Atezolizumab Combined With Bevacizumab and Platinum-Based Therapy for Platinum-Sensitive Ovarian Cancer: Placebo-Controlled Randomized Phase III ATALANTE/ENGOT-ov29 Trial

Author(s): Jean-Emmanuel Kurtz, MD, PhD1; Eric Pujade-Lauraine, MD2; Ana Oaknin, MD3; Lisa Belin, MSc4; Katharina Leitner, MD5; David Cibula, MD6; Hannelore Denys, MD7; Ora Rosengarten, MD8; Manuel Rodrigues, MD9; Nikolaus de Gregorio, MD10,11; Jeronimo Martinez García, MD12; Edgar Petru, MD13; Roman Kocián, MD6; Ignace Vergote, MD14; Patricia Pautier, MD15; Barbara Schmalfeldt, MD16; Lydia Gaba, MD17; Stephan Polterauer, MD18; Marie-Ange Mouret Reynier, MD19; Jalid Sehouli, MD20,21; Cristina Churruca, MD22; Frédéric Selle, MD23; Florence Joly, MD24; Véronique D’Hondt, MD25; Émilie Bultot-Boissier, MD26; Coriolan Lebreton, MD27; Jean-Pierre Lotz, MD28; Rémy Largillier, MD29; Pierre-Etienne Heudel, MD30; and Florian Heitz, MD20,21,31; on behalf of the ATALANTE/ENGOT-ov29 Investigators
Source: DOI: 10.1200/JCO.23.00529 Journal of Clinical Oncology 41, no. 30 (October 20, 2023) 4768-4778.
Original Article
Maem Hussein MD

Dr. Maen Hussein's Thoughts

Adding Atezo to combination chemotherapy with bevacizumab did not meet the primary end point of PFS. Regardless of the PDL-1 status it was also more toxic. It seems that ovarian cancer is still immune to immunotherapy.

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.

Author Affiliations

1Department of Medical and Surgical Oncology & Hematology, ICANS, Strasbourg, France; 2Association de Recherche sur les CAncers dont GYnécologiques (ARCAGY)-GINECO, Paris, France; 3Gynaecologic Cancer Programme, Vall D’Hebron Institute of Oncology (VHIO), Hospital Universitario Vall d’Hebron, Vall d’Hebron Barcelona Hospital Campus, Barcelona, Spain; 4Biostatistics 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; 5Gynecology and Obstetrics Department, Medical University of Innsbruck, Innsbruck, Austria; 6Department of Obstetrics and Gynecology, General University Hospital in Prague, Charles University, Prague, Czech Republic; 7Department of Medical Oncology, University Hospital Ghent, Ghent, Belgium; 8Oncology Department, Shaare Zedek Medical Center, Jerusalem, Israel; 9Department of Medical Oncology and INSERM U830, Institut Curie, PSL Research University, Paris, France; 10Department of Obstetrics and Gynaecology, University Hospital Ulm, Ulm, Germany; 11SLK Klinikum Heilbronn, Heilbronn, Germany; 12Medical Oncology Department, Hospital Universitario Virgen Arrixaca (El Palmar) and Biomedical Research Institute of Murcia (IMIB), Murcia, Spain; 13Department of Gynecology and Obstetrics, Division of Gynecology, Medical University of Graz, Graz, Austria; 14Department of Gynecology, University Hospitals Leuven, Leuven Cancer Institute, Leuven, Belgium; 15Department of Medicine, Gustave Roussy, Villejuif, France; 16Department of Gynaecology and Gynaecologic Oncology, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany; 17Department 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; 18Department of Obstetrics and Gynecology, Medical University of Vienna, Vienna, Austria; 19Oncology Department, Centre Jean Perrin, Clermont-Ferrand, France; 20Department of Gynecology with Center for Oncological Surgery, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany; 21Berlin Institute of Health, Charité Medical University, Berlin, Germany; 22Department of Medical Oncology, Hospital Universitario Donostia, Donostia, Spain; 23Oncology Department, Groupe Hospitalier Diaconesses Croix Saint-Simon, Paris, France; 24Medical Oncology Department, Centre François Baclesse, Caen, France; 25Medical Oncology Department, Institut Régional du Cancer Montpellier (ICM), Montpellier, France; 26Oncology Department, Assistance Publique – Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Paris, France; 27Medical Oncology Department, Institut Bergonié, Bordeaux, France; 28Medical Oncology Service, Hôpital Tenon, Hôpitaux Universitaires de l’Est Parisien, Assistance Publique – Hôpitaux de Paris, Paris, France; 29Department of Medical Oncology, Centre Azuréen de Cancérologie, Mougins, France; 30Oncology Department, Centre Léon Bérard, Lyon, France; 31Department of Gynecology and Gynecologic Oncology, Evangelische Kliniken Essen-Mitte, Essen, Germany

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