Atezolizumab Combined With Bevacizumab and Platinum-Based Therapy for Platinum-Sensitive Ovarian Cancer: Placebo-Controlled Randomized Phase III ATALANTE/ENGOT-ov29 Trial
Authors: Kurtz Jean-Emmanuel , Pujade-Lauraine Eric , Oaknin Ana , Belin Lisa , Leitner Katharina , Cibula David , Denys Hannelore , Rosengarten Ora , Rodrigues Manuel , de Gregorio Nikolaus , Martinez García Jeronimo , Petru Edgar , Kocián Roman , Vergote Ignace , Pautier Patricia , Schmalfeldt Barbara , Gaba Lydia , Polterauer Stephan , Mouret Reynier Marie-Ange , Sehouli Jalid , Churruca Cristina , Selle Frédéric , Joly Florence , D'Hondt Véronique , Bultot-Boissier Émilie , Lebreton Coriolan , Lotz Jean-Pierre , Largillier Rémy , Heudel Pierre-Etienne , Heitz Florian ,   on behalf of the ATALANTE/ENGOT-ov29 Investigators, Kurtz J.-E. , Abadie-Lacourtoisie S. , Abdeddaim C. , Alexandre J. , Augereau P. , Avenin D. , Azemar M. , Baba-Hamed N. , Bally O. , Barriere J. , Bazan F. , Berton D. , Bonichon-Lamichhane N. , Bonnin N. , Boughalem E. , Boustany Grenier R. , Brachet P.-E. , Brocard F. , Bultot-Boissier E. , Cappiello-Bataller M.A. , Castanie H. , Chaigneau L. , Chakiba C. , Chocteau-Bouju D. , Combe P. , Comte A. , Coquan E. , Costan C. , Cottu P. , Crouzet L. , Cure H. , Dauba J. , Dawood H. , De Cock L. , De La Motte Rouge T. , Debelleix C. , Delbaldo C. , Demarchi M. , Deslandres M. , Despax R. , D'Hondt V. , Dillies-Legrain A.F. , Donnadieu A. , Dubot C. , Extra J.-M. , Fabbro M. , Falandry C. , Fiteni F. , Floquet A. , Follana P. , Frenel J.S. , Freyer G. , Garbay-Decoopman D. , Gavoille C. , Girre V. , Gladieff L. , Goldwasser F. , Gratet A. , Grenier J. , Hardy-Bessard A.-C. , Heudel P.-E. , Joly F. , Jouinot A. , Kalbacher E. , Kaminsky M.-C. , Lancry-Lecomte L. , Largillier R. , Le Du F. , Leary A. , Lebreton C. , Lefeuvre-Plesse C. , Lesoin A. , L'Haridon T. , Long J. , Lortholary A. , Lotz J.-P. , Mansi L. , Martin-Babau J. , Martinez M. , Medioni J. , Meriaux E. , Meunier J. , Moïse L. , Moulin J.-F. , Mouret-Reynier M.-A. , Mousseau M. , Pautier P. , Peron J. , Perrin C. , Petit T. , Petran D. , Priou F. , Provansal M. , Raban N. , Ray-Coquard I. , Regnault De La Mothe P. , Riedl C. , Rodrigues M. , Roemer-Becuwe C. , Sabatier R. , Savinelli F. , Sebbag C. , Selle F. , Soulie P. , Spaeth D. , Sverdlin R. , Timar-David M. , Tredan O. , Tresca P. , Trillet-Lenoir V. , Valentin T. , Vano Y.A. , You B. , Heitz F. , Bronger H. , Buderath P. , De Gregorio N. , Fehm T. , Grischke E.-M. , Gropp-Meier M. , Hartkopf A. , Jackisch C. , Koegel M. , Mueller A. , Park-Simon T.-W. , Runnebaum I. , Schochter F. , Schmalfeldt B. , Schnappauf B. , Sehouli J. , Trillsch F. , Wimberger P. , Oaknin A. , Alarcon J.D. , Alonso S. , Alonso Herrero A. , Barretina P. , Casado A. , Churruca C. , Fernandez I. , Gaba L. , Garcia-Donas J. , Gonzalez S. , Marquina G. , Martinez-García J. , Redondo A. , Vicente D. , Marth C. , Aust S. , Petru E. , Reinthaller A. , Schauer C. , Cibula D. , Vergote I. , Altintas S. , Denys H. , Van Nieuwenhuysen E. , Rosengarten O. 
Published: August 2023

PURPOSE Platinum-based doublets with concurrent and maintenance bevacizumab are standard therapy for ovarian cancer (OC) relapsing after a platinum-free interval (PFI) >6 months. Immunotherapy may be synergistic with bevacizumab and chemotherapy. PATIENTS AND METHODS ATALANTE/ENGOT-ov29 (ClinicalTrials.gov identifier: NCT02891824 ), a placebo-controlled double-blinded randomized phase III trial, enrolled patients with recurrent epithelial OC, one to two previous chemotherapy lines, and PFI >6 months. Eligible patients were randomly assigned 2:1 to atezolizumab (1,200 mg once every 3 weeks or equivalent) or placebo for up to 24 months, combined with bevacizumab and six cycles of chemotherapy doublet, stratified by PFI, PD-L1 status, and chemotherapy regimen. Coprimary end points were investigator-assessed progression-free survival (PFS) in the intention-to-treat (ITT) and PD-L1–positive populations (alpha .025 for each population). RESULTS Between September 2016 and October 2019, 614 patients were randomly assigned: 410 to atezolizumab and 204 to placebo. Only 38% had PD-L1–positive tumors. After 3 years' median follow-up, the PFS difference between atezolizumab and placebo did not reach statistical significance in the ITT (hazard ratio [HR], 0.83; 95% CI, 0.69 to 0.99; P = .041; median 13.5 v 11.3 months, respectively) or PD-L1–positive (HR, 0.86; 95% CI, 0.63 to 1.16; P = .30; median 15.2 v 13.1 months, respectively) populations. The immature overall survival (OS) HR was 0.81 (95% CI, 0.65 to 1.01; median 35.5 v 30.6 months with atezolizumab v placebo, respectively). Global health-related quality of life did not differ between treatment arms. Grade ≥3 adverse events (AEs) occurred in 88% of atezolizumab-treated and 87% of placebo-treated patients; grade ≥3 AEs typical of immunotherapy were more common with atezolizumab (13% v 8%, respectively). CONCLUSION ATALANTE/ENGOT-ov29 did not meet its coprimary PFS objectives in the ITT or PD-L1–positive populations. OS follow-up continues. Further research on biopsy samples is warranted to decipher the immunologic landscape of late-relapsing OC.