POLO: maintenance olaparib for germline BRCA-mutated metastatic pancreatic cancer
In patients with inherited BRCA mutations whose pancreatic cancer had been held in check by platinum chemotherapy, switching to the tablet olaparib roughly doubled the time before the disease grew again compared with placebo. It was the first biomarker-driven approval in pancreatic cancer.
Overview
International double-blind randomised phase 3 trial in 154 patients with a germline BRCA1 or BRCA2 mutation and metastatic pancreatic adenocarcinoma that had not progressed during at least 16 weeks of first-line platinum-based chemotherapy, randomised 3:2 to maintenance olaparib 300 mg twice daily or placebo.
Median progression-free survival was 7.4 months with olaparib and 3.8 months with placebo (hazard ratio 0.53); at the interim analysis there was no difference in overall survival. Health-related quality of life was maintained. The FDA approved olaparib for this indication in December 2019.
- Median progression-free survival 7.4 versus 3.8 months, hazard ratio 0.53.
- No overall survival difference at the interim analysis (hazard ratio about 0.9).
- About 4 to 7 percent of pancreatic cancers carry a germline BRCA mutation, so germline testing is needed to find candidates.
Germline testing for every pancreatic cancer patient, platinum first line for BRCA carriers, and olaparib maintenance for those who respond are all downstream of POLO.
- The final analysis found no significant overall survival benefit.
- Only 154 of over 3,300 screened patients were randomised; the trial required platinum sensitivity and excluded those who had progressed.
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