Clinical and molecular characteristics of ARIEL3 patients who derived exceptional benefit from rucaparib maintenance treatment for high-grade ovarian cancer (HGOC).

Abstract

5537 Background: ARIEL3 is a placebo-controlled randomized trial of the PARP inhibitor (PARPi) rucaparib as maintenance treatment in HGOC patients (pts) who responded to the latest line of platinum therapy (NCT01968213). Rucaparib improved progression-free survival (PFS) across all predefined subgroups. Here, we present an exploratory analysis of clinical and molecular characteristics associated with exceptional benefit from rucaparib. Methods: Pts were randomized 2:1 to receive rucaparib 600 mg BID or placebo. At the data cutoff of Dec 31, 2019, 33/375 (9%) and 1/189 (0.5%) pts were still ongoing and receiving rucaparib or placebo, respectively. Molecular features (genomic alterations, BRCA1 promoter methylation) and baseline clinical characteristics were compared between pts who derived exceptional benefit (PFS ≥2 yrs), and those with disease progression on first scan (≈12 wks; the short-term [ST] subgroup) within each treatment arm. Results: Of 564 pts, 83 (15%) showed exceptional benefit: 79/375 (21%) in the rucaparib arm and 4/189 (2%) in the placebo arm. Within the rucaparib arm, exceptional benefit pts had more favorable clinical prognostic factors at baseline compared with the ST subgroup (Table). While BRCA mutations were enriched in the rucaparib exceptional benefit subgroup, 34/79 (43%) of these pts were BRCA wild type. Among other biomarkers, RAD51C/D mutations were associated with exceptional benefit; low genome-wide loss of heterozygosity was enriched within the ST subgroup; and high BRCA1 methylation was present at similar fractions. Trends were similar in the placebo arm (Table). Conclusions: Exceptional benefit in ARIEL3 was more common in, but not exclusive to, pts with favorable clinical characteristics and known mechanisms of PARPi sensitivity. Our results suggest that rucaparib can deliver exceptional benefit to a diverse set of HGOC pts. Clinical trial information: NCT01968213. [Table: see text]