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Clinical Trial
. 2023 Oct 20;41(30):4768-4778.
doi: 10.1200/JCO.23.00529. Epub 2023 Aug 29.

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

Collaborators, Affiliations
Clinical Trial

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 et al. J Clin Oncol. .

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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Conflict of interest statement

The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated unless otherwise noted. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/jco/authors/author-center.

Open Payments is a public database containing information reported by companies about payments made to US-licensed physicians (Open Payments).

Florian Heitz

Honoraria: Roche, AstraZeneca, Tesaro/GSK

Consulting or Advisory Role: Roche, AstraZeneca, GlaxoSmithKline, Novocure, PharmaMar

Research Funding: AstraZeneca (Inst), Amedes (Inst)

No other potential conflicts of interest were reported.

Figures

FIG 1.
FIG 1.
CONSORT diagram. ITT, intention-to-treat.
FIG 2.
FIG 2.
PFS: (A) ITT population (N = 614); (B) PD-L1–positive population (n = 233). PFS was defined as the interval between random assignment and the date of first objective radiologic disease progression (investigator-assessed per RECIST version 1.1) or death. Sensitivity analyses in the per-protocol population showed consistent results (ITT per-protocol population: HR, 0.82; 95% CI, 0.69 to 0.99; P = .037; median 13.6 months with atezolizumab v 11.3 months with placebo). Shaded area for each line represents the 95% CI. HR, hazard ratio; ITT, intention-to-treat; PFS, progression-free survival.
FIG 3.
FIG 3.
Subgroup analysis of PFS (intention-to-treat population). Subgroup analyses according to randomization stratification factors categorized patients for PFI, PD-L1 status, and chemotherapy cohort as recorded in the electronic case report form. CA-125, cancer antigen-125; HR, hazard ratio; PFS, progression-free survival; PLD, pegylated liposomal doxorubicin; SLD, sum of largest diameter.
FIG 4.
FIG 4.
Secondary end points. (A) Time to second subsequent therapy in the ITT population. (B) OS (interim analysis) in the ITT population. Shaded area for each line represents the 95% CI. HR, hazard ratio; ITT, intention-to-treat; OS, overall survival; TSST, time from random assignment to start of second subsequent therapy or death.
FIG A1.
FIG A1.
(A) TFST in the intention-to-treat population. (B) TFST in the PD-L1–positive population. (C) OS in the PD-L1–positive population (interim analysis). HR, hazard ratio; OS, overall survival; TFST, time to first subsequent therapy.
FIG A2.
FIG A2.
Mean change from baseline in HRQoL. Dashed lines represent the 10% threshold considered to be a clinically relevant change. Error bars represent 95% CIs. HRQoL was scored according to EORTC guidelines, described by mean and standard deviations, and compared between treatment arm using a linear mixed model. EORTC, European Organisation for Research and Treatment of Cancer; HRQoL, health-related quality of life.
FIG A3.
FIG A3.
Schoenfeld's residuals for progression-free survival. (A) Intention-to-treat population. (B) PD-L1–positive population. The solid lines represent a smoothed estimate of beta. The dashed lines represent 95% CIs of this estimate.

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