Objectives ARIEL3 is a placebo-controlled randomized trial of the PARP inhibitor (PARPi) rucaparib as maintenance treatment in HGOC patients 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 characteristics associated with exceptional benefit from rucaparib.
Methods Patients were randomized 2:1 to rucaparib 600 mg BID or placebo. As of 31 Dec 2019 (data cutoff), 33/375 (9%) and 1/189 (0.5%) patients were still ongoing and receiving rucaparib or placebo. Molecular features (genomic alterations, BRCA1 promoter methylation) and baseline clinical characteristics were compared between patients who derived exceptional benefit (PFS ≥2 yrs), and those with disease progression on first scan (≈12 wks; the short-term subgroup) within each treatment arm.
Results of 564 patients, 79/375 (21%) in the rucaparib arm and 4/189 (2%) in the placebo arm showed exceptional benefit. Within the rucaparib arm, exceptional benefit patients had more favorable clinical prognostic factors at baseline versus the short-term subgroup (Table). Although BRCA mutations were enriched in the rucaparib exceptional benefit subgroup, 33/79 (42%) of these patients were BRCA wild type. Patterns of enrichment varied among other biomarkers. Overall trends were similar in the placebo arm.
Conclusions Exceptional benefit in ARIEL3 was more common in, but not exclusive to, patients with favorable clinical characteristics and known mechanisms of PARPi sensitivity. Our results suggest rucaparib can deliver exceptional benefit to a diverse set of patients with HGOC.
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