The efficacy and safety of olaparib, an oral poly(ADP-ribose) polymerase (PARP) inhibitor, was investigated in a subgroup of patients with germline BRCA1/2 mutated (gBRCA1/2m) advanced ovarian cancer who had received ≥ 3 prior lines of chemotherapy. Primary data from this Phase II study (Study 42, ClinicalTrials.govNCT01078662) have been reported previously.

Eligible patients were treated with oral olaparib 400 mg bid capsule monotherapy until disease progression according to RECIST v1.1. Objective response rate (ORR) and duration of response (DoR) were assessed for patients with measurable disease at baseline. Safety and tolerability were assessed for all patients by adverse event (AE) incidence and changes in laboratory parameters. Platinum resistance status was obtained retrospectively, and responses to olaparib evaluated.

In patients with gBRCA1/2m ovarian cancer, 154/193 (80%) had received ≥ 3 prior lines of chemotherapy, of whom 137/154 (89%) had measurable disease at baseline. ORR was 34% (46/137; 95% confidence interval [CI] 26–42) and median DoR was 7.9 (95% CI 5.6–9.6) months. ORR in platinum-resistant tumors was 30%. Median DoR for platinum-sensitive and platinum-resistant disease was similar: 8.2 months (95% CI 5.6–13.5) compared with 8.0 months (4.8–14.8), respectively. Six of the 193 (3%) patients had an AE with an outcome of death. None of these AEs at time of occurrence was considered causally related to olaparib.

Following ≥ 3 prior lines of chemotherapy, olaparib 400 mg bid (capsule form) monotherapy demonstrated notable antitumor activity in patients with gBRCA1/2m advanced ovarian cancer. No new safety signals were identified.