Updated progression-free survival and final overall survival with 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.

In the PAOLA-1/ENGOT-ov25 trial (NCT02477644), adding maintenance olaparib to bevacizumab provided a substantial progression-free survival benefit in patients with newly diagnosed advanced ovarian cancer and homologous recombination deficiency (HRD)-positive tumors, irrespective of clinical risk. Subsequently, a clinically meaningful improvement in overall survival was reported with olaparib plus bevacizumab in the HRD-positive subgroup. We report updated progression-free survival and overall survival by clinical risk and HRD status. Patients in clinical response after first-line platinum-based chemotherapy plus bevacizumab received maintenance olaparib (up to 24 months) plus bevacizumab (up to 15 months in total) or placebo plus bevacizumab. This Of 806 randomized patients, 74% were higher-risk and 26% were lower-risk. In higher-risk HRD-positive patients, the hazard ratio (HR) for progression-free survival was 0.46 (95% confidence interval (95% CI) 0.34 to 0.61), with 5-year progression-free survival of 35% with olaparib plus bevacizumab versus 15% with bevacizumab alone; and the HR for overall survival was 0.70 (95% CI 0.50 to 1.00), with 5-year overall survival of 55% versus 42%, respectively. In lower-risk HRD-positive patients, the HR for progression-free survival was 0.26 (95% CI 0.15 to 0.45), with 5-year progression-free survival of 72% with olaparib plus bevacizumab versus 28% with bevacizumab alone; and the HR for overall survival was 0.31 (95% CI 0.14 to 0.66), with 5-year overall survival of 88% versus 61%, respectively. No benefit was seen in HRD-negative patients regardless of clinical risk. This

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Competing interests: Domenica Lorusso reports consultancy fees (personal) from Amgen, AstraZeneca, Clovis Oncology, Genmab, GSK, Immunogen, MSD, PharmaMar, and Seagen; membership on an advisory board (personal) for AstraZeneca, Clovis Oncology, Corcept, Genmab, GSK, Immunogen, Merck Serono, MSD, Oncoinvest, PharmaMar, Seagen, and Sutro; and research funding (institutional) from AstraZeneca, Clovis Oncology, Genmab, GSK, Immunogen, Incyte, MSD, Novartis, PharmaMar, Roche, and Seagen; and travel support from Roche, PharmaMar, AstraZeneca, Clovis Oncology, and GSK. Marie-Ange Mouret-Reynier reports board membership (personal and institution) for Pfizer, Lilly, Novartis, MSD, and AstraZeneca; and research funding (personal and institution) from Pfizer, Lilly, Novartis, MSD, and AstraZeneca. Philipp Harter reports honoraria from Amgen, AstraZeneca, GSK, Roche, Sotio, Stryker, Zai Lab, MSD, Clovis, Eisai, Mersana, and Exscientia; membership on an advisory board for AstraZeneca, Roche, GSK, Clovis, Immunogen, MSD, Miltenyi, Novartis, and Eisai; and research funding (institutional) from AstraZeneca, Roche, GSK, Genmab, Immunogen, Seagen, Clovis, and Novartis. Claire Cropet reports no conflicts of interest. Cristina Caballero reports no conflicts of interest. Pia Wolfrum-Ristau reports no conflicts of interest.Toyomi Satoh reports no conflicts of interest. Ignace Vergote reports consulting fees (personal) from Agenus, Akesobio, AstraZeneca, BMS, Deciphera Pharmaceuticals, Eisai, Elevar Therapeutics, Exelixis, Roche, Genmab, GSK, Immunogen, Jazz Pharmaceuticals, Karyopharm, Mersana, Molecular Partners, MSD, Novocure, Novartis, Oncoinvent, OncXerna, Regeneron, Sanofi, Seagen, Sotio, Verastem Oncology, and Zentalis; contracted research (via KULeuven; institution) for Oncoinvent AS; corporate sponsored research (institution) from Amgen and Roche; and travel support (personal) from Karyopharm, Genmab, and Novocure.Gabriella Parma reports no conflicts of interest. Trine Jakobi Nøttrup reports no conflicts of interest. Coriolan Lebreton reports honoraria (personal) from Eisai, Clovis Oncology, MSD, and GSK. Peter A Fasching reports membership on an advisory board (personal) for Agendia, AstraZeneca, Daiichi-Sankyo, Eisai, Hexal, Lilly, MSD, Novartis, Pfizer, Pierre Fabre, Roche, Sanofi Aventis, and Seagen; invited speaker fees (personal) from AstraZeneca, Daiichi-Sankyo, Eisai, Gilead, Lilly, MSD, Novartis, and Seagen; and medical writing support (personal) from Roche. Carmela Pisano reports membership on an advisory board (personal) for AstraZeneca, MSD and GSK; and honoraria (personal) from Clovis Oncology. Luis Manso reports no conflicts of interest. Hugues Bourgeois reports no conflicts of interest. Ingo Runnebaum reports no conflicts of interest. Claudio Zamagni reports reports grants or contract to self from Amgen, Celgene, Daiichi, Eisai, Eli Lilly, GSK, MSD, and PharmaMar; grants or contract to self and institution from AstraZeneca, Instituto Gentili, Novartis, Pfizer, Pierre Fabre, Roche, Seagen, Tesaro, and Teva; support for attending meetings and/or travel from Celgene, Instituto Gentili, Novartis, Pfizer, PharmaMar, Pierre Fabre, Roche, and Tesaro; participation on a data safety monitoring board or advisory board for Amgen, AstraZeneca, Celgene, Daiichi, Eisai, Eli Lilly, GSK, MSD, Novartis, Pfizer, PharmaMar, QuintilesIMS, Roche, and Tesaro; and other financial or non-interests for Amgen, AstraZeneca, Daiichi, GSK, MSD, Novartis, Pfizer, PharmaMar, QuintilesIMS, Roche, and Tesaro. Anne-Claire Hardy-Bessard reports membership on an advisory board (personal) for MSD, AstraZeneca, GSK, Pfizer, and Novartis. Andreas Schnelzer reports no conflicts of interest. Michel Fabbro reports honoraria from GSK. Barbara Schmalfeldt reports honoraria from Roche, AstraZeneca, Tesaro, Clovis, GSK, and MSD; consultancy or advisory roles from Roche, AstraZeneca, Tesaro, Clovis, GSK, and MSD; membership of a speaker’s bureau for Roche, AstraZeneca, Tesaro, Clovis, GSK, and MSD; research funding from Roche, AstraZeneca, Tesaro, Clovis, GSK, and MSD; and funding for travel or accommodation expenses from Roche, AstraZeneca, and Tesaro. Dominique Berton reports no conflicts of interest. Antje Belau reports honoraria from Roche, AstraZeneca, Clovis, MSD, Daiichi Sankyo Company, Lilly, and Seagen; advisory roles for Pfizer, Roche, AstraZeneca, MSD, Lilly, Daiichi Sankyo Company, and Seagen; and funding for travel or accommodation expenses from Roche, AstraZeneca, and Daiichi Sankyo Company. Jean-Pierre Lotz reports no conflicts of interest. Martina Gropp-Meier reports no conflicts of interest. Laurence Gladieff reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from AstraZeneca, Clovis, Eisai, GSK, and MSD; and participation on an advisory board for AstraZeneca, GSK, and MSD. Hans-Joachim Lück reports participation on advisory boards for AstraZeneca, GSK, Seagen, Gilead, Novartis, and Lilly and speaker roles for AstraZeneca, Lilly, Gilead, Pfizer, and Novartis. Sophie Abadie-Lacourtoisie reports no conflicts of interest. Eric Pujade-Lauraine reports membership on an advisory board (personal) for Roche, GSK, and AstraZeneca; Independent Data Monitoring Committee board membership (personal) for Agenus and Incyte; and employment (personal) at ARCAGY Research. Isabelle Ray-Coquard reports honoraria (personal) from Abbvie, Agenus, Advaxis, BMS, PharmaMar, Genmab, Pfizer, AstraZeneca, Roche, GSK, MSD, Deciphera, Mersena, Merck Sereno, Novartis, Amgen, Tesaro, and Clovis Oncology; 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, Mersena, Merck Sereno, Novartis, Amgen, Tesaro, and Clovis Oncology; research grant/funding (personal) from MSD, Roche, and BMS; research grant/funding (institution) from MSD, Roche, BMS, Novartis, AstraZeneca, and Merck Sereno; and travel support from Roche, AstraZeneca, and GSK.