Final overall survival (OS) results from the phase III PAOLA-1/ENGOT-ov25 trial evaluating maintenance olaparib (ola) plus bevacizumab (bev) in patients (pts) with newly diagnosed advanced ovarian cancer (AOC)

ABSTRACT

Background: In the PAOLA-1/ENGOT-ov25 (NCT02477644) primary analysis, adding ola to maintenance bev after first-line (1L) platinum-based chemotherapy (PBC) + bev led to a significant progression-free survival (PFS) benefit in AOC (HR 0.59, 95% CI 0.49-0.72;P<0.001), particularly in pts with homologous recombination deficiency (HRD+;BRCA1/2 mutation [BRCAm] and/or genomic instability;Ray-Coquard et al NEJM 2019). Here, we report the prespecified final OS analysis. Method(s) Pts with high-grade AOC, in response after PBC + bev, were randomized 21 to ola tablets (300 mg bid;up to 24 months [mo]) + bev (15 mg/kg q3w;15 mo total) or placebo [pbo] + bev. OS (intent-to-treat [ITT] population) was a key secondary endpoint, with analysis planned for 3 years after the primary analysis as part of hierarchical testing. Result(s) 537 pts were randomized to ola + bev and 269 to pbo + bev (median follow-up 61.7 and 61.9 mo, respectively;OS data maturity 55.3%). Median OS in the ITT population was 56.5 mo with ola + bev vs 51.6 mo with pbo + bev (HR 0.92, 95% CI 0.76-1.12;P=0.4118;OS at 5 y, 47.3 vs 41.5%). In HRD+ pts, OS was prolonged with ola + bev (HR 0.62, 95% CI 0.45-0.85;OS at 5 y, 65.5 vs 48.4%), with benefit in HRD+ pts with or without a tumour BRCAm (tBRCAm;Table). No benefit was seen in HRD- pts (HR 1.19, 95% CI 0.88-1.63). Subsequent PARP inhibitor therapy was received by 105 (19.6%) ola + bev pts vs 123 (45.7%) pbo + bev pts. Myelodysplastic syndrome, acute myeloid leukaemia and aplastic anaemia incidence, and new primary malignancy incidence, was respectively ola + bev, 9 pts [1.6%] and 22 pts [4.1%];pbo + bev, 6 pts [2.2%]) and 8 pts [2.9%]). [Formula presented] Conclusion(s) Despite a high proportion of pts in the control arm receiving a PARP inhibitor post-progression, ola + bev provided a clinically meaningful improvement in OS for 1L HRD+ pts with and without a tBRCAm, confirming ola + bev as standard of care in this setting. Clinical trial identification NCT02477644. Editorial acknowledgement Medical writing assistance was provided by Rachel Dodd, PhD, at Cence, funded by AstraZeneca and Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. Legal entity responsible for the study AstraZeneca. Funding(s) ARCAGY Research, AstraZeneca, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, and F. Hoffmann-La Roche. Disclosure I.L. Ray-Coquard Financial Interests, Personal, Advisory Board Roche, GSK, AstraZeneca, Mersana, Deciphera, Amgen, Oxnea, Merck Sereno, Agenus, Novartis, Macrogenics, Clovis, EQRX, adaptimmun, Esai, SUTRO;Financial Interests, Institutional, Other, COLIBRI translational research BMS;Financial Interests, Institutional, Advisory Board, translational research NEOPREMBROV trial MSD;Non-Financial Interests, Personal, Principal Investigator PAOLA1;Non-Financial Interests, Personal, Other, President GINECO. K. Fujiwara Financial Interests, Personal, Other, Consulting fees and grant support Pfizer, Eisai, Merck Sharp & Dohme, Taiho, Zeria, Chugai Pharmaceutical, Genmab, Takeda Pharmaceutical;Financial Interests, Personal, Research Grant Immunogen, Oncotherapy, Regeneron;Financial Interests, Personal, Other, Consulting fees Novartis, Kyowa Hakko Kirin, Daiichi Sankyo, Mochida Pharmaceutical, NanoCarrier. A. Leary Financial Interests, Personal, Advisory Board Zentalis;Financial Interests, Personal, Invited Speaker, Educational GSK, Medscape, Onko+;Financial Interests, Institutional, Other, Steering committee MSD;Financial Interests, Institutional, Advisory Board GSK, AZ, Clovis, Ability Pharma, MSD, Tesaro, Merck Serono, Apmonia, Blueprint;Financial Interests, Institutional, Invited Speaker, Educational Kephren publishing;Financial Interests, Institutional, Other, Consultancy Orion;Financial Interests, Institutional, Invited Speaker Tesaro, AZ, Clovis;Financial Interests, Personal, Other, Consultancy GLG;Financial Interests, Institutional, Research Grant, PI translational research ARCAGY-GINECO, Sanofi, A ;Financial Interests, Institutional, Funding, CI clinical trial AZ;Financial Interests, Institutional, Research Grant, Int CI clinical trial OSE immuno;Financial Interests, Institutional, Funding, PI clinical trial Agenus, BMS, Iovance, GSK;Financial Interests, Institutional, Funding, PI 5 clinical trials Roche;Financial Interests, Institutional, Funding, PI 2 clinical trials AZ;Financial Interests, Institutional, Funding, PI 3 clinical trials and steering committee MSD;Non-Financial Interests, Institutional, Other, Academic research project Owkin, LXRepair;Non-Financial Interests, Personal, Proprietary Information, IDMC member Clovis;Non-Financial Interests, Personal, Proprietary Information, IDMC chair Pfizer. S. Pignata Financial Interests, Personal, Advisory Board Roche, AZ, MSD, Clovis, GSK, PharmaMar;Financial Interests, Institutional, Funding: Roche, MSD, Pfizer, AZ. A.J. Gonzalez Martin Financial Interests, Personal, Advisory Board Amgen, AstraZeneca, Clovis, GSK, Genmab, Alkermes, Sutro, Roche, Sotio, PharmaMar, Oncoinvent, Novartis, Mersana, MSD, Macrogenics;Financial Interests, Personal, Invited Speaker GSK, AstraZeneca, Clovis, Roche, Novocure, MSD;Financial Interests, Institutional, Invited Speaker, PI of ANITA trial GSK, Roche;Financial Interests, Personal, Invited Speaker, Member of ENGOT ov43-SC MSD;Financial Interests, Institutional, Invited Speaker, ENGOT PI of EPIK-O trial Novartis;Financial Interests, Institutional, Invited Speaker, ENGOT PI of AVB-500 phase III trial ARAVIVE. G. Bogner Financial Interests, Personal, Advisory Board AstraZeneca, Roche and GSK;Financial Interests, Personal, Other, Medical conferences AstraZeneca, Roche and GSK. I.B. Vergote Financial Interests, Personal, Advisory Board, Consulting Agenus (2021), Aksebio China (2021), AstraZeneca (2021-2022), Bristol Myers Squibb (2021), Deciphera Pharmaceuticals (2021), Eisai (2021), F. Hoffmann-La Roche Ltd. (2021), Genmab (2021), GSK (2021), Immunogen Inc. (2021-2022), Jazzpharma (2021-2022), Karyopharm (2021), MSD (2021-2022), Novocure (2020-2022), Novartis (2021), Oncoinvent AS (2021-2022), Seagen (2021), Sotio a.s. (2021-2022);Financial Interests, Institutional, Advisory Board, Consulting AstraZeneca (2019-2020), eciphera Pharmaceuticals (2020), Elevar Therapeutics (2020), F. Hoffmann-La Roche Ltd. (2019-2020), Genmab (2019-2020), GSK (2019-2020), Mersana (2020), MSD (2019-2020), Oncoinvent AS (2019-2020), Sotio a.s. 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Colombo Financial Interests, Personal, Advisory Board, Various Roche, PharmaMar, AstraZeneca, MSD/Merck, Clovis Oncology, Tesaro, GSK, Pfizer, Takeda, BIOCAD, Immunogen, Mersana;Financial Interests, Personal, Invited Speaker, Congress, Symposia, Lectures AstraZeneca, Tesaro;Financial Interests, Personal, Invited Speaker, Lectures Novartis;Financial Interests, Personal, Advisory Board, Lectures Eisai;Financial Interests, Personal, Advisory Board, Advisory role Nuvation Bio, Pieris;Financial Interests, Personal, Advisory Board, Advisory Role Onxerna;Financial Interests, Institutional, Research Grant AstraZeneca, PharmaMar, Roche;Non-Financial Interests, Personal, Other, Sterring committee member Clinical Guidelines ESMO;Non-Financial Interests, Personal, Leadership Role, Chair, Scientific Committee ACTO( Alleanza contro il tumore ovarico). J. Maenpaa Financial Interests, Personal, Other, Honoraria AstraZeneca and GSK. F. Selle Financial Interests, Personal, Other, Honoraria AstraZeneca, GSK Tesaro, MSD, Sandoz (Novartis), and Clovis Oncology;Financial Int rests, Institutional, Funding: Roche, GSK Tesaro, AstraZeneca, Immunogen, MSD, Incyte, and Agenus. B. Schmalfeldt Financial Interests, Personal, Other, Honoraria Roche, AstraZeneca, Tesaro, Clovis, GSK, MSD;Financial Interests, Personal, Advisory Role Roche, AstraZeneca, Tesaro, Clovis, GSK, MSD;Financial Interests, Personal, Speaker's Bureau Roche, AstraZeneca, Tesaro, Clovis, GSK, MSD;Financial Interests, Personal, Funding: Roche, AstraZeneca, Tesaro, Clovis, GSK, MSD;Financial Interests, Personal, Other, Travel or accommodation expenses Roche, AstraZeneca, Tesaro. G. Scambia Financial Interests, Personal, Invited Speaker, Speaker Johnson & Johnson, AstraZeneca&MSD, Olympus Europa, Baxter Healthcare, Intuitive Surgical Inc., GlaxoSmithKline;Financial Interests, Personal, Expert Testimony, Trainer Covidien AG (Medtronic company);Financial Interests, Institutional, Invited Speaker, 'IsoMSLN' in Ovarian Cancer and Malignant Pleural Mesothelioma Kiromic;Financial Interests, Institutional, Invited Speaker, Roll-over study for patients who have completed a previous cancer study with olaparib and who the investigator believes can benefit from continued treatment - ROSY-O AstraZeneca;Financial Interests, Institutional, Invited Speaker, CATCH-R Roll-over study to provide continuous access to clinical therapy with rucaparib. Clovis Oncology;Financial Interests, Institutional, Invited Speaker, Phase 3, multicenter, placebo-controlled clinical study comparing chemo-immunotherapy (paclitaxel-carboplatin-oregovomab) versus chemotherapy (paclitaxel-carboplatin-placebo) in patients with advanced epithelial ovarian, tubal cancer of fallopian or peritoneal (FLORA-5) Oncoquest Pharmaceuticals Inc.;Financial Interests, Institutional, Invited Speaker, Phase 2b randomized, open-label,active comparator, parallel-group, multicenter study designed to evaluate the efficacy and safety of three different doses of the P2X3 receptor antagonist (BAY 1817080) versus placebo and Elagolix 150 mg in women with symptomatic endometriosis Bayer AG;Financial Interests, Institutional, Invited Speaker, Usability of ITE transducers for sending electric fields for tumor treatment (TTFields) Novocure Ltd.;Financial Interests, Institutional, Invited Speaker Phase III, multicentre, open-label extension trial to evaluate long-term safety and efficacy in patients with advanced cancers currently undergoing treatment or in follow-up in a pembrolizumab trial. 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A. lortholary Financial Interests, Personal, Advisory Board AstraZeneca, MSD and Tesaro;Financial Interests, Personal, Speaker's Bureau Clovis Oncology, and Roche;Financial Interests, Personal, Other, Participation in a medical congress Novartis, Pfizer, MSD, Lilly and Roche. E. Pujade-Lauraine Financial Interests, Personal, Other, Lecture fees AstraZeneca, Tesaro, Roche, Clovis Oncology, Incyte, Pfizer;Financial Interests, Personal, Speaker's Bureau AstraZeneca, Tesaro, and Roche;Financial Interests, Personal, Other, Travel/accommodation AstraZeneca, Tesaro, and Roche;Financial Interests, Personal, Full or part-time Employment ARCAGY Research. P. Harter Financial Interests, Personal, Advisory Board, Value includes honoraria for lectures AstraZeneca;Financial Interests, Personal, Advisory Board, includes honoraria for lectu es GSK, Roche, MSD;Financial Interests, Personal, Invited Speaker Amgen, Stryker, Zailab;Financial Interests, Personal, Advisory Board Clovis, Immunogen;Financial Interests, Personal, Other, IDMC member Sotio;Financial Interests, Institutional, Invited Speaker AstraZeneca, Roche, GSK, Genmab, Immunogen;Financial Interests, Institutional, Funding: Seagen, Clovis. All other authors have declared no conflicts of interest. Copyright © 2022