TY - JOUR T1 - Rucaparib maintenance treatment for recurrent ovarian carcinoma: the effects of progression-free interval and prior therapies on efficacy and safety in the randomized phase III trial ARIEL3 JF - International Journal of Gynecologic Cancer JO - Int J Gynecol Cancer SP - 949 LP - 958 DO - 10.1136/ijgc-2020-002240 VL - 31 IS - 7 AU - Andrew R Clamp AU - Domenica Lorusso AU - Amit M Oza AU - Carol Aghajanian AU - Ana Oaknin AU - Andrew Dean AU - Nicoletta Colombo AU - Johanne I Weberpals AU - Giovanni Scambia AU - Alexandra Leary AU - Robert W Holloway AU - Margarita Amenedo Gancedo AU - Peter C Fong AU - Jeffrey C Goh AU - David M O’Malley AU - Deborah K Armstrong AU - Susana Banerjee AU - Jesus García-Donas AU - Elizabeth M Swisher AU - Terri Cameron AU - Sandra Goble AU - Robert L Coleman AU - Jonathan A Ledermann Y1 - 2021/07/01 UR - http://ijgc.bmj.com/content/31/7/949.abstract N2 - Introduction In ARIEL3 (NCT01968213), the poly(adenosine diphosphate-ribose) polymerase inhibitor rucaparib significantly improved progression-free survival versus placebo regardless of biomarker status when used as maintenance treatment for recurrent ovarian cancer. The aim of the current analyses was to evaluate the efficacy and safety of rucaparib in subgroups based on progression-free interval following penultimate platinum, number of prior chemotherapies, and prior use of bevacizumab.Methods Patients were randomized 2:1 to rucaparib 600 mg twice daily or placebo. Within subgroups, progression-free survival was assessed in prespecified, nested cohorts: BRCA-mutant, homologous recombination deficient (BRCA-mutant or wild-type BRCA/high genomic loss of heterozygosity), and the intent-to-treat population.Results In the intent-to-treat population, median investigator-assessed progression-free survival was 8.2 months with rucaparib versus 4.1 months with placebo (n=151 vs n=76; HR 0.33, 95% CI 0.24 to 0.46, p<0.0001) for patients with progression-free interval 6 to ≤12 months, and 13.6 versus 5.6 months (n=224 vs n=113; HR 0.39, 95% CI 0.30 to 0.52, p<0.0001) for those with progression-free interval >12 months. Median progression-free survival was 10.4 versus 5.4 months (n=231 vs n=124; HR 0.42, 95% CI 0.32 to 0.54, p<0.0001) for patients who had received two prior chemotherapies, and 11.1 versus 5.3 months (n=144 vs n=65; HR 0.28, 95% CI 0.19 to 0.41, p<0.0001) for those who had received ≥3 prior chemotherapies. Median progression-free survival was 10.3 versus 5.4 months (n=83 vs n=43; HR 0.42, 95% CI 0.26 to 0.68, p=0.0004) for patients who had received prior bevacizumab, and 10.9 versus 5.4 months (n=292 vs n=146; HR 0.35, 95% CI 0.28 to 0.45, p<0.0001) for those who had not. Across subgroups, median progression-free survival was also significantly longer with rucaparib versus placebo in the BRCA-mutant and homologous recombination deficient cohorts. Safety was consistent across subgroups.Conclusions Rucaparib maintenance treatment significantly improved progression-free survival versus placebo irrespective of progression-free interval following penultimate platinum, number of lines of prior chemotherapy, and previous use of bevacizumab.Requests for de-identified datasets for the results reported in this publication will be made available to qualified researchers following submission of a methodologically sound proposal to medinfo@clovisoncology.com. Data will be made available for such requests following online publication of this article and for 1 year thereafter in compliance with applicable privacy laws, data protection, and requirements for consent and anonymization. Data will be provided by Clovis Oncology. The redacted protocol for the ARIEL3 clinical study is available on ClinicalTrials.gov (NCT01968213). Clovis Oncology does not share identified participant data or a data dictionary. ER -