Subgroup analysis of rucaparib in platinum-sensitive recurrent ovarian carcinoma: Effect of prior chemotherapy regimens in ARIEL3

Abstract

Background: In the randomised, placebo‐controlled, phase 3 study ARIEL3, patients were randomised 2:1 to oral rucaparib (600 mg BID) or placebo as maintenance treatment following response to platinum‐based chemotherapy. Rucaparib significantly improved progression‐free survival (PFS) vs placebo in all patient populations regardless of biomarker status (Coleman et al. Lancet. 2017;390:1949‐61). This post hoc exploratory analysis investigated the effect of the number of prior chemotherapy regimens on the primary and secondary endpoints of investigator‐assessed and blinded independent central review (BICR)‐assessed PFS in ARIEL3. Methods: In ARIEL3, all patients received≥2 prior platinum‐based regimens in accordance with the protocol. PFS was explored in subgroups of patients who received 2 or≥3 prior chemotherapy regimens. These subgroup analyses were presented for the following predefined cohorts: BRCA mutant; BRCA mutant or BRCA wild type/high loss of heterozygosity (LOH); and intent‐to‐treat (ITT) population (ie, all randomised patients). Results: The visit cutoff dates for efficacy and safety were 15 April 2017 and 15 August 2017, respectively. In each predefined cohort, rucaparib significantly improved PFS compared to placebo irrespective of the number of prior chemotherapy regimens (ie, 2 or≥3) (Table). Rucaparib's safety profile was consistent between patients who received 2 or≥3 prior chemotherapy regimens as assessed by the rate of all grade (100% and 100%) and grade ≥3 (59% and 59%) treatment‐emergent adverse events (TEAEs) and dose modifications (ie, treatment interruptions and/or dose reductions due to a TEAE) (70% and 74%) in each respective subgroup. Conclusions: Maintenance treatment with rucaparib improved PFS vs placebo in all 3 predefined cohorts regardless of the number of prior chemotherapy regimens received.