Introduction/Background*ARIEL3 is a placebo-controlled randomized trial of the PARP inhibitor rucaparib as maintenance treatment in high-grade ovarian cancer (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.
Methodology Between 7 April 2014, and 19 July 2016, 564 patients were randomized 2:1 to rucaparib 600 mg BID or placebo. As of 31 December 2019 (data cutoff), 33/375 (9%) and 1/189 (0.5%) patients were still ongoing and receiving rucaparib or placebo. Molecular features (genomic alterations and BRCA1 promoter methylation) and baseline clinical characteristics were compared between patients who derived exceptional benefit (PFS ≥2 years), and those with disease progression on first scan (≈12 weeks; the short-term subgroup) within each treatment arm.
Result(s)*Of 564 patients, a greater percentage of rucaparib vs placebo patients showed exceptional benefit: 79/375 (21%) in the rucaparib arm and 4/189 (2%) in the placebo arm (including 26/375 [7%] patients in the rucaparib arm and 1/189 [0.5%] patient in the placebo arm with PFS >4 years as of the data cutoff date). Within the rucaparib arm, exceptional benefit patients had more favourable clinical prognostic factors at baseline versus the short-term subgroup (table 1). Although BRCA (BRCA1 or BRCA2) 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.
Conclusion*Exceptional benefit in ARIEL3 was more common in, but not exclusive to, patients with favourable clinical characteristics and known mechanisms of sensitivity to a PARP inhibitor. Our results suggest rucaparib can deliver exceptional benefit to a diverse set of patients with HGOC.
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