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Clinical and molecular characteristics of ARIEL3 patients who derived exceptional benefit from rucaparib maintenance treatment for high-grade ovarian carcinoma

O'Malley, David M; Oza, Amit M; Lorusso, Domenica; Aghajanian, Carol; Oaknin, Ana; Dean, Andrew; Colombo, Nicoletta; ... Coleman, Robert L; + view all (2022) Clinical and molecular characteristics of ARIEL3 patients who derived exceptional benefit from rucaparib maintenance treatment for high-grade ovarian carcinoma. Gynecologic Oncology , 167 (3) pp. 404-413. 10.1016/j.ygyno.2022.08.021. Green open access

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Abstract

OBJECTIVE: ARIEL3 (NCT01968213) is a placebo-controlled randomized trial of the poly(ADP-ribose) polymerase inhibitor rucaparib as maintenance treatment in patients with recurrent high-grade ovarian carcinoma who responded to their latest line of platinum therapy. Rucaparib improved progression-free survival across all predefined subgroups. Here, we present an exploratory analysis of clinical and molecular characteristics associated with exceptional benefit from rucaparib. METHODS: Patients were randomized 2:1 to receive rucaparib 600 mg twice daily or placebo. Molecular features (genomic alterations, BRCA1 promoter methylation) and baseline clinical characteristics were evaluated for association with exceptional benefit (progression-free survival ≥2 years) versus progression on first scan (short-term subgroup) and other efficacy outcomes. RESULTS: Rucaparib treatment was significantly associated with exceptional benefit compared with placebo: 79/375 (21.1%) vs 4/189 (2.1%), respectively (p < 0.0001). Exceptional benefit was more frequent among patients with favorable baseline clinical characteristics and with carcinomas harboring molecular evidence of homologous recombination deficiency (HRD). A comparison between patients who derived exceptional benefit from rucaparib and those in the short-term subgroup revealed both clinical markers (no measurable disease at baseline, complete response to latest platinum, longer penultimate platinum-free interval) and molecular markers (BRCA1, BRCA2, RAD51C, and RAD51D alterations and genome-wide loss of heterozygosity) significantly associated with exceptional benefit. CONCLUSIONS: Exceptional benefit in ARIEL3 was more common in, but not exclusive to, patients with favorable clinical characteristics or molecular features associated with HRD. Our results suggest that rucaparib can deliver exceptional benefit to a diverse set of patients with recurrent high-grade ovarian carcinoma.

Type: Article
Title: Clinical and molecular characteristics of ARIEL3 patients who derived exceptional benefit from rucaparib maintenance treatment for high-grade ovarian carcinoma
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.ygyno.2022.08.021
Publisher version: https://doi.org/10.1016/j.ygyno.2022.08.021
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher's terms and conditions.
Keywords: Ovarian carcinoma, Genomics, Rucaparib, Safety
UCL classification: UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Oncology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
URI: https://discovery.ucl.ac.uk/id/eprint/10158397
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