnitude of benefit seen with pembrolizumab was nevertheless on par with results of the study that led to accelerated approval of the PD-1 inhibitor for hepatocellular carcinoma, Richard S. Finn, MD, of the University of California, Los Angeles, said at the annual meeting of the American Society of Clinical Oncology.

“These data support that the risk-benefit balance for pembrolizumab is favorable in the second line setting in hepatocellular carcinoma,” he said in an oral presentation on the phase 3 KEYNOTE-240 study.

Pembrolizumab did demonstrate “strong trends” in survival and other clinical characteristics in KEYNOTE-240, including response rate, duration of response, and a “very favorable” toxicity profile, said William P. Harris, MD, of the University of Washington and Fred Hutchinson Cancer Research Center, Seattle.

“I plan to continue to prescribe PD-1 inhibitors in the second-line setting, especially for those patients who show relative intolerance to tyrosine kinase inhibitors,” Dr. Harris said in a podium discussion of the results.

The Food and Drug Administration granted accelerated approval to the PD-1 inhibitor nivolumab in September 2017, and to pembrolizumab in November 2018, for treatment of patients with hepatocellular carcinoma who previously received sorafenib.

The accelerated approval of pembrolizumab was based on KEYNOTE-224, a single-arm, multicenter trial enrolling 104 patients with Child-Pugh Class A liver impairment who had disease progression on or after sorafenib, or were intolerant to sorafenib. Overall response rate in the study was 17%, with response durations ranging from 3.1 to 16.7 months.

The phase 3 KEYNOTE-240 study was designed to confirm the efficacy and safety of pembrolizumab in patients with hepatocellular carcinoma, Dr. Finn said. The study comprised 413 patients with Child Pugh class A, Barcelona Clinic Liver Cancer stage B/C disease who had previously received sorafenib. They were randomized 2:1 to pembrolizumab or placebo in addition to best supportive care for up to 35 cycles, or approximately 2 years of treatment.

Median overall survival was 13.9 months for the PD-1 inhibitor and 10.6 months for placebo, but the P value (.0238) did not meet a prespecified threshold of 0.0174 required to demonstrate statistical significance, according to Dr. Finn. Median progression-free survival was 3.0 months for pembrolizumab and 2.8 months for placebo, with a P value of .0186 that did not meet a prespecified value of .002.

The objective response rate was 18.3% and 4.4% for pembrolizumab and placebo, respectively (P = .00007), Dr. Finn reported. Duration of response was a median of 13.8 months for pembrolizumab, ranging from 1.5+ months to 23.6+ months, while for placebo, median duration of response was not yet reached, with a range of 2.8 to 20.4+ months, according to his report.

Rates of adverse events were similar between arms, according to Dr. Finn. While rates of grade 3-4 adverse events were higher in the pembrolizumab arm, those leading to treatment discontinuation were relatively low, he added.

About 10% of patients in the placebo arm subsequently received treatment with PD-1 or PD-L1 inhibitors, in an analysis that was prespecified in anticipation of new drugs that might be approved, according to Dr. Finn.

Ongoing now is KEYNOTE-394, another phase 3 study of pembrolizumab in previously treated, advanced hepatocellular carcinoma ongoing in the Asia Pacific region, Dr. Finn said.

Results of that phase 3 investigation could have important implications for the FDA’s subsequent analyses of pembrolizumab in this setting, according to Dr. Harris, the abstract discussant.

“I would recommend that they consider continued approval until they see results of the KEYNOTE-394 study, and take those results in sum,” he said in his presentation.

Dr. Finn reported disclosures related to AstraZeneca, Bayer, Bristol-Myers Squibb, Eisai, Exelixis, Genentech/Roche, Lilly, Merck, Novartis, and Pfizer.

SOURCE: Finn RS, et al. ASCO 2019. Abstract 4004.

CHICAGO – Despite reducing risk of death by 22% versus placebo and improving progression-free survival, pembrolizumab did not meet prespecified criteria for significance of these efficacy end points in a phase 3 study in advanced hepatocellular carcinoma, an investigator reported.

The magnitude of benefit seen with pembrolizumab was nevertheless on par with results of the study that led to accelerated approval of the PD-1 inhibitor for hepatocellular carcinoma, Richard S. Finn, MD, of the University of California, Los Angeles, said at the annual meeting of the American Society of Clinical Oncology.

“These data support that the risk-benefit balance for pembrolizumab is favorable in the second line setting in hepatocellular carcinoma,” he said in an oral presentation on the phase 3 KEYNOTE-240 study.

Pembrolizumab did demonstrate “strong trends” in survival and other clinical characteristics in KEYNOTE-240, including response rate, duration of response, and a “very favorable” toxicity profile, said William P. Harris, MD, of the University of Washington and Fred Hutchinson Cancer Research Center, Seattle.

“I plan to continue to prescribe PD-1 inhibitors in the second-line setting, especially for those patients who show relative intolerance to tyrosine kinase inhibitors,” Dr. Harris said in a podium discussion of the results.

The Food and Drug Administration granted accelerated approval to the PD-1 inhibitor nivolumab in September 2017, and to pembrolizumab in November 2018, for treatment of patients with hepatocellular carcinoma who previously received sorafenib.

The accelerated approval of pembrolizumab was based on KEYNOTE-224, a single-arm, multicenter trial enrolling 104 patients with Child-Pugh Class A liver impairment who had disease progression on or after sorafenib, or were intolerant to sorafenib. Overall response rate in the study was 17%, with response durations ranging from 3.1 to 16.7 months.

The phase 3 KEYNOTE-240 study was designed to confirm the efficacy and safety of pembrolizumab in patients with hepatocellular carcinoma, Dr. Finn said. The study comprised 413 patients with Child Pugh class A, Barcelona Clinic Liver Cancer stage B/C disease who had previously received sorafenib. They were randomized 2:1 to pembrolizumab or placebo in addition to best supportive care for up to 35 cycles, or approximately 2 years of treatment.

Median overall survival was 13.9 months for the PD-1 inhibitor and 10.6 months for placebo, but the P value (.0238) did not meet a prespecified threshold of 0.0174 required to demonstrate statistical significance, according to Dr. Finn. Median progression-free survival was 3.0 months for pembrolizumab and 2.8 months for placebo, with a P value of .0186 that did not meet a prespecified value of .002.

The objective response rate was 18.3% and 4.4% for pembrolizumab and placebo, respectively (P = .00007), Dr. Finn reported. Duration of response was a median of 13.8 months for pembrolizumab, ranging from 1.5+ months to 23.6+ months, while for placebo, median duration of response was not yet reached, with a range of 2.8 to 20.4+ months, according to his report.

Rates of adverse events were similar between arms, according to Dr. Finn. While rates of grade 3-4 adverse events were higher in the pembrolizumab arm, those leading to treatment discontinuation were relatively low, he added.

About 10% of patients in the placebo arm subsequently received treatment with PD-1 or PD-L1 inhibitors, in an analysis that was prespecified in anticipation of new drugs that might be approved, according to Dr. Finn.

Ongoing now is KEYNOTE-394, another phase 3 study of pembrolizumab in previously treated, advanced hepatocellular carcinoma ongoing in the Asia Pacific region, Dr. Finn said.

Results of that phase 3 investigation could have important implications for the FDA’s subsequent analyses of pembrolizumab in this setting, according to Dr. Harris, the abstract discussant.

“I would recommend that they consider continued approval until they see results of the KEYNOTE-394 study, and take those results in sum,” he said in his presentation.

Dr. Finn reported disclosures related to AstraZeneca, Bayer, Bristol-Myers Squibb, Eisai, Exelixis, Genentech/Roche, Lilly, Merck, Novartis, and Pfizer.

SOURCE: Finn RS, et al. ASCO 2019. Abstract 4004.

CHICAGO – Despite reducing risk of death by 22% versus placebo and improving progression-free survival, pembrolizumab did not meet prespecified criteria for significance of these efficacy end points in a phase 3 study in advanced hepatocellular carcinoma, an investigator reported.

The magnitude of benefit seen with pembrolizumab was nevertheless on par with results of the study that led to accelerated approval of the PD-1 inhibitor for hepatocellular carcinoma, Richard S. Finn, MD, of the University of California, Los Angeles, said at the annual meeting of the American Society of Clinical Oncology.

“These data support that the risk-benefit balance for pembrolizumab is favorable in the second line setting in hepatocellular carcinoma,” he said in an oral presentation on the phase 3 KEYNOTE-240 study.

Pembrolizumab did demonstrate “strong trends” in survival and other clinical characteristics in KEYNOTE-240, including response rate, duration of response, and a “very favorable” toxicity profile, said William P. Harris, MD, of the University of Washington and Fred Hutchinson Cancer Research Center, Seattle.

“I plan to continue to prescribe PD-1 inhibitors in the second-line setting, especially for those patients who show relative intolerance to tyrosine kinase inhibitors,” Dr. Harris said in a podium discussion of the results.

The Food and Drug Administration granted accelerated approval to the PD-1 inhibitor nivolumab in September 2017, and to pembrolizumab in November 2018, for treatment of patients with hepatocellular carcinoma who previously received sorafenib.

The accelerated approval of pembrolizumab was based on KEYNOTE-224, a single-arm, multicenter trial enrolling 104 patients with Child-Pugh Class A liver impairment who had disease progression on or after sorafenib, or were intolerant to sorafenib. Overall response rate in the study was 17%, with response durations ranging from 3.1 to 16.7 months.

The phase 3 KEYNOTE-240 study was designed to confirm the efficacy and safety of pembrolizumab in patients with hepatocellular carcinoma, Dr. Finn said. The study comprised 413 patients with Child Pugh class A, Barcelona Clinic Liver Cancer stage B/C disease who had previously received sorafenib. They were randomized 2:1 to pembrolizumab or placebo in addition to best supportive care for up to 35 cycles, or approximately 2 years of treatment.

Median overall survival was 13.9 months for the PD-1 inhibitor and 10.6 months for placebo, but the P value (.0238) did not meet a prespecified threshold of 0.0174 required to demonstrate statistical significance, according to Dr. Finn. Median progression-free survival was 3.0 months for pembrolizumab and 2.8 months for placebo, with a P value of .0186 that did not meet a prespecified value of .002.

The objective response rate was 18.3% and 4.4% for pembrolizumab and placebo, respectively (P = .00007), Dr. Finn reported. Duration of response was a median of 13.8 months for pembrolizumab, ranging from 1.5+ months to 23.6+ months, while for placebo, median duration of response was not yet reached, with a range of 2.8 to 20.4+ months, according to his report.

Rates of adverse events were similar between arms, according to Dr. Finn. While rates of grade 3-4 adverse events were higher in the pembrolizumab arm, those leading to treatment discontinuation were relatively low, he added.

About 10% of patients in the placebo arm subsequently received treatment with PD-1 or PD-L1 inhibitors, in an analysis that was prespecified in anticipation of new drugs that might be approved, according to Dr. Finn.

Ongoing now is KEYNOTE-394, another phase 3 study of pembrolizumab in previously treated, advanced hepatocellular carcinoma ongoing in the Asia Pacific region, Dr. Finn said.

Results of that phase 3 investigation could have important implications for the FDA’s subsequent analyses of pembrolizumab in this setting, according to Dr. Harris, the abstract discussant.

“I would recommend that they consider continued approval until they see results of the KEYNOTE-394 study, and take those results in sum,” he said in his presentation.

Dr. Finn reported disclosures related to AstraZeneca, Bayer, Bristol-Myers Squibb, Eisai, Exelixis, Genentech/Roche, Lilly, Merck, Novartis, and Pfizer.

SOURCE: Finn RS, et al. ASCO 2019. Abstract 4004.

CHICAGO – In patients with high-risk stage II colon cancer, capecitabine plus oxaliplatin (CAPOX) given for 3 months may have efficacy as good as that of 6 months, with considerably less toxicity, as suggested by results of a new analysis by the IDEA (International Duration Evaluation of Adjuvant Chemotherapy) Collaboration.

By contrast, 6 months of fluorouracil, leucovorin, and oxaliplatin (FOLFOX) had better efficacy than that of 3 months of FOLFOX, albeit with significantly more toxicity than the shorter duration of treatment, according to IDEA investigator Timothy Iveson, MD, FRCP, of University Hospital Southampton (England) NHS Foundation Trust.

“As oncologists, we have patients in front of us, and we have the ability to choose which chemotherapy regimen we would choose,” Dr. Iveson said in a presentation at the annual meeting of the American Society of Clinical Oncology, “and we now have good data on both the efficacy and also toxicity of the regimens according to duration of treatment, and therefore, that should really allow us to recommend both the chemotherapy regimen and duration of treatment to our patients.”

The findings echo those of the previous study by the collaborative group, presented at ASCO in 2017 and subsequently published in the New England Journal of Medicine, focused on patients with stage III colon cancer. The overall analysis was negative, in that they could not confirm the noninferiority of 3 versus 6 months of adjuvant FOLFOX or CAPOX in the overall population; however, further analysis showed that, specifically for CAPOX, 3 months of treatment delivered the same efficacy as 6 months, especially in the lower-risk subgroup.

Treatment of stage III colon cancer got “more complicated” as a result of that study, said David P. Ryan, MD, of Harvard Medical School, Boston.

That’s in part because the National Comprehensive Cancer Network (NCCN) colon cancer guidelines subsequently divided stage III disease into low and high risk, with different recommendations for each, he said in an oral presentation at the ASCO meeting.

Specifically, the NCCN’s preferred regimens for low-risk stage III disease (T1-3, N1) are now 3 months of CAPOX or 3-6 months of FOLFOX, while for high-risk stage III disease (T4, N1-2; T any, N2), the preferred regimens are 3-6 months of CAPOX or 6 months of FOLFOX.

“The reason for this study is the toxicity of oxaliplatin, particularly neuropathy,” Dr. Ryan said in his remarks from the podium. “It can be substantial and life altering.” The incidence of grade 2 or greater neuropathy was cut from about 45% to 15% by going from 6 to 3 months of treatment, though reporting of the rate of chronic neuropathy would be informative to better qualify these results, he said.

The more recent prospective, preplanned, pooled analysis from the IDEA group focused on the four phase 3 IDEA studies (SCOT, TOSCA, ACHIEVE-2, and HORG), out of six total studies, that enrolled high-risk stage II patients. Their primary analysis included 3,273 patients, of whom 2,019 received CAPOX and 1,254 received FOLFOX.

Rates of grade 2 or greater neuropathy were 36% for 6 months of treatment, but just 13% for 3 months of treatment. However, in the overall analysis, IDEA investigators could not demonstrate the noninferiority of 3 versus 6 months of treatment in terms of efficacy—similar to what was reported in the previously reported analysis of stage III patients.

Results for CAPOX, however, did demonstrate noninferiority, according to Dr. Iveson, with a 5-year disease-free survival (DFS) of 81.7% for 3 months of treatment versus 82.0% for 6 months, an absolute difference of 0.3%, he said in his presentation. By contrast, the 5-year DFS for FOLFOX was 79.2% for 3 months of treatment versus 86.5%, an absolute 7.3% difference in favor of longer treatment duration.

“Therefore, the data strongly suggest noninferiority of 3 months’ CAPOX treatment compared to 6 months, but equally, it suggests inferiority of 3 months FOLFOX compared to 6 months,” Dr. Iveson said.

Whether these findings also change practice remains to be seen.

Dr. Ryan, discussant for the study, agreed that 3 months of CAPOX, but not FOLFOX, is likely sufficient for patients with high-risk stage II disease, with one caveat: “Remember, it is not proven as the primary endpoint,” he told attendees at ASCO.

He said a new era of adjuvant studies is needed to address individual subsets of colon cancer in the adjuvant setting, particularly those defined by different biologies, such as BRAF-mutant, MSI-high, or HER2-amplified.

“I have little enthusiasm to return to the fundamental question posed by IDEA in a new prospective study, given that the magnitude of benefit or difference is so small,” he said.

Dr. Iveson reported disclosures related to Lilly, Servier, BMS, Celgene, Roche, and Bayer.

CHICAGO – In patients with high-risk stage II colon cancer, capecitabine plus oxaliplatin (CAPOX) given for 3 months may have efficacy as good as that of 6 months, with considerably less toxicity, as suggested by results of a new analysis by the IDEA (International Duration Evaluation of Adjuvant Chemotherapy) Collaboration.

By contrast, 6 months of fluorouracil, leucovorin, and oxaliplatin (FOLFOX) had better efficacy than that of 3 months of FOLFOX, albeit with significantly more toxicity than the shorter duration of treatment, according to IDEA investigator Timothy Iveson, MD, FRCP, of University Hospital Southampton (England) NHS Foundation Trust.

“As oncologists, we have patients in front of us, and we have the ability to choose which chemotherapy regimen we would choose,” Dr. Iveson said in a presentation at the annual meeting of the American Society of Clinical Oncology, “and we now have good data on both the efficacy and also toxicity of the regimens according to duration of treatment, and therefore, that should really allow us to recommend both the chemotherapy regimen and duration of treatment to our patients.”

The findings echo those of the previous study by the collaborative group, presented at ASCO in 2017 and subsequently published in the New England Journal of Medicine, focused on patients with stage III colon cancer. The overall analysis was negative, in that they could not confirm the noninferiority of 3 versus 6 months of adjuvant FOLFOX or CAPOX in the overall population; however, further analysis showed that, specifically for CAPOX, 3 months of treatment delivered the same efficacy as 6 months, especially in the lower-risk subgroup.

Treatment of stage III colon cancer got “more complicated” as a result of that study, said David P. Ryan, MD, of Harvard Medical School, Boston.

That’s in part because the National Comprehensive Cancer Network (NCCN) colon cancer guidelines subsequently divided stage III disease into low and high risk, with different recommendations for each, he said in an oral presentation at the ASCO meeting.

Specifically, the NCCN’s preferred regimens for low-risk stage III disease (T1-3, N1) are now 3 months of CAPOX or 3-6 months of FOLFOX, while for high-risk stage III disease (T4, N1-2; T any, N2), the preferred regimens are 3-6 months of CAPOX or 6 months of FOLFOX.

“The reason for this study is the toxicity of oxaliplatin, particularly neuropathy,” Dr. Ryan said in his remarks from the podium. “It can be substantial and life altering.” The incidence of grade 2 or greater neuropathy was cut from about 45% to 15% by going from 6 to 3 months of treatment, though reporting of the rate of chronic neuropathy would be informative to better qualify these results, he said.

The more recent prospective, preplanned, pooled analysis from the IDEA group focused on the four phase 3 IDEA studies (SCOT, TOSCA, ACHIEVE-2, and HORG), out of six total studies, that enrolled high-risk stage II patients. Their primary analysis included 3,273 patients, of whom 2,019 received CAPOX and 1,254 received FOLFOX.

Rates of grade 2 or greater neuropathy were 36% for 6 months of treatment, but just 13% for 3 months of treatment. However, in the overall analysis, IDEA investigators could not demonstrate the noninferiority of 3 versus 6 months of treatment in terms of efficacy—similar to what was reported in the previously reported analysis of stage III patients.

Results for CAPOX, however, did demonstrate noninferiority, according to Dr. Iveson, with a 5-year disease-free survival (DFS) of 81.7% for 3 months of treatment versus 82.0% for 6 months, an absolute difference of 0.3%, he said in his presentation. By contrast, the 5-year DFS for FOLFOX was 79.2% for 3 months of treatment versus 86.5%, an absolute 7.3% difference in favor of longer treatment duration.

“Therefore, the data strongly suggest noninferiority of 3 months’ CAPOX treatment compared to 6 months, but equally, it suggests inferiority of 3 months FOLFOX compared to 6 months,” Dr. Iveson said.

Whether these findings also change practice remains to be seen.

Dr. Ryan, discussant for the study, agreed that 3 months of CAPOX, but not FOLFOX, is likely sufficient for patients with high-risk stage II disease, with one caveat: “Remember, it is not proven as the primary endpoint,” he told attendees at ASCO.

He said a new era of adjuvant studies is needed to address individual subsets of colon cancer in the adjuvant setting, particularly those defined by different biologies, such as BRAF-mutant, MSI-high, or HER2-amplified.

“I have little enthusiasm to return to the fundamental question posed by IDEA in a new prospective study, given that the magnitude of benefit or difference is so small,” he said.

Dr. Iveson reported disclosures related to Lilly, Servier, BMS, Celgene, Roche, and Bayer.

CHICAGO – In patients with high-risk stage II colon cancer, capecitabine plus oxaliplatin (CAPOX) given for 3 months may have efficacy as good as that of 6 months, with considerably less toxicity, as suggested by results of a new analysis by the IDEA (International Duration Evaluation of Adjuvant Chemotherapy) Collaboration.

By contrast, 6 months of fluorouracil, leucovorin, and oxaliplatin (FOLFOX) had better efficacy than that of 3 months of FOLFOX, albeit with significantly more toxicity than the shorter duration of treatment, according to IDEA investigator Timothy Iveson, MD, FRCP, of University Hospital Southampton (England) NHS Foundation Trust.

“As oncologists, we have patients in front of us, and we have the ability to choose which chemotherapy regimen we would choose,” Dr. Iveson said in a presentation at the annual meeting of the American Society of Clinical Oncology, “and we now have good data on both the efficacy and also toxicity of the regimens according to duration of treatment, and therefore, that should really allow us to recommend both the chemotherapy regimen and duration of treatment to our patients.”

The findings echo those of the previous study by the collaborative group, presented at ASCO in 2017 and subsequently published in the New England Journal of Medicine, focused on patients with stage III colon cancer. The overall analysis was negative, in that they could not confirm the noninferiority of 3 versus 6 months of adjuvant FOLFOX or CAPOX in the overall population; however, further analysis showed that, specifically for CAPOX, 3 months of treatment delivered the same efficacy as 6 months, especially in the lower-risk subgroup.

Treatment of stage III colon cancer got “more complicated” as a result of that study, said David P. Ryan, MD, of Harvard Medical School, Boston.

That’s in part because the National Comprehensive Cancer Network (NCCN) colon cancer guidelines subsequently divided stage III disease into low and high risk, with different recommendations for each, he said in an oral presentation at the ASCO meeting.

Specifically, the NCCN’s preferred regimens for low-risk stage III disease (T1-3, N1) are now 3 months of CAPOX or 3-6 months of FOLFOX, while for high-risk stage III disease (T4, N1-2; T any, N2), the preferred regimens are 3-6 months of CAPOX or 6 months of FOLFOX.

“The reason for this study is the toxicity of oxaliplatin, particularly neuropathy,” Dr. Ryan said in his remarks from the podium. “It can be substantial and life altering.” The incidence of grade 2 or greater neuropathy was cut from about 45% to 15% by going from 6 to 3 months of treatment, though reporting of the rate of chronic neuropathy would be informative to better qualify these results, he said.

The more recent prospective, preplanned, pooled analysis from the IDEA group focused on the four phase 3 IDEA studies (SCOT, TOSCA, ACHIEVE-2, and HORG), out of six total studies, that enrolled high-risk stage II patients. Their primary analysis included 3,273 patients, of whom 2,019 received CAPOX and 1,254 received FOLFOX.

Rates of grade 2 or greater neuropathy were 36% for 6 months of treatment, but just 13% for 3 months of treatment. However, in the overall analysis, IDEA investigators could not demonstrate the noninferiority of 3 versus 6 months of treatment in terms of efficacy—similar to what was reported in the previously reported analysis of stage III patients.

Results for CAPOX, however, did demonstrate noninferiority, according to Dr. Iveson, with a 5-year disease-free survival (DFS) of 81.7% for 3 months of treatment versus 82.0% for 6 months, an absolute difference of 0.3%, he said in his presentation. By contrast, the 5-year DFS for FOLFOX was 79.2% for 3 months of treatment versus 86.5%, an absolute 7.3% difference in favor of longer treatment duration.

“Therefore, the data strongly suggest noninferiority of 3 months’ CAPOX treatment compared to 6 months, but equally, it suggests inferiority of 3 months FOLFOX compared to 6 months,” Dr. Iveson said.

Whether these findings also change practice remains to be seen.

Dr. Ryan, discussant for the study, agreed that 3 months of CAPOX, but not FOLFOX, is likely sufficient for patients with high-risk stage II disease, with one caveat: “Remember, it is not proven as the primary endpoint,” he told attendees at ASCO.

He said a new era of adjuvant studies is needed to address individual subsets of colon cancer in the adjuvant setting, particularly those defined by different biologies, such as BRAF-mutant, MSI-high, or HER2-amplified.

“I have little enthusiasm to return to the fundamental question posed by IDEA in a new prospective study, given that the magnitude of benefit or difference is so small,” he said.

Dr. Iveson reported disclosures related to Lilly, Servier, BMS, Celgene, Roche, and Bayer.

CHICAGO – Adding the oral androgen receptor inhibitor enzalutamide to standard first-line testosterone suppression delays progression and improves survival in men with metastatic hormone-sensitive prostate cancer (mHSPC), according to “practice-informing” interim results from the randomized phase 3 ENZAMET trial.

The survival rate at 3 years in 563 men with mHSPC who were enrolled in the international trial and who received early testosterone suppression and enzalutamide was 80%, compared with 72% among 562 men who received testosterone suppression and standard nonsteroidal antiandrogen therapy with or without docetaxel, study cochair Christopher Sweeney, MBBS, reported at the annual meeting of the American Society of Clinical Oncology (Abstract LBA2).

The findings of the Australian and New Zealand Urogenital and Prostate (ANZUP) Cancer Trials Group study (ANZUP 1304/ENZAMET) were published simultaneously in the New England Journal of Medicine.

“So ... we’re moving forward by going backwards in the disease setting where the disease is more sensitive and responds better to therapy,” Dr. Sweeney, of Dana-Farber Cancer Institute’s Lank Center for Genitourinary Oncology and professor of medicine at Harvard Medical School, Boston, explained in this video interview.

He also described the future directions for the research – in particular the need for longer follow-up to clarify the effects of docetaxel in this setting – and how the current findings will be reflected in his own management of patients with prostate cancer.

The findings have immediate implications for practice, ASCO expert Neeraj Agarwal, MD, professor of medicine and investigator at the Huntsman Cancer Institute, University of Utah, Salt Lake City, said during a press briefing at the meeting.

“In my view, using enzalutamide early on will allow our patients to avoid chemotherapy and steroids for many years, and thus, hopefully, improve their quality of life,” he said, noting that the findings are particularly exciting when considered in the context of the “equally impressive margin of benefit” seen with the similar drug apalutamide in the TITAN trial, which was presented separately during the ASCO meeting.

“One study is encouraging, but two large studies ... demonstrating similar findings, is even better,” he said. “This increases my confidence that targeting [the androgen receptor] is the optimal approach for newly diagnosed patients with advanced prostate cancer.”

Dr. Sweeney reported relationships (stock and other ownership interests, consulting or advisory roles, research funding to his institution, and/or patents/royalties/other intellectual property) with Leuchemix, Amgen, Astellas Pharma, AstraZeneca, Bayer, Genentech/Roche, Janssen Biotech, Pfizer, Sanofi, Dendreon, Sotio, and Exelixis. Dr. Agarwal reported consultancy or research for Pfizer, Novartis, Exelixis, Eisai, Genentech, Medivation, Clovis, Merck, Bayer, GlaxoSmithKline, AstraZeneca, EMD Serono, and Bristol-Myers Squibb.

CHICAGO – Adding the oral androgen receptor inhibitor enzalutamide to standard first-line testosterone suppression delays progression and improves survival in men with metastatic hormone-sensitive prostate cancer (mHSPC), according to “practice-informing” interim results from the randomized phase 3 ENZAMET trial.

The survival rate at 3 years in 563 men with mHSPC who were enrolled in the international trial and who received early testosterone suppression and enzalutamide was 80%, compared with 72% among 562 men who received testosterone suppression and standard nonsteroidal antiandrogen therapy with or without docetaxel, study cochair Christopher Sweeney, MBBS, reported at the annual meeting of the American Society of Clinical Oncology (Abstract LBA2).

The findings of the Australian and New Zealand Urogenital and Prostate (ANZUP) Cancer Trials Group study (ANZUP 1304/ENZAMET) were published simultaneously in the New England Journal of Medicine.

“So ... we’re moving forward by going backwards in the disease setting where the disease is more sensitive and responds better to therapy,” Dr. Sweeney, of Dana-Farber Cancer Institute’s Lank Center for Genitourinary Oncology and professor of medicine at Harvard Medical School, Boston, explained in this video interview.

He also described the future directions for the research – in particular the need for longer follow-up to clarify the effects of docetaxel in this setting – and how the current findings will be reflected in his own management of patients with prostate cancer.

The findings have immediate implications for practice, ASCO expert Neeraj Agarwal, MD, professor of medicine and investigator at the Huntsman Cancer Institute, University of Utah, Salt Lake City, said during a press briefing at the meeting.

“In my view, using enzalutamide early on will allow our patients to avoid chemotherapy and steroids for many years, and thus, hopefully, improve their quality of life,” he said, noting that the findings are particularly exciting when considered in the context of the “equally impressive margin of benefit” seen with the similar drug apalutamide in the TITAN trial, which was presented separately during the ASCO meeting.

“One study is encouraging, but two large studies ... demonstrating similar findings, is even better,” he said. “This increases my confidence that targeting [the androgen receptor] is the optimal approach for newly diagnosed patients with advanced prostate cancer.”

Dr. Sweeney reported relationships (stock and other ownership interests, consulting or advisory roles, research funding to his institution, and/or patents/royalties/other intellectual property) with Leuchemix, Amgen, Astellas Pharma, AstraZeneca, Bayer, Genentech/Roche, Janssen Biotech, Pfizer, Sanofi, Dendreon, Sotio, and Exelixis. Dr. Agarwal reported consultancy or research for Pfizer, Novartis, Exelixis, Eisai, Genentech, Medivation, Clovis, Merck, Bayer, GlaxoSmithKline, AstraZeneca, EMD Serono, and Bristol-Myers Squibb.

CHICAGO – Adding the oral androgen receptor inhibitor enzalutamide to standard first-line testosterone suppression delays progression and improves survival in men with metastatic hormone-sensitive prostate cancer (mHSPC), according to “practice-informing” interim results from the randomized phase 3 ENZAMET trial.

The survival rate at 3 years in 563 men with mHSPC who were enrolled in the international trial and who received early testosterone suppression and enzalutamide was 80%, compared with 72% among 562 men who received testosterone suppression and standard nonsteroidal antiandrogen therapy with or without docetaxel, study cochair Christopher Sweeney, MBBS, reported at the annual meeting of the American Society of Clinical Oncology (Abstract LBA2).

The findings of the Australian and New Zealand Urogenital and Prostate (ANZUP) Cancer Trials Group study (ANZUP 1304/ENZAMET) were published simultaneously in the New England Journal of Medicine.

“So ... we’re moving forward by going backwards in the disease setting where the disease is more sensitive and responds better to therapy,” Dr. Sweeney, of Dana-Farber Cancer Institute’s Lank Center for Genitourinary Oncology and professor of medicine at Harvard Medical School, Boston, explained in this video interview.

He also described the future directions for the research – in particular the need for longer follow-up to clarify the effects of docetaxel in this setting – and how the current findings will be reflected in his own management of patients with prostate cancer.

The findings have immediate implications for practice, ASCO expert Neeraj Agarwal, MD, professor of medicine and investigator at the Huntsman Cancer Institute, University of Utah, Salt Lake City, said during a press briefing at the meeting.

“In my view, using enzalutamide early on will allow our patients to avoid chemotherapy and steroids for many years, and thus, hopefully, improve their quality of life,” he said, noting that the findings are particularly exciting when considered in the context of the “equally impressive margin of benefit” seen with the similar drug apalutamide in the TITAN trial, which was presented separately during the ASCO meeting.

“One study is encouraging, but two large studies ... demonstrating similar findings, is even better,” he said. “This increases my confidence that targeting [the androgen receptor] is the optimal approach for newly diagnosed patients with advanced prostate cancer.”

Dr. Sweeney reported relationships (stock and other ownership interests, consulting or advisory roles, research funding to his institution, and/or patents/royalties/other intellectual property) with Leuchemix, Amgen, Astellas Pharma, AstraZeneca, Bayer, Genentech/Roche, Janssen Biotech, Pfizer, Sanofi, Dendreon, Sotio, and Exelixis. Dr. Agarwal reported consultancy or research for Pfizer, Novartis, Exelixis, Eisai, Genentech, Medivation, Clovis, Merck, Bayer, GlaxoSmithKline, AstraZeneca, EMD Serono, and Bristol-Myers Squibb.

CHICAGO – For decades investigators have documented racial disparities in access to cancer care and in clinical outcomes, with socioeconomic factors suspected – but not conclusively proven – to play a role

Now a new study based on electronic health record (EHR) data shows that after Medicaid expansion under the Affordable Care Act (ACA), racial differences in timely cancer treatment effectively disappeared. Before Medicaid expansion, African Americans were 4.8% less likely than whites to receive timely cancer treatment, defined as treatment starting within 30 days of diagnosis of an advanced or metastatic solid tumor. After Medicaid expansion, however, the difference between the racial groups had dwindled to just 0.8% and was no longer statistically significant.

The findings suggest that the expanded availability of health insurance has had a salutary effect on cancer care.

In this video interview, co-authors Amy J. Davidoff, PhD, MS, from the Yale Cancer Center in New Haven Connecticut, and Blythe J.S. Adamson, PhD, from Flatiron Health in New York, New York, discuss the study findings and the possible implications for health care policy in the United States.

The study was funded by Flatiron Health. Dr. Adamson is an employee of the company. Dr. Davidoff disclosed consulting or advisory roles with and honoraria from several pharmaceutical companies.

CHICAGO – For decades investigators have documented racial disparities in access to cancer care and in clinical outcomes, with socioeconomic factors suspected – but not conclusively proven – to play a role

Now a new study based on electronic health record (EHR) data shows that after Medicaid expansion under the Affordable Care Act (ACA), racial differences in timely cancer treatment effectively disappeared. Before Medicaid expansion, African Americans were 4.8% less likely than whites to receive timely cancer treatment, defined as treatment starting within 30 days of diagnosis of an advanced or metastatic solid tumor. After Medicaid expansion, however, the difference between the racial groups had dwindled to just 0.8% and was no longer statistically significant.

The findings suggest that the expanded availability of health insurance has had a salutary effect on cancer care.

In this video interview, co-authors Amy J. Davidoff, PhD, MS, from the Yale Cancer Center in New Haven Connecticut, and Blythe J.S. Adamson, PhD, from Flatiron Health in New York, New York, discuss the study findings and the possible implications for health care policy in the United States.

The study was funded by Flatiron Health. Dr. Adamson is an employee of the company. Dr. Davidoff disclosed consulting or advisory roles with and honoraria from several pharmaceutical companies.

CHICAGO – For decades investigators have documented racial disparities in access to cancer care and in clinical outcomes, with socioeconomic factors suspected – but not conclusively proven – to play a role

Now a new study based on electronic health record (EHR) data shows that after Medicaid expansion under the Affordable Care Act (ACA), racial differences in timely cancer treatment effectively disappeared. Before Medicaid expansion, African Americans were 4.8% less likely than whites to receive timely cancer treatment, defined as treatment starting within 30 days of diagnosis of an advanced or metastatic solid tumor. After Medicaid expansion, however, the difference between the racial groups had dwindled to just 0.8% and was no longer statistically significant.

The findings suggest that the expanded availability of health insurance has had a salutary effect on cancer care.

In this video interview, co-authors Amy J. Davidoff, PhD, MS, from the Yale Cancer Center in New Haven Connecticut, and Blythe J.S. Adamson, PhD, from Flatiron Health in New York, New York, discuss the study findings and the possible implications for health care policy in the United States.

The study was funded by Flatiron Health. Dr. Adamson is an employee of the company. Dr. Davidoff disclosed consulting or advisory roles with and honoraria from several pharmaceutical companies.

CHICAGO – In 2014, the average time from diagnosis to treatment initiation for new cancer patients at the Cleveland Clinic was 29-41 days, depending on whether the patient was diagnosed internally or externally. That figure was not acceptable, said Brian J. Bolwell, MD, chairman of the Cleveland Clinic’s Taussig Cancer Institute.

Since then, the time-to-treat metric has improved dramatically, dropping 33%. Today, time to treat for new cancer patients is 25-31 days, depending on the site of diagnosis.

To get there, leaders at the cancer center examined the causes of delay within each of their disease programs. The analysis revealed that less than 20% of the time it was patient preferences that slowed down the initiation of treatment, but that more than 80% of the time the delay was on the part of their institution.

Dr. Bolwell said this led them to start tracking every newly diagnosed patient who came through the cancer center to ensure they didn’t fall through the cracks, and that they were treated as rapidly as possible.

But figuring out how to get patients to treatment quicker depended on the type of cancer they had, since each type of cancer had different challenges and different points of entry to the health care system.

“So for breast cancer, it turns out a lot of the challenges might be coordination of surgery because sometimes a general surgeon has to work with a reconstructive-plastic surgeon and coordinating the surgical schedules might drastically lengthen time to treat,” he said during an interview at the annual meeting of the American Society of Clinical Oncology.

They helped address that problem by scheduling breast cancer patients for surgery by the next available operating room slot, rather than doing the scheduling by surgeon.

There are additional barriers to achieving a rapid time to treat standard, including prior authorization, Dr. Bolwell said. But they are continuing to chip away at the metric, working within each cancer type to lower the obstacles to treatment. “I don’t think we’ll ever be satisfied with where we are,” Dr. Bolwell said.

Dr. Bolwell reported having no relevant financial disclosures.

mschneider@mdedge.com

CHICAGO – In 2014, the average time from diagnosis to treatment initiation for new cancer patients at the Cleveland Clinic was 29-41 days, depending on whether the patient was diagnosed internally or externally. That figure was not acceptable, said Brian J. Bolwell, MD, chairman of the Cleveland Clinic’s Taussig Cancer Institute.

Since then, the time-to-treat metric has improved dramatically, dropping 33%. Today, time to treat for new cancer patients is 25-31 days, depending on the site of diagnosis.

To get there, leaders at the cancer center examined the causes of delay within each of their disease programs. The analysis revealed that less than 20% of the time it was patient preferences that slowed down the initiation of treatment, but that more than 80% of the time the delay was on the part of their institution.

Dr. Bolwell said this led them to start tracking every newly diagnosed patient who came through the cancer center to ensure they didn’t fall through the cracks, and that they were treated as rapidly as possible.

But figuring out how to get patients to treatment quicker depended on the type of cancer they had, since each type of cancer had different challenges and different points of entry to the health care system.

“So for breast cancer, it turns out a lot of the challenges might be coordination of surgery because sometimes a general surgeon has to work with a reconstructive-plastic surgeon and coordinating the surgical schedules might drastically lengthen time to treat,” he said during an interview at the annual meeting of the American Society of Clinical Oncology.

They helped address that problem by scheduling breast cancer patients for surgery by the next available operating room slot, rather than doing the scheduling by surgeon.

There are additional barriers to achieving a rapid time to treat standard, including prior authorization, Dr. Bolwell said. But they are continuing to chip away at the metric, working within each cancer type to lower the obstacles to treatment. “I don’t think we’ll ever be satisfied with where we are,” Dr. Bolwell said.

Dr. Bolwell reported having no relevant financial disclosures.

mschneider@mdedge.com

CHICAGO – In 2014, the average time from diagnosis to treatment initiation for new cancer patients at the Cleveland Clinic was 29-41 days, depending on whether the patient was diagnosed internally or externally. That figure was not acceptable, said Brian J. Bolwell, MD, chairman of the Cleveland Clinic’s Taussig Cancer Institute.

Since then, the time-to-treat metric has improved dramatically, dropping 33%. Today, time to treat for new cancer patients is 25-31 days, depending on the site of diagnosis.

To get there, leaders at the cancer center examined the causes of delay within each of their disease programs. The analysis revealed that less than 20% of the time it was patient preferences that slowed down the initiation of treatment, but that more than 80% of the time the delay was on the part of their institution.

Dr. Bolwell said this led them to start tracking every newly diagnosed patient who came through the cancer center to ensure they didn’t fall through the cracks, and that they were treated as rapidly as possible.

But figuring out how to get patients to treatment quicker depended on the type of cancer they had, since each type of cancer had different challenges and different points of entry to the health care system.

“So for breast cancer, it turns out a lot of the challenges might be coordination of surgery because sometimes a general surgeon has to work with a reconstructive-plastic surgeon and coordinating the surgical schedules might drastically lengthen time to treat,” he said during an interview at the annual meeting of the American Society of Clinical Oncology.

They helped address that problem by scheduling breast cancer patients for surgery by the next available operating room slot, rather than doing the scheduling by surgeon.

There are additional barriers to achieving a rapid time to treat standard, including prior authorization, Dr. Bolwell said. But they are continuing to chip away at the metric, working within each cancer type to lower the obstacles to treatment. “I don’t think we’ll ever be satisfied with where we are,” Dr. Bolwell said.

Dr. Bolwell reported having no relevant financial disclosures.

mschneider@mdedge.com

CHICAGO – In patients with metastatic pancreatic cancer and a germline BRCA mutation, maintenance treatment with olaparib resulted in significant and clinically meaningful improvements in progression-free survival in a phase 3 trial, an investigator reported.

For patients who completed chemotherapy and went on to receive the PARP inhibitor, median progression-free survival was 7.4 months, versus just 3.8 months for placebo-treated patients in the phase 3 POLO study, said Hedy L. Kindler, MD, professor of medicine with University of Chicago Medicine.

“A strategic approach of first-line platinum based chemo followed by maintenance olaparib treatment should become a new standard of care for patients with metastatic pancreatic cancer who have a germ line BRCA mutation,” Dr. Kindler said here in a press conference at the annual meeting of the American Society of Clinical Oncology.

This phase 3 study is the first to show that treatment of metastatic pancreatic cancer can be tailored based on a biomarker, highlights the importance of germline BRCA mutation testing, according to ASCO expert Suzanne Cole, MD.

“I think this is practice-changing for people who have BRCA mutations,” Dr. Cole said in the press conference. “I can’t wait to go back to clinic on Tuesday and look for it in my own patients.”

Four to seven percent of patients with pancreatic cancer harbor a germline BRCA1 or BRCA2 mutation, according to Dr. Kindler, lead author of the POLO trial.

The phase 3 study by Dr. Kindler and colleagues included 247 patients with metastatic pancreatic cancer and germline BRCA1/BRCA2 mutations who received at least 16 weeks of platinum-based chemotherapy.

Thirty-eight percent of enrolled patients had disease progression, declined randomization, or were ineligible to continue, Dr. Kindler said. The remaining 154 patients were randomized 3:2 to receive olaparib 300 mg twice daily or placebo.

The primary end point of the study was progression-free survival measured from the time of randomization. The median progression-free survival of 7.4 versus 3.8 months for olaparib and placebo, respectively, represented a 47% decrease in risk of progression or death (HR, 0.53; P = .0038), Dr. Kindler reported at the meeting.

“What is truly remarkable is that the median duration of response to olaparib in these patients who had metastatic pancreatic cancer was more than 2 years,” she said in the press conference. Specifically, median duration of response was 24.9 months and 3.7 months for olaparib and placebo arms, respectively.

There was no difference in overall survival between olaparib and placebo arms in the interim analysis. Final overall survival results will be evaluated when the data are more mature, Dr. Kindler said.

Olaparib treatment was well tolerated and had an adverse event profile similar to what has been observed in other tumor types, according to Dr. Kindler, who added that health-related quality of life was not different between the PARP inhibitor and placebo arms of the trial.

While longer-term data are awaited to understand the full impact of the results, the POLO study already represents a “huge step forward” in the treatment of metastatic pancreatic cancer, said Dr. Cole, the ASCO expert.

“It is our duty to search for this genetic mutation in all patients with metastatic pancreatic cancer, so we can identify those people who have the BRCA mutation and can benefit from being treated with an oral agent that can extend their life,” she said at the press conference.

Funding for the study came from AstraZeneca and Merck Sharp & Dohme Corp. Dr. Kindler provided disclosures related to Aduro Biotech, Aldeyra Therapeutics, Astellas Pharma, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Deciphera, ERYTECH Pharma, Five Prime Therapeutics, GlaxoSmithKline, Inhibrx, ipsen, Kyowa Hakko Kirin, Lilly, MedImmune, Merck, Paradox Therapeutics, Polaris, Roche/Genentech, and Verastem.

SOURCE: Kindler HL, et al. ASCO 2019. Abstract LBA4.

CHICAGO – In patients with metastatic pancreatic cancer and a germline BRCA mutation, maintenance treatment with olaparib resulted in significant and clinically meaningful improvements in progression-free survival in a phase 3 trial, an investigator reported.

For patients who completed chemotherapy and went on to receive the PARP inhibitor, median progression-free survival was 7.4 months, versus just 3.8 months for placebo-treated patients in the phase 3 POLO study, said Hedy L. Kindler, MD, professor of medicine with University of Chicago Medicine.

“A strategic approach of first-line platinum based chemo followed by maintenance olaparib treatment should become a new standard of care for patients with metastatic pancreatic cancer who have a germ line BRCA mutation,” Dr. Kindler said here in a press conference at the annual meeting of the American Society of Clinical Oncology.

This phase 3 study is the first to show that treatment of metastatic pancreatic cancer can be tailored based on a biomarker, highlights the importance of germline BRCA mutation testing, according to ASCO expert Suzanne Cole, MD.

“I think this is practice-changing for people who have BRCA mutations,” Dr. Cole said in the press conference. “I can’t wait to go back to clinic on Tuesday and look for it in my own patients.”

Four to seven percent of patients with pancreatic cancer harbor a germline BRCA1 or BRCA2 mutation, according to Dr. Kindler, lead author of the POLO trial.

The phase 3 study by Dr. Kindler and colleagues included 247 patients with metastatic pancreatic cancer and germline BRCA1/BRCA2 mutations who received at least 16 weeks of platinum-based chemotherapy.

Thirty-eight percent of enrolled patients had disease progression, declined randomization, or were ineligible to continue, Dr. Kindler said. The remaining 154 patients were randomized 3:2 to receive olaparib 300 mg twice daily or placebo.

The primary end point of the study was progression-free survival measured from the time of randomization. The median progression-free survival of 7.4 versus 3.8 months for olaparib and placebo, respectively, represented a 47% decrease in risk of progression or death (HR, 0.53; P = .0038), Dr. Kindler reported at the meeting.

“What is truly remarkable is that the median duration of response to olaparib in these patients who had metastatic pancreatic cancer was more than 2 years,” she said in the press conference. Specifically, median duration of response was 24.9 months and 3.7 months for olaparib and placebo arms, respectively.

There was no difference in overall survival between olaparib and placebo arms in the interim analysis. Final overall survival results will be evaluated when the data are more mature, Dr. Kindler said.

Olaparib treatment was well tolerated and had an adverse event profile similar to what has been observed in other tumor types, according to Dr. Kindler, who added that health-related quality of life was not different between the PARP inhibitor and placebo arms of the trial.

While longer-term data are awaited to understand the full impact of the results, the POLO study already represents a “huge step forward” in the treatment of metastatic pancreatic cancer, said Dr. Cole, the ASCO expert.

“It is our duty to search for this genetic mutation in all patients with metastatic pancreatic cancer, so we can identify those people who have the BRCA mutation and can benefit from being treated with an oral agent that can extend their life,” she said at the press conference.

Funding for the study came from AstraZeneca and Merck Sharp & Dohme Corp. Dr. Kindler provided disclosures related to Aduro Biotech, Aldeyra Therapeutics, Astellas Pharma, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Deciphera, ERYTECH Pharma, Five Prime Therapeutics, GlaxoSmithKline, Inhibrx, ipsen, Kyowa Hakko Kirin, Lilly, MedImmune, Merck, Paradox Therapeutics, Polaris, Roche/Genentech, and Verastem.

SOURCE: Kindler HL, et al. ASCO 2019. Abstract LBA4.

CHICAGO – In patients with metastatic pancreatic cancer and a germline BRCA mutation, maintenance treatment with olaparib resulted in significant and clinically meaningful improvements in progression-free survival in a phase 3 trial, an investigator reported.

For patients who completed chemotherapy and went on to receive the PARP inhibitor, median progression-free survival was 7.4 months, versus just 3.8 months for placebo-treated patients in the phase 3 POLO study, said Hedy L. Kindler, MD, professor of medicine with University of Chicago Medicine.

“A strategic approach of first-line platinum based chemo followed by maintenance olaparib treatment should become a new standard of care for patients with metastatic pancreatic cancer who have a germ line BRCA mutation,” Dr. Kindler said here in a press conference at the annual meeting of the American Society of Clinical Oncology.

This phase 3 study is the first to show that treatment of metastatic pancreatic cancer can be tailored based on a biomarker, highlights the importance of germline BRCA mutation testing, according to ASCO expert Suzanne Cole, MD.

“I think this is practice-changing for people who have BRCA mutations,” Dr. Cole said in the press conference. “I can’t wait to go back to clinic on Tuesday and look for it in my own patients.”

Four to seven percent of patients with pancreatic cancer harbor a germline BRCA1 or BRCA2 mutation, according to Dr. Kindler, lead author of the POLO trial.

The phase 3 study by Dr. Kindler and colleagues included 247 patients with metastatic pancreatic cancer and germline BRCA1/BRCA2 mutations who received at least 16 weeks of platinum-based chemotherapy.

Thirty-eight percent of enrolled patients had disease progression, declined randomization, or were ineligible to continue, Dr. Kindler said. The remaining 154 patients were randomized 3:2 to receive olaparib 300 mg twice daily or placebo.

The primary end point of the study was progression-free survival measured from the time of randomization. The median progression-free survival of 7.4 versus 3.8 months for olaparib and placebo, respectively, represented a 47% decrease in risk of progression or death (HR, 0.53; P = .0038), Dr. Kindler reported at the meeting.

“What is truly remarkable is that the median duration of response to olaparib in these patients who had metastatic pancreatic cancer was more than 2 years,” she said in the press conference. Specifically, median duration of response was 24.9 months and 3.7 months for olaparib and placebo arms, respectively.

There was no difference in overall survival between olaparib and placebo arms in the interim analysis. Final overall survival results will be evaluated when the data are more mature, Dr. Kindler said.

Olaparib treatment was well tolerated and had an adverse event profile similar to what has been observed in other tumor types, according to Dr. Kindler, who added that health-related quality of life was not different between the PARP inhibitor and placebo arms of the trial.

While longer-term data are awaited to understand the full impact of the results, the POLO study already represents a “huge step forward” in the treatment of metastatic pancreatic cancer, said Dr. Cole, the ASCO expert.

“It is our duty to search for this genetic mutation in all patients with metastatic pancreatic cancer, so we can identify those people who have the BRCA mutation and can benefit from being treated with an oral agent that can extend their life,” she said at the press conference.

Funding for the study came from AstraZeneca and Merck Sharp & Dohme Corp. Dr. Kindler provided disclosures related to Aduro Biotech, Aldeyra Therapeutics, Astellas Pharma, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Deciphera, ERYTECH Pharma, Five Prime Therapeutics, GlaxoSmithKline, Inhibrx, ipsen, Kyowa Hakko Kirin, Lilly, MedImmune, Merck, Paradox Therapeutics, Polaris, Roche/Genentech, and Verastem.

SOURCE: Kindler HL, et al. ASCO 2019. Abstract LBA4.

CHICAGO – Adding the androgen-binding inhibitor apalutamide to androgen deprivation therapy (ADT) significantly increased radiographic progression-free survival and overall survival in men with metastatic castration-sensitive prostate cancer (mCSPC) compared with ADT alone in the phase 3 TITAN trial.

Neil Osterweil/MDedge News

Among 1052 patients randomized to apalutamide (Erleada) plus either ADT or placebo, the overall survival rate at 24 months was 82.4% in the apalutamide group, compared with 73.5% in the placebo group, translating into a hazard ratio for death with apalutamide of 0.67 (P = .005), reported Kim N. Chi, MD, from the BC Cancer and Vancouver Prostate Centre in Vancouver, British Columbia, Canada.

“The TITAN study met its dual primary end points, demonstrating significant benefits with apalutamide plus ADT in an all-comer mCSPC population. There were significant improvements in overall survival with a 33% reduction in the risk of death. There was also a significant improvement in radiographic progression-free survival with a 52% reduction in the risk of progression or death,” he said at the American Society of Clinical Oncology annual meeting.

The study was also published online in the New England Journal of Medicine to coincide with Dr. Chi’s presentation.

The TITAN (Targeted Investigational Treatment Analysis of Novel Anti-androgen) study was designed to evaluate apalutamide vs. placebo in a broad population of patients with mCSPC treated with continuous ADT.

“The rationale behind the TITAN study was that direct inhibition of the androgen receptor by apalutamide will provide a more complete reduction of androgen signaling than ADT alone, leading to improved clinical outcomes,” Dr. Chi said.

The investigators enrolled a total of 1052 men with castration-sensitive prostate cancer, distant metastatic disease manifested as one or more lesions on bone scans, and Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

All patients were on continuous ADT. Prior therapies allowed under the protocol included docetaxel for a maximum of 6 cycles with no evidence of progression during treatment or before randomization, ADT for not more than 6 months for mCSPC or not more than 3 years for localized prostate cancer, one course of radiation of surgery for symptoms associated with metastatic disease, or other localized treatments completed at least 1 year before randomization.

The median patient age was 68 years. In all 62.7% of patients had high-volume disease, and the remainder had low-volume disease.

In this, the first interim analysis conducted at a median follow-up of 22.7 months, the 68.2% of patients in the apalutamide group had radiographic PFS, compared with 47.5% in the placebo group. The hazard ratio for progression or death with apalutamide was 0.48 (P less than .001).

As noted before, 24-month overall survival rates were 82.4% vs. 73.5%, respectively.

The secondary endpoint of median time to cytotoxic chemotherapy also significantly favored apalutamide, with a hazard ratio of 0.39 (P less than .0001). Other secondary endpoints, including median time to pain progression, median time to chronic opioid use, and median time to skeletal-related events trended in favor of apalutamide but were not statistically significant.

Grade 3 or 4 adverse events occurred in 42.2% of patients in the apalutamide arm and 40.8% in the placebo arm. The incidence of any serious adverse event was 19.8% with apalutamide and 20.3% with placebo. Adverse events leading to discontinuation occurred in 8% and 5.3%, respectively, and adverse events leading to death occurred in 1.9% vs. 3.0%.

Apalutamide was associated with higher incidences of rash, fatigue, hypothyroidism, and fracture.

The study results show that “androgen deprivation therapy and apalutamide for metastatic hormone-sensitive prostate cancer improves survival, and thus reinforces the current practice of ADT plus a single agent, whether it be docetaxel, abiraterone, enzalutamide, and now apalutamide,” commented Michael A. Carducci, MD, from the Johns Hopkins Sidney Kimmel Cancer Center in Baltimore, the invited discussant.

Neil Osterweil/MDedge News

Metastatic castration-sensitive prostate cancer is a broadly heterogeneous disease state, and the treatment benefits offered with various drugs is not consistent in subsets of patients. Investigators need to develop better molecularly based methods, combined with cliniopathologic factors, to better determine which subgroups of patients can benefit from specific drugs, he said.

The TITAN trial was supported by Aragon Pharmaceuticals. Dr. Chi disclosed grants and personal fees from multiple companies, not including Aragon. Dr. Carducci disclosed consulting or advisory roles and institutional research funding from multiple companies, not including Aragon.

SOURCE: Chi KN, ASCO 2019 Abstract 5006. N Engl J Med doi: 10.1056/NEJMoa1903307 .

CHICAGO – Adding the androgen-binding inhibitor apalutamide to androgen deprivation therapy (ADT) significantly increased radiographic progression-free survival and overall survival in men with metastatic castration-sensitive prostate cancer (mCSPC) compared with ADT alone in the phase 3 TITAN trial.

Neil Osterweil/MDedge News

Among 1052 patients randomized to apalutamide (Erleada) plus either ADT or placebo, the overall survival rate at 24 months was 82.4% in the apalutamide group, compared with 73.5% in the placebo group, translating into a hazard ratio for death with apalutamide of 0.67 (P = .005), reported Kim N. Chi, MD, from the BC Cancer and Vancouver Prostate Centre in Vancouver, British Columbia, Canada.

“The TITAN study met its dual primary end points, demonstrating significant benefits with apalutamide plus ADT in an all-comer mCSPC population. There were significant improvements in overall survival with a 33% reduction in the risk of death. There was also a significant improvement in radiographic progression-free survival with a 52% reduction in the risk of progression or death,” he said at the American Society of Clinical Oncology annual meeting.

The study was also published online in the New England Journal of Medicine to coincide with Dr. Chi’s presentation.

The TITAN (Targeted Investigational Treatment Analysis of Novel Anti-androgen) study was designed to evaluate apalutamide vs. placebo in a broad population of patients with mCSPC treated with continuous ADT.

“The rationale behind the TITAN study was that direct inhibition of the androgen receptor by apalutamide will provide a more complete reduction of androgen signaling than ADT alone, leading to improved clinical outcomes,” Dr. Chi said.

The investigators enrolled a total of 1052 men with castration-sensitive prostate cancer, distant metastatic disease manifested as one or more lesions on bone scans, and Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

All patients were on continuous ADT. Prior therapies allowed under the protocol included docetaxel for a maximum of 6 cycles with no evidence of progression during treatment or before randomization, ADT for not more than 6 months for mCSPC or not more than 3 years for localized prostate cancer, one course of radiation of surgery for symptoms associated with metastatic disease, or other localized treatments completed at least 1 year before randomization.

The median patient age was 68 years. In all 62.7% of patients had high-volume disease, and the remainder had low-volume disease.

In this, the first interim analysis conducted at a median follow-up of 22.7 months, the 68.2% of patients in the apalutamide group had radiographic PFS, compared with 47.5% in the placebo group. The hazard ratio for progression or death with apalutamide was 0.48 (P less than .001).

As noted before, 24-month overall survival rates were 82.4% vs. 73.5%, respectively.

The secondary endpoint of median time to cytotoxic chemotherapy also significantly favored apalutamide, with a hazard ratio of 0.39 (P less than .0001). Other secondary endpoints, including median time to pain progression, median time to chronic opioid use, and median time to skeletal-related events trended in favor of apalutamide but were not statistically significant.

Grade 3 or 4 adverse events occurred in 42.2% of patients in the apalutamide arm and 40.8% in the placebo arm. The incidence of any serious adverse event was 19.8% with apalutamide and 20.3% with placebo. Adverse events leading to discontinuation occurred in 8% and 5.3%, respectively, and adverse events leading to death occurred in 1.9% vs. 3.0%.

Apalutamide was associated with higher incidences of rash, fatigue, hypothyroidism, and fracture.

The study results show that “androgen deprivation therapy and apalutamide for metastatic hormone-sensitive prostate cancer improves survival, and thus reinforces the current practice of ADT plus a single agent, whether it be docetaxel, abiraterone, enzalutamide, and now apalutamide,” commented Michael A. Carducci, MD, from the Johns Hopkins Sidney Kimmel Cancer Center in Baltimore, the invited discussant.

Neil Osterweil/MDedge News

Metastatic castration-sensitive prostate cancer is a broadly heterogeneous disease state, and the treatment benefits offered with various drugs is not consistent in subsets of patients. Investigators need to develop better molecularly based methods, combined with cliniopathologic factors, to better determine which subgroups of patients can benefit from specific drugs, he said.

The TITAN trial was supported by Aragon Pharmaceuticals. Dr. Chi disclosed grants and personal fees from multiple companies, not including Aragon. Dr. Carducci disclosed consulting or advisory roles and institutional research funding from multiple companies, not including Aragon.

SOURCE: Chi KN, ASCO 2019 Abstract 5006. N Engl J Med doi: 10.1056/NEJMoa1903307 .

CHICAGO – Adding the androgen-binding inhibitor apalutamide to androgen deprivation therapy (ADT) significantly increased radiographic progression-free survival and overall survival in men with metastatic castration-sensitive prostate cancer (mCSPC) compared with ADT alone in the phase 3 TITAN trial.

Neil Osterweil/MDedge News

Among 1052 patients randomized to apalutamide (Erleada) plus either ADT or placebo, the overall survival rate at 24 months was 82.4% in the apalutamide group, compared with 73.5% in the placebo group, translating into a hazard ratio for death with apalutamide of 0.67 (P = .005), reported Kim N. Chi, MD, from the BC Cancer and Vancouver Prostate Centre in Vancouver, British Columbia, Canada.

“The TITAN study met its dual primary end points, demonstrating significant benefits with apalutamide plus ADT in an all-comer mCSPC population. There were significant improvements in overall survival with a 33% reduction in the risk of death. There was also a significant improvement in radiographic progression-free survival with a 52% reduction in the risk of progression or death,” he said at the American Society of Clinical Oncology annual meeting.

The study was also published online in the New England Journal of Medicine to coincide with Dr. Chi’s presentation.

The TITAN (Targeted Investigational Treatment Analysis of Novel Anti-androgen) study was designed to evaluate apalutamide vs. placebo in a broad population of patients with mCSPC treated with continuous ADT.

“The rationale behind the TITAN study was that direct inhibition of the androgen receptor by apalutamide will provide a more complete reduction of androgen signaling than ADT alone, leading to improved clinical outcomes,” Dr. Chi said.

The investigators enrolled a total of 1052 men with castration-sensitive prostate cancer, distant metastatic disease manifested as one or more lesions on bone scans, and Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

All patients were on continuous ADT. Prior therapies allowed under the protocol included docetaxel for a maximum of 6 cycles with no evidence of progression during treatment or before randomization, ADT for not more than 6 months for mCSPC or not more than 3 years for localized prostate cancer, one course of radiation of surgery for symptoms associated with metastatic disease, or other localized treatments completed at least 1 year before randomization.

The median patient age was 68 years. In all 62.7% of patients had high-volume disease, and the remainder had low-volume disease.

In this, the first interim analysis conducted at a median follow-up of 22.7 months, the 68.2% of patients in the apalutamide group had radiographic PFS, compared with 47.5% in the placebo group. The hazard ratio for progression or death with apalutamide was 0.48 (P less than .001).

As noted before, 24-month overall survival rates were 82.4% vs. 73.5%, respectively.

The secondary endpoint of median time to cytotoxic chemotherapy also significantly favored apalutamide, with a hazard ratio of 0.39 (P less than .0001). Other secondary endpoints, including median time to pain progression, median time to chronic opioid use, and median time to skeletal-related events trended in favor of apalutamide but were not statistically significant.

Grade 3 or 4 adverse events occurred in 42.2% of patients in the apalutamide arm and 40.8% in the placebo arm. The incidence of any serious adverse event was 19.8% with apalutamide and 20.3% with placebo. Adverse events leading to discontinuation occurred in 8% and 5.3%, respectively, and adverse events leading to death occurred in 1.9% vs. 3.0%.

Apalutamide was associated with higher incidences of rash, fatigue, hypothyroidism, and fracture.

The study results show that “androgen deprivation therapy and apalutamide for metastatic hormone-sensitive prostate cancer improves survival, and thus reinforces the current practice of ADT plus a single agent, whether it be docetaxel, abiraterone, enzalutamide, and now apalutamide,” commented Michael A. Carducci, MD, from the Johns Hopkins Sidney Kimmel Cancer Center in Baltimore, the invited discussant.

Neil Osterweil/MDedge News

Metastatic castration-sensitive prostate cancer is a broadly heterogeneous disease state, and the treatment benefits offered with various drugs is not consistent in subsets of patients. Investigators need to develop better molecularly based methods, combined with cliniopathologic factors, to better determine which subgroups of patients can benefit from specific drugs, he said.

The TITAN trial was supported by Aragon Pharmaceuticals. Dr. Chi disclosed grants and personal fees from multiple companies, not including Aragon. Dr. Carducci disclosed consulting or advisory roles and institutional research funding from multiple companies, not including Aragon.

SOURCE: Chi KN, ASCO 2019 Abstract 5006. N Engl J Med doi: 10.1056/NEJMoa1903307 .