Population exposure-efficacy and exposure-safety analyses for rucaparib in patients with recurrent ovarian carcinoma from Study 10 and ARIEL2.

To evaluate correlations between rucaparib exposure and selected efficacy and safety endpoints in patients with recurrent ovarian carcinoma using pooled data from Study 10 and ARIEL2. Efficacy analyses were limited to patients with carcinomas harboring a deleterious BRCA1 or BRCA2 mutation who had received ≥2 prior lines of chemotherapy. Safety was evaluated in all patients who received ≥1 rucaparib dose. Steady-state daily area under the concentration-time curve (AUC Rucaparib exposure was dose-proportional and not associated with baseline patient weight. In the exposure-efficacy analyses (n = 121), AUC The exposure-response analyses provide support for the approved starting dose of rucaparib 600 mg BID for maximum clinical benefit with subsequent dose modification only following the occurrence of a treatment-emergent adverse event in patients with BRCA-mutated recurrent ovarian carcinoma.

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Copyright © 2021. Published by Elsevier Inc.

Déclaration de conflit d'intérêts

Declaration of competing interest G.E. Konecny has served on speaker bureaus for Clovis Oncology, GSK and AstraZeneca and received research funding from Lilly and Merck. A.M. Oza reports grants from AstraZeneca; has served on steering committee for Clovis Oncology; and has served as a principal investigator of an investigator initiated clinical trial from GSK. A.V. Tinker received grants and honoraria from AstraZeneca. A. Oaknin reports grants from Clovis Oncology, Abbie Deutchland, Ability Pharma, Advaxis, Aeterna Zentaris, Amgen SA, Aprea Therapeutics AB, BMS, Bristrol Meyers Squibb, Eisai, F. Hoffmann - La Roche Ltd., Regeneron Pharmaceuticals, Immunogen, Merck Sharp & Dohme de España SA, Millennium Pharmaceutials, PharmaMar, and Tesaro; received personal fees from Clovis Oncology, AstraZeneca, Deciphera Pharmarceutial, Genmab, GSK, Immunogen, Mersana Therapeutic, Pharma Mar, Roche, and Tesaro; and received support for travel or accommodation from Clovis Oncology, AstraZeneca, PharmaMar, and Roche. R. Shapira-Frommer has no conflicts to report. I. Ray-Coquard has reports grants from BMS, GSK, and Roche; received personal fees from Clovis Oncology, AstraZeneca, BMS, Deciphera Pharmaceuticals, GSK, and Roche; and received support for travel from AstraZeneca. C. Aghajanian has served on steering committees for AbbVie and Genentech; has served on advisory boards for and received honoraria from Clovis Oncology, AbbVie, AstraZeneca, AstraZeneca/Merck, Eisai/Merck, Immunogen, Mersana Therapeutics, Roche/Genentech, and Tesaro; has served as a National Coordinating Investigator to AstraZeneca; and reports grants from Clovis Oncology, AbbVie, AstraZeneca, and Genentech. R.L. Coleman reports grants from Clovis Oncology, AstraZeneca, Genmab, Janssen, Merck, and Roche/Genentech; and has served as a consultant to Clovis Oncology, Agenus, AstraZeneca, Genmab, GSK, Janssen, OncoQuest, Regeneron Pharmaceuticals, and Roche/Genentech. D.M. O'Malley reports grants, personal fees, and other from Clovis during the conduct of the study; has served on advisory boards for Agenus, AstraZeneca, Eisai, Genentech/Roche, Immunogen, Iovance Biotherapeutics, Janssen/Johnson & Johnson, Merck, Mersana, Myriad, Novartis Pharmaceuticals, Novocure, Regeneron Pharmaceuticals, SeaGen, Tarveda, and Tesaro/GSK; has served on steering committees for Amgen; has served as a consultant to AbbVie, Agenus, Ambry, AstraZeneca, Eisai, Genentech/Roche, GOG Foundation, Immunogen, Iovance Biotherapeutics, Merck, Mersana, Novartis Pharmaceuticals, Novocure, Seagen, and Tesaro/GSK; and his institution has received research support from AbbVie, Agenus, Ajinomoto, Amgen, Array BioPharma, AstraZeneca, Bristol-Myers Squibb, Cerulean Pharma, Eisai, EMD Serono, Ergomed Clinical Research, Genmab, Genentech/Roche, GOG Foundation, ImmunoGen, INC Research, inVentiv Health Clinical, Iovance Biotherapeutics, Janssen/Johnson & Johnson, Ludwig Institute for Cancer Research, Merck, Mersana, New Mexico Cancer Care Alliance, Novocure, PRA International, Regeneron Pharmaceuticals, Seagen, Serono, Stemcentrx, Tesaro/GSK, TRACON Pharmaceuticals, VentiRx, and Yale University. A. Leary reports grants from Clovis Oncology, Ability Pharma, Agenus, AstraZeneca, GSK, Inivata, Iovance Biotherapeutics, MSD, Roche, Sanofi, and Tesaro; and received personal fees from Clovis Oncology, Ability Pharma, AstraZeneca, Biocad, GSK, MSD, Tesaro, and Zentalis. L.m. Chen has no conflicts to report. D. Provencher has served on advisory boards for Clovis Oncology, AstraZeneca, GlaxoSmithKline, Roche-Genentech, and Tesaro. L. Ma has no conflicts to report. J.D. Brenton has served as a leader to Tailor Bio; owns stock and other ownership interests in Inivata Ltd. and Tailor Bio; has received honoraria from GSK; has served as a consultant or on advisory boards for AstraZeneca; his institution has received research funding from Aprea; has patents, royalties, other intellectual property for TAm-Seq v2 method for ctDNA estimation and for enhanced detection of target DNA by fragment size analysis; and received support for travel, accommodation, and expenses from GSK. C. Castro received personal fees from Qiagen. M. Green is an employee of Certara and was a paid contractor to Clovis Oncology in connection with the analysis and development of this manuscript. A. D. Simmons, J. Beltman, T. Harding, K. K. Lin, S. Goble, L. Maloney, and J.J. Xiao are employees of Clovis Oncology and may own stock or have stock options in that company. R.S. Kristeleit reports grants from MSD; reports personal fees from Clovis Oncology, Eisai, GSK, MSD, and Roche; and received non-financial support from GSK. I.A. McNeish has served on advisory boards for Clovis Oncology. E.M. Swisher has no conflicts to report.