Maintenance olaparib extends PFS in pancreatic cancer with BRCA mutation

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.