In the phase 3 study ARIEL3, rucaparib (600 mg BID) maintenance treatment following response to platinum-based chemotherapy significantly improved progression-free survival (PFS) vs placebo in all patient populations regardless of biomarker status (Coleman. Lancet. 2017;390:1949-61). This post hoc exploratory analysis investigated the effect of the number of prior chemotherapy regimens on investigator-assessed PFS, the primary endpoint in ARIEL3.
All patients received ≥2 prior platinum-based regimens per the protocol. Investigator-assessed PFS was evaluated in subgroups of patients who received 2 or ≥3 prior chemotherapy regimens and is reported by predefined cohort: BRCA mutant; BRCA mutant + BRCA wild type/high loss of heterozygosity (LOH); and intent-to-treat (ITT) population.
The visit cutoff dates for efficacy and safety were 15 April 2017 (date of unblinding for primary efficacy analyses) and 15 August 2017 (date of dataset in the US prescribing information).
In the BRCA-mutant cohort, median PFS in the 2 prior chemotherapies subgroup (rucaparib, n=73; placebo, n=40) was 21.9 vs 5.4 months (hazard ratio [HR], 0.24; 95% confidence interval [CI], 0.14-0.40; P<0.0001) and in the ≥3 prior chemotherapies subgroup (rucaparib, n=57; placebo, n=26) was 13.7 vs 5.4 months (HR, 0.21; 95% CI, 0.11-0.40; P<0.0001).
In the BRCA mutant + BRCA wild-type/high LOH cohort, median PFS in the 2 prior chemotherapies subgroup (rucaparib, n=136; placebo, n=75) was 14.1 vs 5.5 months (HR, 0.34; 95% CI, 0.23-0.49; P<0.0001) and in the ≥3 prior chemotherapies subgroup (rucaparib, n=100; placebo, n=43) was 11.1 vs 5.4 months (HR, 0.27; 95% CI, 0.16-0.44; P<0.0001).
In the ITT population, median PFS in the 2 prior chemotherapies subgroup (rucaparib, n=231; placebo, n=124) was 10.4 vs 5.4 months (HR, 0.42; 95% CI, 0.32-0.55; P<0.0001) and in the ≥3 prior chemotherapies subgroup (rucaparib, n=144; placebo, n=65) was 11.1 vs 5.3 months (HR, 0.28; 95% CI, 0.19-0.41; P<0.0001).
Rucaparib’s safety profile was consistent between the 2 and ≥3 prior chemotherapies subgroups as assessed by the rate of grade ≥3 (59% and 59%) treatment-emergent adverse events.
Rucaparib maintenance treatment improved PFS vs placebo in all predefined cohorts regardless of the number of prior chemotherapy regimens received.