On December 27, 2019, the FDA accelerated the approval of a new indication for olaparib (Lynparza; AstraZeneca) for the maintenance treatment of adults with metastatic pancreatic adenocarcinoma associated with a deleterious or suspected deleterious germline BRCA mutation, as detected by an FDA-approved test, and whose disease did not progress during ≥16 weeks of a first-line platinum-based chemotherapy regimen. Olaparib has been previously approved for ovarian cancer and for breast cancer associated with BRAF mutation.
At the same time, the FDA approved the BRACAnalysis CDx test (Myriad Genetic Laboratories) as a companion diagnostic for the selection of patients with pancreatic cancer for treatment with olaparib based on the identification of deleterious or suspected deleterious germline BRCA1 or BRCA2 mutations.
This approval was based on results from the POLO clinical trial, a double-blind, placebo-controlled, multicenter study that randomized (3:2) 154 patients with metastatic pancreatic adenocarcinoma associated with a deleterious or suspected deleterious germline BRCA mutation to olaparib 300 mg orally twice daily or to placebo until disease progression or unacceptable toxicity.
The main efficacy measure was progression-free survival (PFS). Additional outcome measures included overall survival (OS) and overall response rate (ORR). The median PFS was 7.4 months (95% confidence interval [CI], 4.1-11) with olaparib compared with 3.8 months (95% CI, 3.5-4.9) with placebo (hazard ratio [HR], 0.53; 95% CI, 0.35-0.81; P = .0035). The median OS was 18.9 months (95% CI, 14.9-26.2) with olaparib versus 18.1 months (95% CI, 12.6-26.1) with placebo (HR, 0.91; 95% CI, 0.56-1.46; P = .683); the ORRs in patients with measurable disease at baseline were 23% versus 12%, respectively.
The adverse reactions with olaparib in the POLO study were consistent with the safety profile of olaparib.