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

• Published in: Journal of clinical oncology Vol. 41; no. 30; pp. 4768 - 4778
• Main 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
• Format: Journal Article
• Language: English
• Published: United States American Society of Clinical Oncology 20.10.2023; Wolters Kluwer Health
• Subjects: Antineoplastic Combined Chemotherapy Protocols - therapeutic use; B7-H1 Antigen - therapeutic use; Bevacizumab; Cancer; Carcinoma, Ovarian Epithelial - drug therapy; Female; Humans; Life Sciences; Neoplasm Recurrence, Local - drug therapy; ORIGINAL REPORTS; Ovarian Neoplasms - drug therapy; Ovarian Neoplasms - pathology; Platinum - therapeutic use; Quality of Life
• ISSN: 0732-183X; 1527-7755; 1527-7755
• DOI: 10.1200/JCO.23.00529

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. 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). 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; = .041; median 13.5 11.3 months, respectively) or PD-L1-positive (HR, 0.86; 95% CI, 0.63 to 1.16; = .30; median 15.2 13.1 months, respectively) populations. The immature overall survival (OS) HR was 0.81 (95% CI, 0.65 to 1.01; median 35.5 30.6 months with atezolizumab 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% 8%, respectively). 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.