Efficacy of maintenance olaparib plus bevacizumab according to clinical risk in patients with newly diagnosed, advanced ovarian cancer in the phase III PAOLA-1/ENGOT-ov25 trial.

Adding maintenance olaparib to bevacizumab provided a significant progression-free survival (PFS) benefit in patients with newly diagnosed, advanced ovarian cancer in the randomized, double-blind PAOLA-1/ENGOT-ov25 trial (NCT02477644). We analyzed PFS by clinical risk and biomarker status. Patients received olaparib 300 mg twice daily for up to 24 months plus bevacizumab 15 mg/kg every 3 weeks for up to 15 months in total, or placebo plus bevacizumab. This post hoc exploratory analysis evaluated PFS in patients classified as higher risk (stage III with upfront surgery and residual disease or neoadjuvant chemotherapy; stage IV) or lower risk (stage III with upfront surgery and no residual disease), and by biomarker status. Of 806 randomized patients, 74% were higher risk and 26% were lower risk. After a median 22.9 months of follow-up, PFS favored olaparib plus bevacizumab versus placebo plus bevacizumab in higher-risk patients (hazard ratio [HR] 0.60; 95% confidence interval [CI] 0.49-0.74) and lower-risk patients (0.46; 0.30-0.72). Olaparib plus bevacizumab provided a substantial PFS benefit versus bevacizumab alone in the homologous recombination deficiency (HRD)-positive subgroup (higher risk: HR 0.39; 95% CI 0.28-0.54 and lower risk: 0.15; 0.07-0.30), with 24-month PFS rates in lower-risk patients of 90% versus 43%, respectively (Kaplan-Meier estimates). In PAOLA-1, maintenance olaparib plus bevacizumab provided a substantial PFS benefit in HRD-positive patients with a reduction of risk of progression or death of 61% in the higher-risk group and of 85% in the lower-risk group compared with bevacizumab alone.

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Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of Competing Interest Philipp Harter reports grant support from AstraZeneca, Roche, GlaxoSmithKline, Boehringer Ingelheim, Medac, and Genmab; and consulting fees from Amgen, AstraZeneca, Roche, Tesaro, GlaxoSmithKline, Sotio, Zai Lab, Merck Sharp & Dohme, Clovis Oncology, and Immunogen. Marie Ange Mouret-Reynier has nothing to disclose. Sandro Pignata reports honoraria from AstraZeneca, Roche, Merck Sharp & Dohme, Pfizer, Tesaro, Clovis Oncology and PharmaMar. Claire Cropet has nothing to disclose. Antonio González-Martín reports grants from Roche and GSK (funding for ENGOT ov-41 trial and ANITA); consulting fees from Alkermes, Amgen, AstraZeneca, Clovis Oncology, GSK, Genmab, Mersana, Roche, Immunogen, MSD, Oncoinvent, PharmaMar, Sotio, and Takeda; honoraria from AstraZeneca, Clovis Oncology, GSK, Roche, and MSD; support for attending meetings and/or travel from AstraZeneca, GSK, Roche, MSD and PharmaMar; and being the Chairman of GEICO and Chairman of ENGOT (2018–2020). Gerhard Bogner reports advisory board fees from AstraZeneca and Roche. Keiichi Fujiwara reports consulting fees and grant support from Pfizer, Eisai, Merck Sharp & Dohme, Taiho, Zeria, Chugai Pharmaceutical, Genmab and Takeda Pharmaceutical Company, receiving grant support from Immunogen, Oncotherapy and Regeneron, and receiving consulting fees from Novartis, Kyowa Hakko Kirin, Daiichi Sankyo, Mochida Pharmaceutical and NanoCarrier. Ignace Vergote reports grant support from Amgen and Roche; research support from Oncoinvent AS and Genmab; consulting fees from Aksebio, Amgen (Europe) GmbH, AstraZeneca, Bristol Myers Squibb, Carrick Therapeutics, Clovis Oncology, Deciphera Pharmaceuticals, Eisai, Elevar Therapeutics, F. Hoffman-La Roche Ltd., Genmab, GSK, Immunogen Inc., Jazz Pharma, Karyopharm, Mersana, Millennium Pharmaceuticals, MSD, Novocure, Novartis, Octimet Oncology NV, Oncoinvent AZ, Seagen, Sotio a.s., Verastem Oncology, Zentalis; and support for attending meetings and travel from Amgen, AstraZeneca, MSD, Roche, Tesaro. Nicoletta Colombo reports research grants from AstraZeneca, PharmaMar and Roche; honoraria for lectures from AstraZeneca, Tesaro, Novartis, Clovis Oncology, Merck Sharp and Dohme, GlaxoSmithKline and Eisai; honoraria for advisory boards from Roche, PharmaMar, AstraZeneca, Clovis Oncology, Merck Sharp and Dohme, GlaxoSmithKline, Tesaro, Pfizer, BioCad, Immunogen, Mersana, Eisai and Oncxema; and is a Steering Committee member on ESMO clinical guidelines and a Scientific Committee Chair for Acto Onlus. Trine Jakobi Nøttrup has nothing to disclose. Anne Floquet reports support for attending meetings and travel from AstraZeneca, GSK and PharmaMar. Ahmed El-Balat reports an advisory role for Roche, Clovis Oncology and Tesaro; lecture honoraria from Roche, Astra Zeneca and Olympus; travel support from AstraZeneca, PharmaMar and Teva. Giovanni Scambia reports grants/research support from MSD Italia S.r.l.; consulting fees from Johnson & Johnson, and TESARO Bio Italy S.r.l; and speaker's bureau fees from Clovis Oncology Italy Srl and MSD Italia Srl. Eva Maria Guerra Alia reports consulting fees from Roche, Clovis Oncology, GSK-Tesaro, PharmaMar, AstraZeneca and MSD; travel support from Roche, Baxter and GSK-Tesaro; participation on a data safety monitoring board or advisory board for Roche, Clovis Oncology, GSK-Tesaro, PharmaMar, AstraZeneca and MSD. Michel Fabbro reports honoraria from Astra Zeneca and GSK. Barbara Schmalfeldt reports consulting fees from AstraZeneca, Roche and MSD; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from AstraZeneca, Roche, Tesaro, GSK, MSD, and Clovis Oncology; travel support from AstraZeneca and Roche; participation on a data safety monitoring board or advisory board for AstraZeneca, Roche, GSK, MSD; and leadership or fiduciary role for Deutsche Gesellschaft für Gynäkologie und Geburtshilfe. Anne-Claire Hardy-Bessard reports consulting and advisory board fees from AstraZeneca, Clovis Oncology, GSK, Novartis, Pfizer, Roche and Seagen. Ingo Runnebaum reports lecture and advisory board fees from AstraZeneca, Tesaro, Clovis Oncology, and GlaxoSmithKline. Eric Pujade-Lauraine reports lecture fees and speaker's bureau fees from AstraZeneca, GSK, Tesaro, and Roche; lecture fees from Clovis and Pfizer; expert testimony fees from AstraZeneca; travel support from AstraZeneca and GSK; participation on a data safety monitoring board or advisory board from AstraZeneca, Roche and Incyte; and is employed by ARCAGY Research. Isabelle Ray-Coquard reports honoraria (self) from Abbvie, Agenus, Advaxis, BMS, PharmaMar, Genmab, Pfizer, AstraZeneca, Roche, GSK, MSD, Deciphera, Mersena, Merck Sereno, Novartis, Amgen, Tesaro and Clovis; honoraria (institution) from GSK, MSD, Roche and BMS; advisory/consulting fees from Abbvie, Agenus, Advaxis, BMS, PharmaMar, Genmab, Pfizer, AstraZeneca, Roche/Genentech, GSK, MSD, Deciphera, Mersana, Merck Sereno, Novartis, Amgen, Tesaro and Clovis; research grant/funding (self) from MSD, Roche and BMS; research grant/funding (institution) from MSD, Roche, BMS, Novartis, Astra Zeneca and Merck Sereno; and travel support from Roche and AstraZeneca and GSK.