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
Authors
Clamp, Andrew RLorusso, D.
Oza, A. M.
Aghajanian, C.
Oaknin, A.
Dean, A.
Colombo, N.
Weberpals, J. I.
Scambia, G.
Leary, A.
Holloway, R. W.
Amenedo Gancedo, M.
Fong, P. C.
Goh, J. C.
O'Malley, D. M.
Armstrong, D. K.
Banerjee, S.
García-Donas, J.
Swisher, E. M.
Cameron, T.
Goble, S.
Coleman, R. L
Ledermann, J. A.
Affiliation
Department of Medical Oncology, The Christie NHS Foundation Trust and University of Manchester, Manchester, UK.Issue Date
2021
Metadata
Show full item recordAbstract
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.Citation
Clamp AR, Lorusso D, Oza AM, Aghajanian C, Oaknin A, Dean A, et al. 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. Int J Gynecol Cancer . 2021 Jun 8;31(7):949–58.Journal
International Journal of Gynecologic CancerDOI
10.1136/ijgc-2020-002240PubMed ID
34103386Additional Links
https://dx.doi.org/10.1136/ijgc-2020-002240Type
ArticleLanguage
enae974a485f413a2113503eed53cd6c53
10.1136/ijgc-2020-002240
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