Atezolizumab Combined With Bevacizumab and Platinum-Based Therapy for Platinum-Sensitive Ovarian Cancer: Placebo-Controlled Randomized Phase III ATALANTE/ENGOT-ov29 Trial
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Published:2023-10-20
Issue:30
Volume:41
Page:4768-4778
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ISSN:0732-183X
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Container-title:Journal of Clinical Oncology
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language:en
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Short-container-title:JCO
Author:
Kurtz Jean-Emmanuel1ORCID, Pujade-Lauraine Eric2ORCID, Oaknin Ana3ORCID, Belin Lisa4, Leitner Katharina5ORCID, Cibula David6ORCID, Denys Hannelore7ORCID, Rosengarten Ora8, Rodrigues Manuel9ORCID, de Gregorio Nikolaus1011, Martinez García Jeronimo12ORCID, Petru Edgar13, Kocián Roman6ORCID, Vergote Ignace14ORCID, Pautier Patricia15, Schmalfeldt Barbara16, Gaba Lydia17ORCID, Polterauer Stephan18ORCID, Mouret Reynier Marie-Ange19, Sehouli Jalid2021, Churruca Cristina22, Selle Frédéric23, Joly Florence24ORCID, D'Hondt Véronique25ORCID, Bultot-Boissier Émilie26, Lebreton Coriolan27ORCID, Lotz Jean-Pierre28ORCID, Largillier Rémy29, Heudel Pierre-Etienne30ORCID, Heitz Florian202131ORCID, 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.,
Affiliation:
1. Department of Medical and Surgical Oncology & Hematology, ICANS, Strasbourg, France 2. Association de Recherche sur les CAncers dont GYnécologiques (ARCAGY)-GINECO, Paris, France 3. Gynaecologic Cancer Programme, Vall D'Hebron Institute of Oncology (VHIO), Hospital Universitario Vall d'Hebron, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain 4. Biostatistics and Public Health Department, Sorbonne Université, INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique, Assistance Publique – Hôpitaux de Paris, Hôpitaux Universitaires Pitié Salpětriére – Charles Foix, Paris, France 5. Gynecology and Obstetrics Department, Medical University of Innsbruck, Innsbruck, Austria 6. Department of Obstetrics and Gynecology, General University Hospital in Prague, Charles University, Prague, Czech Republic 7. Department of Medical Oncology, University Hospital Ghent, Ghent, Belgium 8. Oncology Department, Shaare Zedek Medical Center, Jerusalem, Israel 9. Department of Medical Oncology and INSERM U830, Institut Curie, PSL Research University, Paris, France 10. Department of Obstetrics and Gynaecology, University Hospital Ulm, Ulm, Germany 11. SLK Klinikum Heilbronn, Heilbronn, Germany 12. Medical Oncology Department, Hospital Universitario Virgen Arrixaca (El Palmar) and Biomedical Research Institute of Murcia (IMIB), Murcia, Spain 13. Department of Gynecology and Obstetrics, Division of Gynecology, Medical University of Graz, Graz, Austria 14. Department of Gynecology, University Hospitals Leuven, Leuven Cancer Institute, Leuven, Belgium 15. Department of Medicine, Gustave Roussy, Villejuif, France 16. Department of Gynaecology and Gynaecologic Oncology, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany 17. Department of Medical Oncology, Translational Genomics and Targeted Therapeutics in Solid Tumors, Hospital Clínic de Barcelona, Institut D'Investigacions Biomédiques August Pi I Sunyer (IDIBAPS), Barcelona, Spain 18. Department of Obstetrics and Gynecology, Medical University of Vienna, Vienna, Austria 19. Oncology Department, Centre Jean Perrin, Clermont-Ferrand, France 20. Department of Gynecology with Center for Oncological Surgery, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany 21. Berlin Institute of Health, Charité Medical University, Berlin, Germany 22. Department of Medical Oncology, Hospital Universitario Donostia, Donostia, Spain 23. Oncology Department, Groupe Hospitalier Diaconesses Croix Saint-Simon, Paris, France 24. Medical Oncology Department, Centre François Baclesse, Caen, France 25. Medical Oncology Department, Institut Régional du Cancer Montpellier (ICM), Montpellier, France 26. Oncology Department, Assistance Publique – Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Paris, France 27. Medical Oncology Department, Institut Bergonié, Bordeaux, France 28. Medical Oncology Service, Hôpital Tenon, Hôpitaux Universitaires de l'Est Parisien, Assistance Publique – Hôpitaux de Paris, Paris, France 29. Department of Medical Oncology, Centre Azuréen de Cancérologie, Mougins, France 30. Oncology Department, Centre Léon Bérard, Lyon, France 31. Department of Gynecology and Gynecologic Oncology, Evangelische Kliniken Essen-Mitte, Essen, Germany
Abstract
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.
Publisher
American Society of Clinical Oncology (ASCO)
Subject
Cancer Research,Oncology
Cited by
6 articles.
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