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
  • ATALANTE/ENGOT-ov29 Investigators

Related Research units

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.

Bibliographical data

Original languageEnglish
ISSN0732-183X
DOIs
Publication statusPublished - 20.10.2023
PubMed 37643382