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

Abstract

Background: The unmet need for effective and tolerable mPC treatments is high. PC pts with a germline BRCA1 and/or BRCA2 mutation (gBRCAm) have shown response tothePARP inhibitor olaparib (O; Kaufman 2015). POLO (NCT02184195), the first Phase III trial to evaluate the efficacy of maintenance PARP inhibitor treatment in PC, demonstrated a statistically significant and clinically meaningful improvement in progression-free survival (PFS) from maintenance O vs placebo (P) for pts with a gBRCAm and mPC whose disease had not progressed during PBC (median 7.4 vs 3.8 months; hazard ratio [HR] 0.53; 95% CI 0.35-0.82; P = 0.004). At 2 years, 22.1% of pts on O vs 9.6% of pts on P were progression free. At an interim overall survival analysis (46% maturity), the HR was 0.91 (95% CI 0.56-1.46; P = 0.68). Safety was consistent with the known profile for O (Golan 2019). Methods: POLO is a randomized, double-blind, placebo-controlled trial of pts with a gBRCAm and pancreatic adenocarcinoma who had received >16 weeks of first-line PBC for mPC without progression. There was no limit to duration of chemotherapy. Pts were randomized 3:2 to maintenance O tablets (300 mg bid) or P. Treatment began 4-8 weeks after the last PBC dose, continuing until investigator-assessed progression or unacceptable toxicity. The primary endpoint, PFS, and objective response were assessed by blinded independent central review (modified RECIST 1.1). Results: Objective response rate among pts with measurable disease at baseline was 23.1% (18/78) in the O and 11.5% (6/52) in the P arm (odds ratio 2.30; 95% CI 0.89-6.76;P =0.103). Conclusions: Pts with a gBRCAm and mPC whose disease had not progressed on PBC derived a statistically significant and clinically meaningful PFS benefit from maintenance O. O-arm pts were more likely to maintain disease control or achieve a response than P-arm pts, and responses were durable, lasting a median of more than 2 years.