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

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.

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“…ATALANTE/ENGOT-ov29 is the placebo-controlled randomized phase 3 study of atezolizumab combined with bevacizumab and platinum-based therapy for platinum-sensitive ovarian cancer [ 18 ]. Patients were randomly assigned 2:1 to atezolizumab (1,200 mg once every 3 weeks [Q3W] or equivalent) or placebo for up to 24 months, combined with bevacizumab and 6 cycles of chemotherapy doublet, stratified by platinum-free interval, PD-L1 status, and chemotherapy regimen.…”

Primary results and characterization of patients with exceptional outcomes in a phase 1b study combining PARP and MEK inhibition, with or without anti–PD‐L1, for BRCA wild‐type, platinum‐sensitive, recurrent ovarian cancer

“…Phase 3 results for PD-L1 inhibitors and chemotherapy (with or without bevacizumab) for ovarian cancer have been disappointing. [4][5][6][7] However, postulated synergy between PARPis and immune checkpoint inhibitors (ICIs) led to a phase 3 evaluation in ovarian cancer. 8 No benefit was observed with ICI added to chemotherapy and maintenance PARPi in the ANITA trial (ClinicalTrials.gov identifier NCT03598270), 9 suggesting that another targeted therapy may be needed to harness the synergy of PARPi and ICI.…”

TIM3 Checkpoint Inhibition Fails to Prolong Survival in Ovarian Cancer-Bearing Mice

“…Consequently, combination treatment of ICI with chemotherapy has been explored thoroughly for the treatment of ovarian cancer. Despite all efforts, four phase III studies were recently published showing no benefit [ 15 , 16 , 17 , 18 ]. More recently, disappointing interim results of the ANGOT-Ov41/ANITA phase III trial (NCT03598270) were presented at the ESMO Congress 2023, in which atezolizumab was combined with chemotherapy and PARP inhibition [ 19 ].…”