ASCO 2019 — Olaparib delays progression in BRCA+ pancreatic cancer


  • Debra Gordon
  • Oncology Conference reports
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Takeaway

  • Frontline maintenance olaparib significantly delayed progression vs placebo in germline BRCA+ metastatic pancreatic cancer, according to data from the phase 3 POLO trial.
  • Results should be practice-changing, experts said.

Why this matters

  • 5-year survival in metastatic pancreatic cancer is ~3%.
  • 4%-7% of pancreatic cancers have mutations in 1 or both BRCA genes.
  • Olaparib is a poly ADP ribose polymerase inhibitor with approved indications in breast and ovarian cancer. 

Study design

  • International, double-blind trial of 154 patients with BRCA+ pancreatic cancer who had received ≥16 weeks of first-line platinum-based chemotherapy.
  • Patients were randomly assigned 3:2 to olaparib (n=92) or placebo (n=62), continuing until progression or unacceptable toxicity.

Key findings

  • Olaparib reduced the risk for disease progression or death by 47% vs placebo (HR, 0.53; P=.0038).
  • Median PFS for patients was higher with olaparib (7.4 vs 3.8 months), regardless of response to prior treatment.
  • From 6 months onward, twice as many patients in the olaparib group remained progression-free vs placebo.
  • Grade ≥3 adverse events: olaparib, 40%; placebo, 23%.
  • Discontinuation: olaparib, 5.5%; placebo, 1.7%. 
  • Duration of response: olaparib, 24.9 months; placebo, 3.7 months.
  • Funding: AstraZeneca; Merck & Co., Inc., Kenilworth, NJ, USA.

Expert commentary

  • "This is a really huge step forward for patients with metastatic pancreatic cancer," said ASCO pancreatic cancer expert Suzanne Cole, MD, from the University of Texas Southwestern Medical Center in Dallas. "It is our duty to search for this genetic mutation in all patients with metastatic pancreatic cancer to identify those with the BRCA mutation who can benefit from an oral agent [and] can extend their life."