Andrew D. Bowser

CHICAGO – Oxaliplatin/5-fluorouracil is the new benchmark for previously treated advanced biliary tract cancers, though more research is needed to improve outcomes, an investigator said at the annual meeting of the American Society of Clinical Oncology.

Modified FOLFOX (mFOLFOX) added to active symptom control reduced risk of death by 31% versus active symptom control alone in patients who had progressed following standard cisplatin/gemcitabine chemotherapy, according to Angela Lamarca, MD, PhD, of the University of Manchester, England, who presented results in an oral presentation at the meeting.

While the chemotherapy did improve survival versus no chemotherapy, the overall benefit was modest and the toxicity was moderate, William P. Harris, MD, said in a discussion of the study results.

“At the moment, based on this study, I think that FOLFOX is the benchmark moving forward in the second-line setting, but certainly clinical trials are reasonable in this space,” said Dr. Harris, who is with the University of Washington and Fred Hutchinson Cancer Research Center, Seattle.

Novel therapies seem particularly “appealing” in biliary tract cancers, he said, based on results so far from studies that include inhibitors targeting PD-1, FGFR1-3, and IDH1, among others.

The present study, known as ABC-06, was the first-ever prospective phase 3 trial to evaluate the benefit of additional chemotherapy after cisplatin/gemcitabine in patients biliary tract cancers, Dr. Lamarca said.

While cisplatin plus gemcitabine is established as first-line therapy for advanced biliary tract cancers, the role of second-line chemotherapy has been unclear, she said in her presentation.

In the trial initiated by Dr. Lamarca and colleagues, 162 patients were randomized to active symptom control alone, or active symptom control plus modified FOLFOX chemotherapy given every 14 days for up to 12 cycles.

The rate of grade 3-4 adverse events was 59% in the modified FOLFOX arm versus 40% in the active symptom control arm. There were three chemotherapy-related deaths, due respectively to renal failure, febrile neutropenia, and acute kidney injury, according to the report.

Grade 3-4 fatigue, infections, and decreased neutrophil count were more common in the chemotherapy arm, while anorexia and thromboembolic events were more often seen in the group of patients receiving active symptom control alone, Dr. Lamarca said.

The study’s primary endpoint of overall survival was met, with a hazard ratio of 0.69 (95% CI, 0.50-0.97; P = .031) favoring the chemotherapy arm after adjusting for platinum sensitivity, albumin, and stage.

The difference in median overall survival was “modest,” Dr. Lamarca said, at 6.2 months in the modified FOLFOX arm versus a higher-than-expected 5.3 months in the active symptom control arm (investigators had anticipated a median survival of 4 months).

However, “clinically meaningful” increases were seen with FOLFOX in both the 6-month overall survival rate, at 50.6% versus 35.5%, and the 12-month overall survival rate, at 25.9% versus 11.4% she said in her presentation.

“Modified FOLFOX chemotherapy combined with active symptom control should therefore become the standard of care in the second-line setting for patients with advanced biliary tract cancers,” she said.

Dr. Lamarca reported disclosures related to Eisai, Nutricia, Ipsen, Merck, Novartis, Pfizer, Abbott Nutrition, Advanced Accelerator Applications, Bayer, Celgene, Delcath Systems, Mylan, NanoString Technologies, and Sirtex Medical.

SOURCE: Lamarca A et al. ASCO 2019, Abstract 4003.

CHICAGO – Oxaliplatin/5-fluorouracil is the new benchmark for previously treated advanced biliary tract cancers, though more research is needed to improve outcomes, an investigator said at the annual meeting of the American Society of Clinical Oncology.

Modified FOLFOX (mFOLFOX) added to active symptom control reduced risk of death by 31% versus active symptom control alone in patients who had progressed following standard cisplatin/gemcitabine chemotherapy, according to Angela Lamarca, MD, PhD, of the University of Manchester, England, who presented results in an oral presentation at the meeting.

While the chemotherapy did improve survival versus no chemotherapy, the overall benefit was modest and the toxicity was moderate, William P. Harris, MD, said in a discussion of the study results.

“At the moment, based on this study, I think that FOLFOX is the benchmark moving forward in the second-line setting, but certainly clinical trials are reasonable in this space,” said Dr. Harris, who is with the University of Washington and Fred Hutchinson Cancer Research Center, Seattle.

Novel therapies seem particularly “appealing” in biliary tract cancers, he said, based on results so far from studies that include inhibitors targeting PD-1, FGFR1-3, and IDH1, among others.

The present study, known as ABC-06, was the first-ever prospective phase 3 trial to evaluate the benefit of additional chemotherapy after cisplatin/gemcitabine in patients biliary tract cancers, Dr. Lamarca said.

While cisplatin plus gemcitabine is established as first-line therapy for advanced biliary tract cancers, the role of second-line chemotherapy has been unclear, she said in her presentation.

In the trial initiated by Dr. Lamarca and colleagues, 162 patients were randomized to active symptom control alone, or active symptom control plus modified FOLFOX chemotherapy given every 14 days for up to 12 cycles.

The rate of grade 3-4 adverse events was 59% in the modified FOLFOX arm versus 40% in the active symptom control arm. There were three chemotherapy-related deaths, due respectively to renal failure, febrile neutropenia, and acute kidney injury, according to the report.

Grade 3-4 fatigue, infections, and decreased neutrophil count were more common in the chemotherapy arm, while anorexia and thromboembolic events were more often seen in the group of patients receiving active symptom control alone, Dr. Lamarca said.

The study’s primary endpoint of overall survival was met, with a hazard ratio of 0.69 (95% CI, 0.50-0.97; P = .031) favoring the chemotherapy arm after adjusting for platinum sensitivity, albumin, and stage.

The difference in median overall survival was “modest,” Dr. Lamarca said, at 6.2 months in the modified FOLFOX arm versus a higher-than-expected 5.3 months in the active symptom control arm (investigators had anticipated a median survival of 4 months).

However, “clinically meaningful” increases were seen with FOLFOX in both the 6-month overall survival rate, at 50.6% versus 35.5%, and the 12-month overall survival rate, at 25.9% versus 11.4% she said in her presentation.

“Modified FOLFOX chemotherapy combined with active symptom control should therefore become the standard of care in the second-line setting for patients with advanced biliary tract cancers,” she said.

Dr. Lamarca reported disclosures related to Eisai, Nutricia, Ipsen, Merck, Novartis, Pfizer, Abbott Nutrition, Advanced Accelerator Applications, Bayer, Celgene, Delcath Systems, Mylan, NanoString Technologies, and Sirtex Medical.

SOURCE: Lamarca A et al. ASCO 2019, Abstract 4003.

CHICAGO – Oxaliplatin/5-fluorouracil is the new benchmark for previously treated advanced biliary tract cancers, though more research is needed to improve outcomes, an investigator said at the annual meeting of the American Society of Clinical Oncology.

Modified FOLFOX (mFOLFOX) added to active symptom control reduced risk of death by 31% versus active symptom control alone in patients who had progressed following standard cisplatin/gemcitabine chemotherapy, according to Angela Lamarca, MD, PhD, of the University of Manchester, England, who presented results in an oral presentation at the meeting.

While the chemotherapy did improve survival versus no chemotherapy, the overall benefit was modest and the toxicity was moderate, William P. Harris, MD, said in a discussion of the study results.

“At the moment, based on this study, I think that FOLFOX is the benchmark moving forward in the second-line setting, but certainly clinical trials are reasonable in this space,” said Dr. Harris, who is with the University of Washington and Fred Hutchinson Cancer Research Center, Seattle.

Novel therapies seem particularly “appealing” in biliary tract cancers, he said, based on results so far from studies that include inhibitors targeting PD-1, FGFR1-3, and IDH1, among others.

The present study, known as ABC-06, was the first-ever prospective phase 3 trial to evaluate the benefit of additional chemotherapy after cisplatin/gemcitabine in patients biliary tract cancers, Dr. Lamarca said.

While cisplatin plus gemcitabine is established as first-line therapy for advanced biliary tract cancers, the role of second-line chemotherapy has been unclear, she said in her presentation.

In the trial initiated by Dr. Lamarca and colleagues, 162 patients were randomized to active symptom control alone, or active symptom control plus modified FOLFOX chemotherapy given every 14 days for up to 12 cycles.

The rate of grade 3-4 adverse events was 59% in the modified FOLFOX arm versus 40% in the active symptom control arm. There were three chemotherapy-related deaths, due respectively to renal failure, febrile neutropenia, and acute kidney injury, according to the report.

Grade 3-4 fatigue, infections, and decreased neutrophil count were more common in the chemotherapy arm, while anorexia and thromboembolic events were more often seen in the group of patients receiving active symptom control alone, Dr. Lamarca said.

The study’s primary endpoint of overall survival was met, with a hazard ratio of 0.69 (95% CI, 0.50-0.97; P = .031) favoring the chemotherapy arm after adjusting for platinum sensitivity, albumin, and stage.

The difference in median overall survival was “modest,” Dr. Lamarca said, at 6.2 months in the modified FOLFOX arm versus a higher-than-expected 5.3 months in the active symptom control arm (investigators had anticipated a median survival of 4 months).

However, “clinically meaningful” increases were seen with FOLFOX in both the 6-month overall survival rate, at 50.6% versus 35.5%, and the 12-month overall survival rate, at 25.9% versus 11.4% she said in her presentation.

“Modified FOLFOX chemotherapy combined with active symptom control should therefore become the standard of care in the second-line setting for patients with advanced biliary tract cancers,” she said.

Dr. Lamarca reported disclosures related to Eisai, Nutricia, Ipsen, Merck, Novartis, Pfizer, Abbott Nutrition, Advanced Accelerator Applications, Bayer, Celgene, Delcath Systems, Mylan, NanoString Technologies, and Sirtex Medical.

SOURCE: Lamarca A et al. ASCO 2019, Abstract 4003.

CHICAGO – Pazopanib significantly improved progression-free survival (PFS) in patients with progressive carcinoid tumors who were enrolled in a prospective randomized phase 2 trial.*

Median PFS was 11.6 months for patients receiving the small molecule VEGF inhibitor, versus 8.5 months for those receiving placebo (P = .0005), according to results of the Alliance A021202 trial.

This is the first randomized study to show that the vascular endothelial growth factor (VEGF) pathway may be a valid therapeutic target in carcinoid tumors, said investigator Emily K. Bergsland, MD, of the University of California, San Francisco.

However, the potential benefits of pazopanib need to be viewed in light of toxicity risks, including an excess of hypertension, Dr. Bergsland said in an oral abstract presentation at the annual meeting of the American Society of Clinical Oncology.

The efficacy results suggest that pazopanib is another promising systemic option for carcinoid tumors, according to William P. Harris, MD, of the University of Washington and Fred Hutchinson Cancer Research Center, Seattle.

“Pazopanib does inhibit other targets, including [fibroblast growth factor receptors], which may be of relevance in carcinoid,” Dr. Harris noted in a podium discussion of the A021202 trial results.

Other promising systemic options under investigation include cabozantinib, which he said will be evaluated in phase 3 trials, lenvatinib, and ramucirumab plus a somatostatin analogue.

The CDK4/6 inhibition is of interest and will be pursued in future trials, though unfortunately the role of checkpoint inhibitors is “unclear” in this tumor type, he said.

In the present randomized study of pazopanib, a computer error resulted in slightly more patients being randomized to the pazopanib arm – 89 patients – while 72 were randomized to placebo, according to the investigator.

The rate of grade 3 or greater toxicities was 73.0% for pazopanib, and 7.9% for placebo in the study. Notably, there was a relatively high rate of grade 3 or greater hypertension, at 26.9% versus 4.2% for placebo, though only one case in the pazopanib arm was grade 4, Dr. Bergsland said.

Pazopanib was also associated with more symptoms such as diarrhea, appetite loss, and fatigue, but the overall quality of life was similar between the groups in preliminary analyses, said Dr. Bergsland.

Despite the improved PFS in the pazopanib arm, there was no improvement in overall survival. That’s likely because placebo-treated patients were allowed to cross over to pazopanib upon progression, and two-thirds of them did so, said Dr. Bergsland. The resulting median overall survival was 41.3 months for pazopanib and 42.4 months for placebo.

“Additional work is needed to identify strategies for mitigating toxicity and/or selecting patients most likely to benefit,” Dr. Bergsland said in her presentation.

Toward that end, investigators are looking at strategies including angiome profiling, assessment of tumor growth rate, and textural image analysis, she added.

Dr. Bergsland reported disclosures related to More Health, UpToDate, Advanced Accelerator Applications, Lexicon, Merck, and Novartis.

SOURCE: Bergsland EK, et al. ASCO 2019. Abstract 4005.

Correction, 6/17/19: An earlier version of this article mischaracterized the study type.

CHICAGO – Pazopanib significantly improved progression-free survival (PFS) in patients with progressive carcinoid tumors who were enrolled in a prospective randomized phase 2 trial.*

Median PFS was 11.6 months for patients receiving the small molecule VEGF inhibitor, versus 8.5 months for those receiving placebo (P = .0005), according to results of the Alliance A021202 trial.

This is the first randomized study to show that the vascular endothelial growth factor (VEGF) pathway may be a valid therapeutic target in carcinoid tumors, said investigator Emily K. Bergsland, MD, of the University of California, San Francisco.

However, the potential benefits of pazopanib need to be viewed in light of toxicity risks, including an excess of hypertension, Dr. Bergsland said in an oral abstract presentation at the annual meeting of the American Society of Clinical Oncology.

The efficacy results suggest that pazopanib is another promising systemic option for carcinoid tumors, according to William P. Harris, MD, of the University of Washington and Fred Hutchinson Cancer Research Center, Seattle.

“Pazopanib does inhibit other targets, including [fibroblast growth factor receptors], which may be of relevance in carcinoid,” Dr. Harris noted in a podium discussion of the A021202 trial results.

Other promising systemic options under investigation include cabozantinib, which he said will be evaluated in phase 3 trials, lenvatinib, and ramucirumab plus a somatostatin analogue.

The CDK4/6 inhibition is of interest and will be pursued in future trials, though unfortunately the role of checkpoint inhibitors is “unclear” in this tumor type, he said.

In the present randomized study of pazopanib, a computer error resulted in slightly more patients being randomized to the pazopanib arm – 89 patients – while 72 were randomized to placebo, according to the investigator.

The rate of grade 3 or greater toxicities was 73.0% for pazopanib, and 7.9% for placebo in the study. Notably, there was a relatively high rate of grade 3 or greater hypertension, at 26.9% versus 4.2% for placebo, though only one case in the pazopanib arm was grade 4, Dr. Bergsland said.

Pazopanib was also associated with more symptoms such as diarrhea, appetite loss, and fatigue, but the overall quality of life was similar between the groups in preliminary analyses, said Dr. Bergsland.

Despite the improved PFS in the pazopanib arm, there was no improvement in overall survival. That’s likely because placebo-treated patients were allowed to cross over to pazopanib upon progression, and two-thirds of them did so, said Dr. Bergsland. The resulting median overall survival was 41.3 months for pazopanib and 42.4 months for placebo.

“Additional work is needed to identify strategies for mitigating toxicity and/or selecting patients most likely to benefit,” Dr. Bergsland said in her presentation.

Toward that end, investigators are looking at strategies including angiome profiling, assessment of tumor growth rate, and textural image analysis, she added.

Dr. Bergsland reported disclosures related to More Health, UpToDate, Advanced Accelerator Applications, Lexicon, Merck, and Novartis.

SOURCE: Bergsland EK, et al. ASCO 2019. Abstract 4005.

Correction, 6/17/19: An earlier version of this article mischaracterized the study type.

CHICAGO – Pazopanib significantly improved progression-free survival (PFS) in patients with progressive carcinoid tumors who were enrolled in a prospective randomized phase 2 trial.*

Median PFS was 11.6 months for patients receiving the small molecule VEGF inhibitor, versus 8.5 months for those receiving placebo (P = .0005), according to results of the Alliance A021202 trial.

This is the first randomized study to show that the vascular endothelial growth factor (VEGF) pathway may be a valid therapeutic target in carcinoid tumors, said investigator Emily K. Bergsland, MD, of the University of California, San Francisco.

However, the potential benefits of pazopanib need to be viewed in light of toxicity risks, including an excess of hypertension, Dr. Bergsland said in an oral abstract presentation at the annual meeting of the American Society of Clinical Oncology.

The efficacy results suggest that pazopanib is another promising systemic option for carcinoid tumors, according to William P. Harris, MD, of the University of Washington and Fred Hutchinson Cancer Research Center, Seattle.

“Pazopanib does inhibit other targets, including [fibroblast growth factor receptors], which may be of relevance in carcinoid,” Dr. Harris noted in a podium discussion of the A021202 trial results.

Other promising systemic options under investigation include cabozantinib, which he said will be evaluated in phase 3 trials, lenvatinib, and ramucirumab plus a somatostatin analogue.

The CDK4/6 inhibition is of interest and will be pursued in future trials, though unfortunately the role of checkpoint inhibitors is “unclear” in this tumor type, he said.

In the present randomized study of pazopanib, a computer error resulted in slightly more patients being randomized to the pazopanib arm – 89 patients – while 72 were randomized to placebo, according to the investigator.

The rate of grade 3 or greater toxicities was 73.0% for pazopanib, and 7.9% for placebo in the study. Notably, there was a relatively high rate of grade 3 or greater hypertension, at 26.9% versus 4.2% for placebo, though only one case in the pazopanib arm was grade 4, Dr. Bergsland said.

Pazopanib was also associated with more symptoms such as diarrhea, appetite loss, and fatigue, but the overall quality of life was similar between the groups in preliminary analyses, said Dr. Bergsland.

Despite the improved PFS in the pazopanib arm, there was no improvement in overall survival. That’s likely because placebo-treated patients were allowed to cross over to pazopanib upon progression, and two-thirds of them did so, said Dr. Bergsland. The resulting median overall survival was 41.3 months for pazopanib and 42.4 months for placebo.

“Additional work is needed to identify strategies for mitigating toxicity and/or selecting patients most likely to benefit,” Dr. Bergsland said in her presentation.

Toward that end, investigators are looking at strategies including angiome profiling, assessment of tumor growth rate, and textural image analysis, she added.

Dr. Bergsland reported disclosures related to More Health, UpToDate, Advanced Accelerator Applications, Lexicon, Merck, and Novartis.

SOURCE: Bergsland EK, et al. ASCO 2019. Abstract 4005.

Correction, 6/17/19: An earlier version of this article mischaracterized the study type.

CHICAGO – While gemcitabine plus nab-paclitaxel did not extend independently assessed disease-free survival versus gemcitabine alone in a phase 3 pancreatic cancer study, overall survival data are “encouraging” thus far, and merit further follow-up, an investigator said at the annual meeting of the American Society of Clinical Oncology.

The APACT trial was the first adjuvant pancreatic cancer trial to use an endpoint of disease-free survival, independently assessed without knowledge of medical or clinical circumstances, said investigator Margaret A. Tempero, MD, director of the UCSF Pancreas Center, San Francisco.

With that specific method of assessment, median disease-free survival was 19.4 months for gemcitabine plus nab-paclitaxel versus 18.8 months for gemcitabine alone, a finding that had a “slight trend” in favor of the combination arm, Dr. Tempero said.

By contrast, a more standard investigator-assessed disease-free survival showed an improvement favoring gemcitabine plus nab-paclitaxel over gemcitabine alone, in line with preliminary overall survival data that also appear to show an advantage for the combination over gemcitabine, according to Dr. Tempero.

“We thought we were introducing more rigor into the trial, but I think we all recognize clinically that it is often difficult to differentiate or distinguish recurrence in the pancreatic bed from postsurgical changes,” she said in a discussion period, “but clearly, this is a lesson learned, and I think that would be helpful for the field going forward in avoiding that endpoint.”

Since the trial was launched, both modified FOLFIRINOX and gemcitabine plus capecitabine have become category 1 recommendations for adjuvant pancreatic cancer in clinical practice guidelines from the National Comprehensive Cancer Network.

The “jury is still out” on whether gemcitabine plus nab-paclitaxel will join that group, said Jiping Wang, MD, PhD, of Dana-Farber Cancer Institute, Boston, who discussed the results of the APACT trial in a podium presentation.

“We are still waiting for the final overall survival result of the APACT trial,” he said. “Hopefully, the nab-paclitaxel/gemcitabine combination provides an alternative treatment, especially for patients with R1 resection who cannot tolerate modified FOLFIRINOX.”

While gemcitabine plus capecitabine is a good choice for patients who aren’t able to tolerate modified FOLFIRINOX, available evidence suggests it may not benefit patients with R1 resection, according to Dr. Wang.

The phase 3 APACT trial included patients with surgically resected pancreatic cancer enrolled at 179 sites in 21 countries. A total of 866 patients were randomized 1:1 to receive gemcitabine plus nab-paclitaxel or gemcitabine alone for six cycles.

While median independently assessed disease-free survival was 19.4 months for gemcitabine/nab-paclitaxel and 18.8 months for gemcitabine (hazard ratio, 0.88; P = .1824), median investigator-assessed disease free survival was 16.6 months versus 13.7 months for those arms, respectively (HR, 0.82; P = .0168), according to reported results.

Median interim overall survival was 40.5 months for gemcitabine/nab-paclitaxel versus 36.2 months for gemcitabine (HR, 0.82; P = .045), though the presenter emphasized that longer follow-up is needed to clarify the role of this combination as adjuvant therapy for pancreatic adenocarcinoma.

“I don’t think it’s wrong in a patient who can’t tolerate modified FOLFIRINOX to use gemcitabine and nab-paclitaxel, but I’m not sure everybody would agree with that,” Dr. Tempero said after being asked in the study discussion period if she would advocate for use of this combination regimen in frail patients.

“I think when we get more mature overall survival data, it will be a lot easier to make those decisions,” she said.

Dr. Tempero reported disclosures related to Abbie, Advance Medical, Astellas Pharma, AstraZeneca, Bristol-Myers Squibb, BioPharm Communications, Celgene, CPRIT, EcoR1 Capital, Eisai, FibroGen, Halozyme, Ignyta, Immunovia, Merck, Pharmacyclics, Pharmacyte Biotech, and Tocagen.

SOURCE: Tempero MA, et al. ASCO 2019. Abstract 4000.

CHICAGO – While gemcitabine plus nab-paclitaxel did not extend independently assessed disease-free survival versus gemcitabine alone in a phase 3 pancreatic cancer study, overall survival data are “encouraging” thus far, and merit further follow-up, an investigator said at the annual meeting of the American Society of Clinical Oncology.

The APACT trial was the first adjuvant pancreatic cancer trial to use an endpoint of disease-free survival, independently assessed without knowledge of medical or clinical circumstances, said investigator Margaret A. Tempero, MD, director of the UCSF Pancreas Center, San Francisco.

With that specific method of assessment, median disease-free survival was 19.4 months for gemcitabine plus nab-paclitaxel versus 18.8 months for gemcitabine alone, a finding that had a “slight trend” in favor of the combination arm, Dr. Tempero said.

By contrast, a more standard investigator-assessed disease-free survival showed an improvement favoring gemcitabine plus nab-paclitaxel over gemcitabine alone, in line with preliminary overall survival data that also appear to show an advantage for the combination over gemcitabine, according to Dr. Tempero.

“We thought we were introducing more rigor into the trial, but I think we all recognize clinically that it is often difficult to differentiate or distinguish recurrence in the pancreatic bed from postsurgical changes,” she said in a discussion period, “but clearly, this is a lesson learned, and I think that would be helpful for the field going forward in avoiding that endpoint.”

Since the trial was launched, both modified FOLFIRINOX and gemcitabine plus capecitabine have become category 1 recommendations for adjuvant pancreatic cancer in clinical practice guidelines from the National Comprehensive Cancer Network.

The “jury is still out” on whether gemcitabine plus nab-paclitaxel will join that group, said Jiping Wang, MD, PhD, of Dana-Farber Cancer Institute, Boston, who discussed the results of the APACT trial in a podium presentation.

“We are still waiting for the final overall survival result of the APACT trial,” he said. “Hopefully, the nab-paclitaxel/gemcitabine combination provides an alternative treatment, especially for patients with R1 resection who cannot tolerate modified FOLFIRINOX.”

While gemcitabine plus capecitabine is a good choice for patients who aren’t able to tolerate modified FOLFIRINOX, available evidence suggests it may not benefit patients with R1 resection, according to Dr. Wang.

The phase 3 APACT trial included patients with surgically resected pancreatic cancer enrolled at 179 sites in 21 countries. A total of 866 patients were randomized 1:1 to receive gemcitabine plus nab-paclitaxel or gemcitabine alone for six cycles.

While median independently assessed disease-free survival was 19.4 months for gemcitabine/nab-paclitaxel and 18.8 months for gemcitabine (hazard ratio, 0.88; P = .1824), median investigator-assessed disease free survival was 16.6 months versus 13.7 months for those arms, respectively (HR, 0.82; P = .0168), according to reported results.

Median interim overall survival was 40.5 months for gemcitabine/nab-paclitaxel versus 36.2 months for gemcitabine (HR, 0.82; P = .045), though the presenter emphasized that longer follow-up is needed to clarify the role of this combination as adjuvant therapy for pancreatic adenocarcinoma.

“I don’t think it’s wrong in a patient who can’t tolerate modified FOLFIRINOX to use gemcitabine and nab-paclitaxel, but I’m not sure everybody would agree with that,” Dr. Tempero said after being asked in the study discussion period if she would advocate for use of this combination regimen in frail patients.

“I think when we get more mature overall survival data, it will be a lot easier to make those decisions,” she said.

Dr. Tempero reported disclosures related to Abbie, Advance Medical, Astellas Pharma, AstraZeneca, Bristol-Myers Squibb, BioPharm Communications, Celgene, CPRIT, EcoR1 Capital, Eisai, FibroGen, Halozyme, Ignyta, Immunovia, Merck, Pharmacyclics, Pharmacyte Biotech, and Tocagen.

SOURCE: Tempero MA, et al. ASCO 2019. Abstract 4000.

CHICAGO – While gemcitabine plus nab-paclitaxel did not extend independently assessed disease-free survival versus gemcitabine alone in a phase 3 pancreatic cancer study, overall survival data are “encouraging” thus far, and merit further follow-up, an investigator said at the annual meeting of the American Society of Clinical Oncology.

The APACT trial was the first adjuvant pancreatic cancer trial to use an endpoint of disease-free survival, independently assessed without knowledge of medical or clinical circumstances, said investigator Margaret A. Tempero, MD, director of the UCSF Pancreas Center, San Francisco.

With that specific method of assessment, median disease-free survival was 19.4 months for gemcitabine plus nab-paclitaxel versus 18.8 months for gemcitabine alone, a finding that had a “slight trend” in favor of the combination arm, Dr. Tempero said.

By contrast, a more standard investigator-assessed disease-free survival showed an improvement favoring gemcitabine plus nab-paclitaxel over gemcitabine alone, in line with preliminary overall survival data that also appear to show an advantage for the combination over gemcitabine, according to Dr. Tempero.

“We thought we were introducing more rigor into the trial, but I think we all recognize clinically that it is often difficult to differentiate or distinguish recurrence in the pancreatic bed from postsurgical changes,” she said in a discussion period, “but clearly, this is a lesson learned, and I think that would be helpful for the field going forward in avoiding that endpoint.”

Since the trial was launched, both modified FOLFIRINOX and gemcitabine plus capecitabine have become category 1 recommendations for adjuvant pancreatic cancer in clinical practice guidelines from the National Comprehensive Cancer Network.

The “jury is still out” on whether gemcitabine plus nab-paclitaxel will join that group, said Jiping Wang, MD, PhD, of Dana-Farber Cancer Institute, Boston, who discussed the results of the APACT trial in a podium presentation.

“We are still waiting for the final overall survival result of the APACT trial,” he said. “Hopefully, the nab-paclitaxel/gemcitabine combination provides an alternative treatment, especially for patients with R1 resection who cannot tolerate modified FOLFIRINOX.”

While gemcitabine plus capecitabine is a good choice for patients who aren’t able to tolerate modified FOLFIRINOX, available evidence suggests it may not benefit patients with R1 resection, according to Dr. Wang.

The phase 3 APACT trial included patients with surgically resected pancreatic cancer enrolled at 179 sites in 21 countries. A total of 866 patients were randomized 1:1 to receive gemcitabine plus nab-paclitaxel or gemcitabine alone for six cycles.

While median independently assessed disease-free survival was 19.4 months for gemcitabine/nab-paclitaxel and 18.8 months for gemcitabine (hazard ratio, 0.88; P = .1824), median investigator-assessed disease free survival was 16.6 months versus 13.7 months for those arms, respectively (HR, 0.82; P = .0168), according to reported results.

Median interim overall survival was 40.5 months for gemcitabine/nab-paclitaxel versus 36.2 months for gemcitabine (HR, 0.82; P = .045), though the presenter emphasized that longer follow-up is needed to clarify the role of this combination as adjuvant therapy for pancreatic adenocarcinoma.

“I don’t think it’s wrong in a patient who can’t tolerate modified FOLFIRINOX to use gemcitabine and nab-paclitaxel, but I’m not sure everybody would agree with that,” Dr. Tempero said after being asked in the study discussion period if she would advocate for use of this combination regimen in frail patients.

“I think when we get more mature overall survival data, it will be a lot easier to make those decisions,” she said.

Dr. Tempero reported disclosures related to Abbie, Advance Medical, Astellas Pharma, AstraZeneca, Bristol-Myers Squibb, BioPharm Communications, Celgene, CPRIT, EcoR1 Capital, Eisai, FibroGen, Halozyme, Ignyta, Immunovia, Merck, Pharmacyclics, Pharmacyte Biotech, and Tocagen.

SOURCE: Tempero MA, et al. ASCO 2019. Abstract 4000.

CHICAGO – While cytoreductive nephrectomy is generally still inadvisable in metastatic renal cell carcinoma patients who require medical therapy, an update of the CARMENA trial suggests the procedure may provide benefit for certain patients.

Patients with only one International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk factor may benefit from cytoreductive nephrectomy, said CARMENA investigator Arnaud Méjean, MD, PhD, in a presentation at the annual meeting of the American Society of Clinical Oncology.

Among patients in CARMENA treated with nephrectomy plus sunitinib, median overall survival was 31.4 months for those with just one risk factor, and 17.6 months for those with two or more (hazard ratio, 1.68; 95% confidence interval, 1.10-2.57; P = .01), suggesting the procedure was “detrimental” to perform in the presence of multiple risk factors, the investigator said.

By contrast, among patients treated with sunitinib alone, there was no significant difference in median overall survival for patients with one risk factor versus those with two or more risk factors, said Dr. Méjean, who is with the Hôpital Européen Georges-Pompidou and Paris Descartes University.

In another analysis of the data, delayed nephrectomy after initial systemic therapy was associated with long overall survival in good responders, supporting that approach as a “good therapeutic strategy,” he said.

Based on these results, Dr. Méjean told ASCO attendees he would “go back to the operating theater to operate just very selected patients.”

In a podium discussion, Alexander Kutikov, MD, FACS, said CARMENA makes it “undeniable” that up-front cytoreductive therapy should be applied to a “very select group” of patients.

While that select group may be defined as the one IMDC risk factor group, Dr. Kutkov said it is also appropriate to offer cytoreductive nephrectomy to carefully selected patients who do not need immediate systemic therapy.

“If the plan is to observe without systemic therapy, proceed with cytoreductive nephrectomy, and for everybody else, I think we take great caution in offering cytoreductive nephrectomy, because it absolutely can harm,” said Dr. Kutikov, professor and chief of urologic oncology at Fox Chase Cancer Center, Philadelphia.

The CARMENA update confirmed that, in general, cytoreductive nephrectomy should not be the standard of care, according to Dr. Méjean.

With follow-up of 61.5 months, or longer than what was previously reported for the 450-patient trial, cytoreductive nephrectomy followed by sunitinib was again found to be not superior to sunitinib alone, he said. Median overall survival was 15.6 months for the nephrectomy plus sunitinib arm versus 19.8 months for the sunitinib arm, showing that sunitinib alone was noninferior based on the statistical design of the trial (hazard ratio, 0.97; 95% CI, 0.79-1.19, with a fixed upper limit for noninferiority of 1.20).

Dr. Méjean reported disclosures related to Ipsen, Novartis, Pfizer, Bristol-Myers Squibb, Janssen, Sanofi and Roche.

SOURCE: Méjean A et al. ASCO 2019, Abstract 4508.

CHICAGO – While cytoreductive nephrectomy is generally still inadvisable in metastatic renal cell carcinoma patients who require medical therapy, an update of the CARMENA trial suggests the procedure may provide benefit for certain patients.

Patients with only one International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk factor may benefit from cytoreductive nephrectomy, said CARMENA investigator Arnaud Méjean, MD, PhD, in a presentation at the annual meeting of the American Society of Clinical Oncology.

Among patients in CARMENA treated with nephrectomy plus sunitinib, median overall survival was 31.4 months for those with just one risk factor, and 17.6 months for those with two or more (hazard ratio, 1.68; 95% confidence interval, 1.10-2.57; P = .01), suggesting the procedure was “detrimental” to perform in the presence of multiple risk factors, the investigator said.

By contrast, among patients treated with sunitinib alone, there was no significant difference in median overall survival for patients with one risk factor versus those with two or more risk factors, said Dr. Méjean, who is with the Hôpital Européen Georges-Pompidou and Paris Descartes University.

In another analysis of the data, delayed nephrectomy after initial systemic therapy was associated with long overall survival in good responders, supporting that approach as a “good therapeutic strategy,” he said.

Based on these results, Dr. Méjean told ASCO attendees he would “go back to the operating theater to operate just very selected patients.”

In a podium discussion, Alexander Kutikov, MD, FACS, said CARMENA makes it “undeniable” that up-front cytoreductive therapy should be applied to a “very select group” of patients.

While that select group may be defined as the one IMDC risk factor group, Dr. Kutkov said it is also appropriate to offer cytoreductive nephrectomy to carefully selected patients who do not need immediate systemic therapy.

“If the plan is to observe without systemic therapy, proceed with cytoreductive nephrectomy, and for everybody else, I think we take great caution in offering cytoreductive nephrectomy, because it absolutely can harm,” said Dr. Kutikov, professor and chief of urologic oncology at Fox Chase Cancer Center, Philadelphia.

The CARMENA update confirmed that, in general, cytoreductive nephrectomy should not be the standard of care, according to Dr. Méjean.

With follow-up of 61.5 months, or longer than what was previously reported for the 450-patient trial, cytoreductive nephrectomy followed by sunitinib was again found to be not superior to sunitinib alone, he said. Median overall survival was 15.6 months for the nephrectomy plus sunitinib arm versus 19.8 months for the sunitinib arm, showing that sunitinib alone was noninferior based on the statistical design of the trial (hazard ratio, 0.97; 95% CI, 0.79-1.19, with a fixed upper limit for noninferiority of 1.20).

Dr. Méjean reported disclosures related to Ipsen, Novartis, Pfizer, Bristol-Myers Squibb, Janssen, Sanofi and Roche.

SOURCE: Méjean A et al. ASCO 2019, Abstract 4508.

CHICAGO – While cytoreductive nephrectomy is generally still inadvisable in metastatic renal cell carcinoma patients who require medical therapy, an update of the CARMENA trial suggests the procedure may provide benefit for certain patients.

Patients with only one International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk factor may benefit from cytoreductive nephrectomy, said CARMENA investigator Arnaud Méjean, MD, PhD, in a presentation at the annual meeting of the American Society of Clinical Oncology.

Among patients in CARMENA treated with nephrectomy plus sunitinib, median overall survival was 31.4 months for those with just one risk factor, and 17.6 months for those with two or more (hazard ratio, 1.68; 95% confidence interval, 1.10-2.57; P = .01), suggesting the procedure was “detrimental” to perform in the presence of multiple risk factors, the investigator said.

By contrast, among patients treated with sunitinib alone, there was no significant difference in median overall survival for patients with one risk factor versus those with two or more risk factors, said Dr. Méjean, who is with the Hôpital Européen Georges-Pompidou and Paris Descartes University.

In another analysis of the data, delayed nephrectomy after initial systemic therapy was associated with long overall survival in good responders, supporting that approach as a “good therapeutic strategy,” he said.

Based on these results, Dr. Méjean told ASCO attendees he would “go back to the operating theater to operate just very selected patients.”

In a podium discussion, Alexander Kutikov, MD, FACS, said CARMENA makes it “undeniable” that up-front cytoreductive therapy should be applied to a “very select group” of patients.

While that select group may be defined as the one IMDC risk factor group, Dr. Kutkov said it is also appropriate to offer cytoreductive nephrectomy to carefully selected patients who do not need immediate systemic therapy.

“If the plan is to observe without systemic therapy, proceed with cytoreductive nephrectomy, and for everybody else, I think we take great caution in offering cytoreductive nephrectomy, because it absolutely can harm,” said Dr. Kutikov, professor and chief of urologic oncology at Fox Chase Cancer Center, Philadelphia.

The CARMENA update confirmed that, in general, cytoreductive nephrectomy should not be the standard of care, according to Dr. Méjean.

With follow-up of 61.5 months, or longer than what was previously reported for the 450-patient trial, cytoreductive nephrectomy followed by sunitinib was again found to be not superior to sunitinib alone, he said. Median overall survival was 15.6 months for the nephrectomy plus sunitinib arm versus 19.8 months for the sunitinib arm, showing that sunitinib alone was noninferior based on the statistical design of the trial (hazard ratio, 0.97; 95% CI, 0.79-1.19, with a fixed upper limit for noninferiority of 1.20).

Dr. Méjean reported disclosures related to Ipsen, Novartis, Pfizer, Bristol-Myers Squibb, Janssen, Sanofi and Roche.

SOURCE: Méjean A et al. ASCO 2019, Abstract 4508.

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 – 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 – In gastric and gastroesophageal junction (GEJ) cancers, positive for PD-L1, treatment with the PD-1 inhibitor pembrolizumab offered comparable survival with fewer side effects, according to results of a phase 3 randomized clinical trial.

The checkpoint inhibitor also demonstrated a clinically meaningful improvement in patients who had high levels of PD-L1 expression, with a 2-year survival rate of 39% versus 22% for patients receiving the standard chemotherapy, which consisted of a platinum and a fluoropyrimidine, according to Josep Tabernero, MD, PhD, lead author of the KEYNOTE-062 study.

By contrast, the study failed to demonstrate that pembrolizumab immunotherapy combined with that chemotherapy backbone was superior to chemotherapy alone on survival endpoints, said Dr. Tabernero, Head of the Medical Oncology Department at the Vall d’Hebron Barcelona University Hospital and Institute of Oncology, Spain.

“There are several factors we are evaluating,” Dr. Tabernero said here in a press conference at the annual meeting of the American Society of Clinical Oncology (ASCO). “We still have to do more studies to understand why, with this chemotherapy backbone, we don’t see a clear synergistic effect for superiority in overall survival.”

Nevertheless, these findings make pembrolizumab a “preferred treatment” for many patients, particularly in light of its “substantially improved safety profile” versus chemotherapy, said ASCO Senior Vice President and Chief Medical Officer Richard L. Schilsky, MD.

“What I take away from this study is that for patients with advanced gastric and gastroesophageal cancer, pembrolizumab should really in many cases replace chemotherapy as a first-line treatment for this population,” Dr. Schilsky said in a press conference. “It’s certainly not worse, and it may well be better.”

The KEYNOTE-062 study included 763 patients with HER2-negative, PD-L1-positive advanced gastric or GEJ cancers randomized to one of three arms: pembrolizumab alone for up to 35 cycles, pembrolizumab for up to 35 cycles plus chemotherapy, or placebo plus chemotherapy.

Pembrolizumab alone was not inferior compared to chemotherapy, with median overall survival rates of 10.5 and 11.1 months, respectively (HR, 0.91; 99.2% CI, 0.69-1.18), Dr. Tabernero reported.

Overall survival appeared to be prolonged in patients with high levels of PD-L1 expression, defined as a combined positive score (CPS) of 10 or greater. The median survival in that subgroup was 17.4 months for those receiving pembrolizumab, and just 10.8 months for chemotherapy. However, the design of the study precluded an analysis of statistical significance for this finding, according to Dr. Tabernero.

Looking at the overall study population, pembrolizumab plus chemotherapy did not improve survival versus chemotherapy alone, he added, reporting median overall survivals of 12.5 and 11.1 months, respectively (P = .046).

Subgroup analysis suggested that Asian patients derived particular benefit from pembrolizumab as compared to chemotherapy, though Dr. Tabernero cautioned against overinterpretation of the finding, saying that it could be due to biology, or could be a statistical anomaly.

Funding for the study came from Merck & Co., Inc. Dr. Tabernero reported disclosures related to Bayer, Boehringer Ingelheim, Lilly, MSD, Merck Serono, Novartis, Sanofi, and others.

SOURCE: Tabernero J, et al. ASCO 2019. Abstract LBA4007.

CHICAGO – In gastric and gastroesophageal junction (GEJ) cancers, positive for PD-L1, treatment with the PD-1 inhibitor pembrolizumab offered comparable survival with fewer side effects, according to results of a phase 3 randomized clinical trial.

The checkpoint inhibitor also demonstrated a clinically meaningful improvement in patients who had high levels of PD-L1 expression, with a 2-year survival rate of 39% versus 22% for patients receiving the standard chemotherapy, which consisted of a platinum and a fluoropyrimidine, according to Josep Tabernero, MD, PhD, lead author of the KEYNOTE-062 study.

By contrast, the study failed to demonstrate that pembrolizumab immunotherapy combined with that chemotherapy backbone was superior to chemotherapy alone on survival endpoints, said Dr. Tabernero, Head of the Medical Oncology Department at the Vall d’Hebron Barcelona University Hospital and Institute of Oncology, Spain.

“There are several factors we are evaluating,” Dr. Tabernero said here in a press conference at the annual meeting of the American Society of Clinical Oncology (ASCO). “We still have to do more studies to understand why, with this chemotherapy backbone, we don’t see a clear synergistic effect for superiority in overall survival.”

Nevertheless, these findings make pembrolizumab a “preferred treatment” for many patients, particularly in light of its “substantially improved safety profile” versus chemotherapy, said ASCO Senior Vice President and Chief Medical Officer Richard L. Schilsky, MD.

“What I take away from this study is that for patients with advanced gastric and gastroesophageal cancer, pembrolizumab should really in many cases replace chemotherapy as a first-line treatment for this population,” Dr. Schilsky said in a press conference. “It’s certainly not worse, and it may well be better.”

The KEYNOTE-062 study included 763 patients with HER2-negative, PD-L1-positive advanced gastric or GEJ cancers randomized to one of three arms: pembrolizumab alone for up to 35 cycles, pembrolizumab for up to 35 cycles plus chemotherapy, or placebo plus chemotherapy.

Pembrolizumab alone was not inferior compared to chemotherapy, with median overall survival rates of 10.5 and 11.1 months, respectively (HR, 0.91; 99.2% CI, 0.69-1.18), Dr. Tabernero reported.

Overall survival appeared to be prolonged in patients with high levels of PD-L1 expression, defined as a combined positive score (CPS) of 10 or greater. The median survival in that subgroup was 17.4 months for those receiving pembrolizumab, and just 10.8 months for chemotherapy. However, the design of the study precluded an analysis of statistical significance for this finding, according to Dr. Tabernero.

Looking at the overall study population, pembrolizumab plus chemotherapy did not improve survival versus chemotherapy alone, he added, reporting median overall survivals of 12.5 and 11.1 months, respectively (P = .046).

Subgroup analysis suggested that Asian patients derived particular benefit from pembrolizumab as compared to chemotherapy, though Dr. Tabernero cautioned against overinterpretation of the finding, saying that it could be due to biology, or could be a statistical anomaly.

Funding for the study came from Merck & Co., Inc. Dr. Tabernero reported disclosures related to Bayer, Boehringer Ingelheim, Lilly, MSD, Merck Serono, Novartis, Sanofi, and others.

SOURCE: Tabernero J, et al. ASCO 2019. Abstract LBA4007.

CHICAGO – In gastric and gastroesophageal junction (GEJ) cancers, positive for PD-L1, treatment with the PD-1 inhibitor pembrolizumab offered comparable survival with fewer side effects, according to results of a phase 3 randomized clinical trial.

The checkpoint inhibitor also demonstrated a clinically meaningful improvement in patients who had high levels of PD-L1 expression, with a 2-year survival rate of 39% versus 22% for patients receiving the standard chemotherapy, which consisted of a platinum and a fluoropyrimidine, according to Josep Tabernero, MD, PhD, lead author of the KEYNOTE-062 study.

By contrast, the study failed to demonstrate that pembrolizumab immunotherapy combined with that chemotherapy backbone was superior to chemotherapy alone on survival endpoints, said Dr. Tabernero, Head of the Medical Oncology Department at the Vall d’Hebron Barcelona University Hospital and Institute of Oncology, Spain.

“There are several factors we are evaluating,” Dr. Tabernero said here in a press conference at the annual meeting of the American Society of Clinical Oncology (ASCO). “We still have to do more studies to understand why, with this chemotherapy backbone, we don’t see a clear synergistic effect for superiority in overall survival.”

Nevertheless, these findings make pembrolizumab a “preferred treatment” for many patients, particularly in light of its “substantially improved safety profile” versus chemotherapy, said ASCO Senior Vice President and Chief Medical Officer Richard L. Schilsky, MD.

“What I take away from this study is that for patients with advanced gastric and gastroesophageal cancer, pembrolizumab should really in many cases replace chemotherapy as a first-line treatment for this population,” Dr. Schilsky said in a press conference. “It’s certainly not worse, and it may well be better.”

The KEYNOTE-062 study included 763 patients with HER2-negative, PD-L1-positive advanced gastric or GEJ cancers randomized to one of three arms: pembrolizumab alone for up to 35 cycles, pembrolizumab for up to 35 cycles plus chemotherapy, or placebo plus chemotherapy.

Pembrolizumab alone was not inferior compared to chemotherapy, with median overall survival rates of 10.5 and 11.1 months, respectively (HR, 0.91; 99.2% CI, 0.69-1.18), Dr. Tabernero reported.

Overall survival appeared to be prolonged in patients with high levels of PD-L1 expression, defined as a combined positive score (CPS) of 10 or greater. The median survival in that subgroup was 17.4 months for those receiving pembrolizumab, and just 10.8 months for chemotherapy. However, the design of the study precluded an analysis of statistical significance for this finding, according to Dr. Tabernero.

Looking at the overall study population, pembrolizumab plus chemotherapy did not improve survival versus chemotherapy alone, he added, reporting median overall survivals of 12.5 and 11.1 months, respectively (P = .046).

Subgroup analysis suggested that Asian patients derived particular benefit from pembrolizumab as compared to chemotherapy, though Dr. Tabernero cautioned against overinterpretation of the finding, saying that it could be due to biology, or could be a statistical anomaly.

Funding for the study came from Merck & Co., Inc. Dr. Tabernero reported disclosures related to Bayer, Boehringer Ingelheim, Lilly, MSD, Merck Serono, Novartis, Sanofi, and others.

SOURCE: Tabernero J, et al. ASCO 2019. Abstract LBA4007.

CHICAGO – While tyrosine kinase inhibitors (TKIs) have long dominated treatment approaches for EGFR-driven advanced non-small cell lung cancer, a few newer antibodies are showing early promise as potential new strategies to use after progression, recent reports show.

Both JNJ-372, an EGFR and MET bispecific antibody, and U3-1402, a HER3-directed antibody-drug conjugate (ADC), demonstrated manageable safety profiles and preliminary antitumor activity in phase 1 study results presented here at the annual meeting of the American Society of Clinical Oncology.

“There is definitely a role to play for antibodies in the TKI world,” said Jessica Ruth Bauman, MD, of Fox Chase Cancer Center, Philadelphia, Pa., a discussant on both abstracts.

These two antibodies harness new mechanisms of action that are not specific to a resistance mechanism, which may lead to broad applicability, according to Dr. Bauman.

“Mechanisms of acquired resistance have been the Achilles heel of EGFR TKI treatment,” she said.

The JNJ-372 bispecific antibody has preclinical data consistent with several proposed mechanisms of action, including inhibition of EGFR and cMet signaling, receptor degradation, and antibody-dependent cellular cytotoxicity, said investigator Eric B. Haura, MD, of H. Lee Moffitt Cancer Center & Research Institute, Tampa, Fla.

In the phase 1 study, which included patients with diverse EGFR mutations, 32 out of 108 patients (30%) had a best response of partial response (PR) after treatment with JNJ-372, Dr. Haura reported in an oral abstract presentation.

Responses were seen in patients with mutations that represent areas of high unmet need, including those with EGFR C797S-mediated or cMet-mediated resistance to the third-generation TKI osimertinib, and those with TKI-naïve EGFR exon 20 insertions, he emphasized in his presentation.

The safety profile was “manageable” and consistent with EGFR inhibition, he said, with a low (9%) rate of grade 3 or greater toxicities and frequent infusion-related reactions, mostly after the first dose.

Enrollment of patients with high unmet need is ongoing, according to Dr. Haura.

U3-1402, the antibody-drug conjugate that may have a place in the TKI world, consists of a fully human HER3-targeted antibody linked to a topoisomerase I inhibitor payload.

“Targeting HER3 with U3-1402 may be a practical approach to treat EGFR-mutant NSCLC with diverse mechanisms of resistance to EGFR TKIs,” said investigator Pasi A. Jänne, MD, PhD, of Dana-Farber Cancer Institute, Boston, Mass.

That’s because mechanisms of resistance to TKIs in EGFR-mutant NSCLC are turning out to be so diverse, that trying to combat each individual resistance mechanism is likely “impractical,” Dr. Jänne said.

Targeting HER3, the perhaps lesser-known of the four members of the EGFR tyrosine kinase family, may address multiple resistance mechanisms, and 57% to 67% of EGFR-mutant NSCLCs have at least some level of HER3 expression, according to the presenter.

In the phase 1 study data reported at the meeting, the response rate following U3-1402 treatment was about 31%, or 5 out of 16 patients, including 4 confirmed partial responses. Most treatment-emergent adverse events were grade 1 or 2, and only one patient discontinued due to an adverse event, according to Dr. Jänne, who said the study is ongoing.

Taken together, findings for U3-1402 and JNJ-372 show that there may be room for other approaches beyond TKIs to address the need for new therapies to overcome resistance, Dr. Bauman said in her commentary on these studies.

“Additional research will enable us to determine who will benefit from these compounds, what biomarkers are predictive, and novel combinations to consider,” she added.

Dr. Bauman reported a consulting or advisory role with Pfizer. Dr. Haura provided disclosures related to Bristol-Myers Squibb; Janssen Oncology, Boehringer Ingelheim, FORMA Therapeutics, Ignyta, Janssen, Lilly, and Ventana, plus a patent pending on technology related to kinase inhibitor sensitivity biomarkers. Dr. Jänne reported disclosures related to Gatekeeper Pharmaceuticals, Loxo, Araxes Pharma, AstraZeneca, Boehringer Ingelheim, Daiichi Sankyo, Lilly, and others.

SOURCE: Haura EB, et al. ASCO 2019. Abstract 9009, Jänne PA, et al. ASCO 2019. Abstract 9010.

CHICAGO – While tyrosine kinase inhibitors (TKIs) have long dominated treatment approaches for EGFR-driven advanced non-small cell lung cancer, a few newer antibodies are showing early promise as potential new strategies to use after progression, recent reports show.

Both JNJ-372, an EGFR and MET bispecific antibody, and U3-1402, a HER3-directed antibody-drug conjugate (ADC), demonstrated manageable safety profiles and preliminary antitumor activity in phase 1 study results presented here at the annual meeting of the American Society of Clinical Oncology.

“There is definitely a role to play for antibodies in the TKI world,” said Jessica Ruth Bauman, MD, of Fox Chase Cancer Center, Philadelphia, Pa., a discussant on both abstracts.

These two antibodies harness new mechanisms of action that are not specific to a resistance mechanism, which may lead to broad applicability, according to Dr. Bauman.

“Mechanisms of acquired resistance have been the Achilles heel of EGFR TKI treatment,” she said.

The JNJ-372 bispecific antibody has preclinical data consistent with several proposed mechanisms of action, including inhibition of EGFR and cMet signaling, receptor degradation, and antibody-dependent cellular cytotoxicity, said investigator Eric B. Haura, MD, of H. Lee Moffitt Cancer Center & Research Institute, Tampa, Fla.

In the phase 1 study, which included patients with diverse EGFR mutations, 32 out of 108 patients (30%) had a best response of partial response (PR) after treatment with JNJ-372, Dr. Haura reported in an oral abstract presentation.

Responses were seen in patients with mutations that represent areas of high unmet need, including those with EGFR C797S-mediated or cMet-mediated resistance to the third-generation TKI osimertinib, and those with TKI-naïve EGFR exon 20 insertions, he emphasized in his presentation.

The safety profile was “manageable” and consistent with EGFR inhibition, he said, with a low (9%) rate of grade 3 or greater toxicities and frequent infusion-related reactions, mostly after the first dose.

Enrollment of patients with high unmet need is ongoing, according to Dr. Haura.

U3-1402, the antibody-drug conjugate that may have a place in the TKI world, consists of a fully human HER3-targeted antibody linked to a topoisomerase I inhibitor payload.

“Targeting HER3 with U3-1402 may be a practical approach to treat EGFR-mutant NSCLC with diverse mechanisms of resistance to EGFR TKIs,” said investigator Pasi A. Jänne, MD, PhD, of Dana-Farber Cancer Institute, Boston, Mass.

That’s because mechanisms of resistance to TKIs in EGFR-mutant NSCLC are turning out to be so diverse, that trying to combat each individual resistance mechanism is likely “impractical,” Dr. Jänne said.

Targeting HER3, the perhaps lesser-known of the four members of the EGFR tyrosine kinase family, may address multiple resistance mechanisms, and 57% to 67% of EGFR-mutant NSCLCs have at least some level of HER3 expression, according to the presenter.

In the phase 1 study data reported at the meeting, the response rate following U3-1402 treatment was about 31%, or 5 out of 16 patients, including 4 confirmed partial responses. Most treatment-emergent adverse events were grade 1 or 2, and only one patient discontinued due to an adverse event, according to Dr. Jänne, who said the study is ongoing.

Taken together, findings for U3-1402 and JNJ-372 show that there may be room for other approaches beyond TKIs to address the need for new therapies to overcome resistance, Dr. Bauman said in her commentary on these studies.

“Additional research will enable us to determine who will benefit from these compounds, what biomarkers are predictive, and novel combinations to consider,” she added.

Dr. Bauman reported a consulting or advisory role with Pfizer. Dr. Haura provided disclosures related to Bristol-Myers Squibb; Janssen Oncology, Boehringer Ingelheim, FORMA Therapeutics, Ignyta, Janssen, Lilly, and Ventana, plus a patent pending on technology related to kinase inhibitor sensitivity biomarkers. Dr. Jänne reported disclosures related to Gatekeeper Pharmaceuticals, Loxo, Araxes Pharma, AstraZeneca, Boehringer Ingelheim, Daiichi Sankyo, Lilly, and others.

SOURCE: Haura EB, et al. ASCO 2019. Abstract 9009, Jänne PA, et al. ASCO 2019. Abstract 9010.

CHICAGO – While tyrosine kinase inhibitors (TKIs) have long dominated treatment approaches for EGFR-driven advanced non-small cell lung cancer, a few newer antibodies are showing early promise as potential new strategies to use after progression, recent reports show.

Both JNJ-372, an EGFR and MET bispecific antibody, and U3-1402, a HER3-directed antibody-drug conjugate (ADC), demonstrated manageable safety profiles and preliminary antitumor activity in phase 1 study results presented here at the annual meeting of the American Society of Clinical Oncology.

“There is definitely a role to play for antibodies in the TKI world,” said Jessica Ruth Bauman, MD, of Fox Chase Cancer Center, Philadelphia, Pa., a discussant on both abstracts.

These two antibodies harness new mechanisms of action that are not specific to a resistance mechanism, which may lead to broad applicability, according to Dr. Bauman.

“Mechanisms of acquired resistance have been the Achilles heel of EGFR TKI treatment,” she said.

The JNJ-372 bispecific antibody has preclinical data consistent with several proposed mechanisms of action, including inhibition of EGFR and cMet signaling, receptor degradation, and antibody-dependent cellular cytotoxicity, said investigator Eric B. Haura, MD, of H. Lee Moffitt Cancer Center & Research Institute, Tampa, Fla.

In the phase 1 study, which included patients with diverse EGFR mutations, 32 out of 108 patients (30%) had a best response of partial response (PR) after treatment with JNJ-372, Dr. Haura reported in an oral abstract presentation.

Responses were seen in patients with mutations that represent areas of high unmet need, including those with EGFR C797S-mediated or cMet-mediated resistance to the third-generation TKI osimertinib, and those with TKI-naïve EGFR exon 20 insertions, he emphasized in his presentation.

The safety profile was “manageable” and consistent with EGFR inhibition, he said, with a low (9%) rate of grade 3 or greater toxicities and frequent infusion-related reactions, mostly after the first dose.

Enrollment of patients with high unmet need is ongoing, according to Dr. Haura.

U3-1402, the antibody-drug conjugate that may have a place in the TKI world, consists of a fully human HER3-targeted antibody linked to a topoisomerase I inhibitor payload.

“Targeting HER3 with U3-1402 may be a practical approach to treat EGFR-mutant NSCLC with diverse mechanisms of resistance to EGFR TKIs,” said investigator Pasi A. Jänne, MD, PhD, of Dana-Farber Cancer Institute, Boston, Mass.

That’s because mechanisms of resistance to TKIs in EGFR-mutant NSCLC are turning out to be so diverse, that trying to combat each individual resistance mechanism is likely “impractical,” Dr. Jänne said.

Targeting HER3, the perhaps lesser-known of the four members of the EGFR tyrosine kinase family, may address multiple resistance mechanisms, and 57% to 67% of EGFR-mutant NSCLCs have at least some level of HER3 expression, according to the presenter.

In the phase 1 study data reported at the meeting, the response rate following U3-1402 treatment was about 31%, or 5 out of 16 patients, including 4 confirmed partial responses. Most treatment-emergent adverse events were grade 1 or 2, and only one patient discontinued due to an adverse event, according to Dr. Jänne, who said the study is ongoing.

Taken together, findings for U3-1402 and JNJ-372 show that there may be room for other approaches beyond TKIs to address the need for new therapies to overcome resistance, Dr. Bauman said in her commentary on these studies.

“Additional research will enable us to determine who will benefit from these compounds, what biomarkers are predictive, and novel combinations to consider,” she added.

Dr. Bauman reported a consulting or advisory role with Pfizer. Dr. Haura provided disclosures related to Bristol-Myers Squibb; Janssen Oncology, Boehringer Ingelheim, FORMA Therapeutics, Ignyta, Janssen, Lilly, and Ventana, plus a patent pending on technology related to kinase inhibitor sensitivity biomarkers. Dr. Jänne reported disclosures related to Gatekeeper Pharmaceuticals, Loxo, Araxes Pharma, AstraZeneca, Boehringer Ingelheim, Daiichi Sankyo, Lilly, and others.

SOURCE: Haura EB, et al. ASCO 2019. Abstract 9009, Jänne PA, et al. ASCO 2019. Abstract 9010.