AGO-OVAR 2.29 / ENGOT-ov34 was a randomized, double-blind, placebo-controlled phase III trial designed to evaluate whether adding atezolizumab (anti–PD-L1) to bevacizumab plus non–platinum chemotherapy improves outcomes in patients with recurrent ovarian cancer who were not eligible for platinum-based therapy.
Ovarian Cancer: Symptoms, Causes, Stages, Diagnosis and Treatment
Study Design
The AGO-OVAR 2.29 / ENGOT-ov34 phase III trial enrolled a total of 574 patients with recurrent ovarian cancer between September 2018 and July 2022. Eligible patients included those experiencing a first or second relapse within six months of completing platinum-based chemotherapy, as well as patients with a third relapse regardless of the platinum-free interval, reflecting a population with limited treatment options.
Patients were randomized in a 1:1 ratio to receive either atezolizumab at a dose of 840 mg administered intravenously every two weeks or a matching placebo. In both arms, treatment was given in combination with bevacizumab and the investigator’s choice of non–platinum-based chemotherapy, consisting of either weekly paclitaxel or pegylated liposomal doxorubicin. Study treatment was continued until radiographic disease progression, the occurrence of unacceptable toxicity, or, for atezolizumab or placebo, completion of a maximum treatment duration of two years.
Randomization was stratified according to several clinically relevant factors, including the number of prior lines of therapy, the selected chemotherapy backbone, previous exposure to bevacizumab, and tumor PD-L1 expression status. PD-L1 testing was performed centrally using the VENTANA SP142 immunohistochemistry assay on recent tumor biopsy specimens, ensuring standardized biomarker assessment across the study population.
Patient Characteristics
- 72% had prior exposure to bevacizumab
- 36% had received three prior lines of therapy
- 26% had PD-L1–positive tumors
- 54% received weekly paclitaxel as chemotherapy backbone
This reflects a heavily pretreated and clinically challenging population.
Efficacy Results
Overall Survival
In the final overall survival analysis, conducted after 418 deaths, the addition of atezolizumab did not result in a statistically significant improvement in overall survival. Median overall survival was 14.2 months in the atezolizumab arm compared with 13.0 months in the placebo arm. This corresponded to a hazard ratio of 0.83 (95% CI, 0.68–1.01; P = 0.06). Although the predefined threshold for statistical significance was not met, a numerical trend toward improved survival was observed in favor of atezolizumab.
Progression-Free Survival
Progression-free survival results similarly failed to demonstrate a meaningful benefit with the addition of atezolizumab. Median PFS was 6.4 months in the atezolizumab group and 6.7 months in the placebo group, yielding a hazard ratio of 0.87 (95% CI, 0.73–1.04; P = 0.12). These findings indicate no significant improvement in disease control with atezolizumab in this treatment setting.
Biomarker Analysis
Exploratory biomarker analyses showed that PD-L1 expression did not modify the treatment effect. Overall survival outcomes were similar regardless of PD-L1 status, and PD-L1 expression failed to identify any subgroup that derived a clinically meaningful benefit from atezolizumab.
Safety
Grade ≥3 adverse events occurred in:
- 72% of patients receiving atezolizumab
- 69% of patients receiving placebo
The safety profile was consistent with known toxicities of atezolizumab, bevacizumab, and chemotherapy.
Key Conclusion
The addition of atezolizumab to bevacizumab and non–platinum chemotherapy did not significantly improve overall survival or progression-free survival in patients with recurrent ovarian cancer who were platinum-ineligible. Despite a numerical OS trend, the results were not statistically significant, and PD-L1 status did not predict benefit. Overall, the safety profile remained manageable and aligned with prior experience.