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.

Association de Recherche sur les CAncers dont GYnécologiques GINECO Paris France

Berlin Institute of Health Charité Medical University Berlin Germany

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

Department of Gynaecology and Gynaecologic Oncology University Medical Centre Hamburg Eppendorf Hamburg Germany

Department of Gynecology and Gynecologic Oncology Evangelische Kliniken Essen Mitte Essen Germany

Department of Gynecology and Obstetrics Division of Gynecology Medical University of Graz Graz Austria

Department of Gynecology University Hospitals Leuven Leuven Cancer Institute Leuven Belgium

Department of Gynecology with Center for Oncological Surgery Charité Universitätsmedizin Berlin Corporate Member of Freie Universität Berlin Humboldt Universität zu Berlin Berlin Germany

Department of Medical and Surgical Oncology and Hematology ICANS Strasbourg France

Department of Medical Oncology and INSERM U830 Institut Curie PSL Research University Paris France

Department of Medical Oncology Centre Azuréen de Cancérologie Mougins France

Department of Medical Oncology Hospital Universitario Donostia Donostia Spain

Department of Medical Oncology Translational Genomics and Targeted Therapeutics in Solid Tumors Hospital Clínic de Barcelona Institut D'Investigacions Biomédiques August Pi 1 Sunyer Barcelona Spain

Department of Medical Oncology University Hospital Ghent Ghent Belgium

Department of Medicine Gustave Roussy Villejuif France

Department of Obstetrics and Gynaecology University Hospital Ulm Ulm Germany

Department of Obstetrics and Gynecology General University Hospital Prague Charles University Prague Czech Republic

Department of Obstetrics and Gynecology Medical University of Vienna Vienna Austria

Gynaecologic Cancer Programme Vall D'Hebron Institute of Oncology Hospital Universitario Vall d'Hebron Vall d'Hebron Barcelona Hospital Campus Barcelona Spain

Gynecology and Obstetrics Department Medical University of Innsbruck Innsbruck Austria

Medical Oncology Department Centre François Baclesse Caen France

Medical Oncology Department Hospital Universitario Virgen Arrixaca Murcia Spain

Medical Oncology Department Institut Bergonié Bordeaux France

Medical Oncology Department Institut Régional du Cancer Montpellier Montpellier France

Medical Oncology Service Hôpital Tenon Hôpitaux Universitaires de l'Est Parisien Assistance Publique Hôpitaux de Paris Paris France

Oncology Department Assistance Publique Hôpitaux de Paris Hôpital Européen Georges Pompidou Paris France

Oncology Department Centre Jean Perrin Clermont Ferrand France

Oncology Department Centre Léon Bérard Lyon France

Oncology Department Groupe Hospitalier Diaconesses Croix Saint Simon Paris France

Oncology Department Shaare Zedek Medical Center Jerusalem Israel

SLK Klinikum Heilbronn Heilbronn Germany

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$a 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.

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