Effect of response to last platinum-based chemotherapy in patients (pts) with platinum-sensitive, recurrent ovarian carcinoma in the phase III study ARIEL3 of rucaparib maintenance treatment

Abstract

Background: In ARIEL3, rucaparib maintenance treatment significantly improved progression-free survival (PFS) vs placebo and was associated with reductions in tumour burden in pts with measurable disease (Coleman et al. Lancet. 2017;390:1949- 61). This exploratory analysis evaluated the efficacy of rucaparib in ARIEL3 pts based on their best response to last platinum-based chemotherapy prior to enrolment. Methods: Pts were randomised 2:1 to oral rucaparib (600 mg BID) or placebo. Subgroup analysis was based on a randomisation stratification factor of best response to last platinum-based chemotherapy: complete response (CR) or partial response (PR). PFS was assessed in 3 predefined nested cohorts: BRCA mutant, BRCA mutant + BRCA wild type/high loss of heterozygosity (LOH), and the intent-to-treat (ITT) population. Response was also assessed for pts with nonmeasurable disease (eg, lesions <10mm) at baseline. For PFS and response, tumours were assessed per RECIST v1.1. Results: The visit cutoff dates for efficacy and safety were 15 Apr 2017 and 31 Dec 2017. Rucaparib significantly improved PFS vs placebo in the CR and PR subgroups, with a similar treatment effect in both subgroups across all cohorts (Table). Of pts with nonmeasurable disease at baseline, 23/104 (22.1%) rucaparib pts and 2/56 (3.6%) placebo pts had a CR, including 7 rucaparib pts without a BRCA mutation or high LOH. The most common grade ≥3 treatment-emergent adverse event (rucaparib vs placebo) was anaemia/decreased haemoglobin (CR subgroup, 24.0% vs 0%; PR subgroup, 20.2% vs 0.8%). Conclusions: Regardless of response to last platinum-based chemotherapy, rucaparib maintenance treatment significantly improved PFS vs placebo across all cohorts. Similar to pts with measurable disease at baseline, CRs were observed in rucaparibtreated pts with nonmeasurable disease. Safety was consistent across the CR and PR subgroups. (Table Presented).