DOI: 10.1200/jco.23.00529 ISSN:

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

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