The following article features coverage from the American Society of Clinical Oncology 2019 meeting. Click here to read more of Cancer Therapy Advisor‘s conference coverage.

Maintenance therapy with the PARP inhibitor olaparib may significantly delay the progression of metastatic pancreatic cancer in patients with BRCA gene mutations, according to the results of a randomized, phase 3 trial presented at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, Illinois.1

Previous research has found 22% response rates in patients with pancreatic cancers with BRCA1/2 gene mutations who were treated with olaparib, following chemotherapy with gemcitabine.2 In the new study, researchers set out to see whether olaparib could delay disease progression after at least 16 weeks of initial platinum-based chemotherapy.

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The investigators randomly assigned 154 patients with pancreatic cancer who had germline BRCA mutations, in a 3:2 ratio, to receive olaparib (92 patients) or placebo (62 patients). Treatment was initiated between 4 and 8 weeks after a patient received their last dose of platinum-based chemotherapy. Median treatment duration was 6 months for patients who received olaparib and 3.7 months for those who received placebo.

At 6, 12, 18, and 24 months following randomization, the researchers found that patients who received olaparib were at least twice as likely to have no disease progression than those who received placebo.

Median progression-free survival was 7.4 months among patients who received olaparib compared with 3.8 months among patients who received placebo. In other words, olaparib decreased the risk of disease progression or death by 47% in those who received olaparib compared with those who received placebo.

The objective response rate in patients with measurable disease by blinded independent central review was 23.1%. Two patients in the olaparib arm had a complete response, and both complete responses were ongoing at data cutoff.

Lead study author Hedy Lee Kindler, MD, a professor of medicine at the University of Chicago Medical Center in Illinois, noted in a press briefing that median time to onset of response “was earlier in the placebo arm, suggesting that these responses were a carryover from first-line platinum-based chemotherapy.”

At one year following randomization, 33.7% of patients who were in the olaparib group were free of disease progression compared with 14.5% in the placebo group. At 2 years, 22.1% of people in the olaparib group were free of progression compared with 9.6% of patients in the placebo group.

Grade 3 or higher adverse events were found in 40% of patients who received olaparib compared with 23% of patients who received placebo. Moreover, 5.5% of patients who took olaparib discontinued treatment due to its toxicity compared with 1.7% of patients who received placebo.

The findings may warrant a new standard of care for patients with pancreatic cancer and BRCA mutations, said Dr Kindler. “What is truly remarkable is that the median duration of response to olaparib in these patients with metastatic pancreatic cancer was more than 2 years.”

“Our results are the first from a phase 3 trial to validate a targeted treatment in a biomarker-selected population of pancreatic cancer patients,” Dr Kindler said. She stressed in a post-plenary session the importance of offering germline testing to patients with newly diagnosed pancreatic cancer upfront — at diagnosis. If the test turns out to be positive, she said, the patient should be referred to a genetic counselor for guidance.

Read more of Cancer Therapy Advisor‘s coverage of ASCO’s annual meeting by visiting the conference page.

References

  1. Kindler H, Hammel P, Reni M, et al. Olaparib as maintenance treatment following first-line platinum-based chemotherapy (PBC) in patients (pts) with a germline BRCA mutation and metastatic pancreatic cancer (mPC): Phase III POLO trial. J Clin Oncol. 2019:37, (suppl; abstr LBA4). Presented at: 2019 American Society of Clinical Oncology (ASCO) Annual Meeting; May 31-June 4, 2019; Chicago, IL. Abstract LBA4.
  2. Kaufman B, Shapira-Frommer R, et al. Olaparib monotherapy in patients with advanced cancer and a germline BRCA1/2 mutation. J Clin Oncol. 2015;33(3):244-250.