Addition of Atezolizumab to Chemotherapy and Bevacizumab Does Not Yield Benefit in Ovarian Cancer

Frederik Marmé, MD, PhD

There were no additional benefits observed when atezolizumab (Tecentriq) was added to treatment with single-agent non–platinum-based chemotherapy and bevacizumab (Avastin) for patients with recurrent ovarian cancer, according to the final analysis of the phase 3 AGO-OVAR 2.29/ENGOT-ov34 study (NCT03353831).

Findings presented at the 2024 ASCO Annual Meeting revealed that the median progression-free survival (PFS) was 6.4 months (95% CI, 6.1-7.5) with the addition of atezolizumab to chemotherapy and bevacizumab compared with a median of 6.7 months (95% CI, 6.2-8.1) with placebo plus chemotherapy and bevacizumab (HR, 0.87; 95% CI, 0.73-1.04; P = .12). The median overall survival (OS) was 14.2 months (95% CI, 13.0-16.1) with the atezolizumab combination compared with 13.0 months (95% CI, 11.9-15.1) with placebo (HR, 0.83; 95% CI, 0.68-1.01; P = .06). An improvement in outcomes was also not observed in those with PD-L1–positive disease, although a hypothesis generating improvement was seen in patients who received prior bevacizumab and those who received paclitaxel.

"The addition of atezolizumab to single-agent non–platinum-based chemotherapy in combination with bevacizumab did not significantly improve OS or PFS," lead investigator Frederik Marmé, MD, PhD, an assistant professor of Gynecology for the Medical Faculty of Heidelberg at the University of Heidelberg in Germany, said during a presentation of the results. "Response rates were similar between treatment arms with a numerically longer duration of response in patients receiving atezolizumab. Results were independent of PD-L1 status in a recent biopsy using the SP142 assay."

In the study, 574 patients were randomly assigned 1:1 between atezolizumab at 840 mg every 2 weeks (n = 285) or matched placebo (n = 289). In both arms, patients received bevacizumab at 10 mg/kg every 2 weeks and either weekly paclitaxel at 80 mg/m² in a 28-day cycle or pegylated liposomal doxorubicin (PLD) at 40 mg/m² on day 1 of a 28-day cycle.

The median age of patients was 62 years, and patients had an ECOG performance status of 0 (54.9%) or 1 (44.6%). The most common histology was high-grade serous (72.6%) and 36.4% had received 3 prior lines of therapy, with 63.6% receiving 1 to 2 prior lines. The planned chemotherapy was mixed between PLD (46.0%) and paclitaxel (54.0%). Nearly three-fourths of patients had received prior bevacizumab before entering the study (72.5%).

At randomization, PD-L1 status showed that nearly two-thirds of patients were negative for the biomarker. The testing was completed using the VENTANA SP142 assay. Marmé noted that testing was completed on tissue that was no more than 3 months old. PD-L1 testing was not initially considered in the trial as a stratification factor but was added later at an amendment. The overall results from the testing showed that 25.8% were PD-L1–positive, 64.6% tested negative, and 9.6% were labeled as non-informative.

The objective response rate (ORR) in the atezolizumab arm was 39.6% (95% CI, 33.6%-45.6%), with 4.3% of patients experiencing a complete response (CR) and 35.3% having a partial response (PR). In the placebo arm, the ORR was 43.5% (95% CI, 37.4%-49.7%) with 2.4% having a CR and 41.1% having a PR. The median duration of response with atezolizumab was 8.6 months (95% CI, 6.9-10.4) compared with 6.1 months (95% CI, 5.3-7.2) in the placebo group.

In a post-hoc exploratory analysis, those treated with prior bevacizumab (n = 416) saw signs of improvement in OS with the addition of atezolizumab. In this group of patients, the median OS was 14.9 months (95% CI, 13.3-18.8) with atezolizumab compared with 12.6 months (95% CI, 11.6-14.4) with placebo (HR, 0.74; 95% CI, 0.59-0.93). In patients receiving paclitaxel (n = 310), the median OS was 16.2 months (95% CI, 13.9-20.8) with the addition of atezolizumab compared with 14.3 months (95% CI, 12.3-15.9) with placebo (HR, 0.75; 95% CI, 0.57-0.98).

"These results remain hypothesis generating," Marmé cautioned.

Treatment-emergent adverse events (AEs) were experienced by most patients, with grade 3 or higher events in 71.5% of those in the atezolizumab arm and 68.9% in the placebo group. Serious AEs were seen in 63.7% of those in the atezolizumab arm and 51.4% in the placebo group. AEs of special interest occurred in 18.5% of those in the atezolizumab arm and 8.0% of those in the placebo group. Bevacizumab-related AEs of special interest were similar between groups at 6.8% in the investigational group and 5.2% in the placebo arm. AEs led to the discontinuation of the study drug or placebo for 16.4% of those in the atezolizumab group and 14.3% in the placebo arm.

The most common grade 3 or higher AEs in the atezolizumab arm and placebo arms, respectively, were neutropenia (16.0% vs 11.9%), hypertension (10.7% vs 9.8%), anemia (8.2% vs 3.5%), gastrointestinal obstruction (7.8% vs 8.4%), and fatigue (7.1% vs 5.6%). Grade 3 or higher immune-mediate AEs were seen in 12.5% of patients in the atezolizumab group compared with 5.9% in the placebo arm, with the most common being pancreatitis (3.9% and 1.4%).

"Safety findings were consistent with the known toxicity profiles of the investigated agents," said Marmé. "Exploratory analyses including stool microbiome, tumor microenvironment, cDNA, and alternative PD-L1 analyses are ongoing."

Reference

Marmé F, Harter P, Redondo A, et al. Atezolizumab versus placebo in combination with bevacizumab and non-platinum-based chemotherapy in recurrent ovarian cancer: final overall and progression-free survival results from the AGO-OVAR 2.29/ENGOT-ov34 study. J Clin Oncol. 2024;42 (suppl 17):LBA5501. doi: 10.1200/JCO.2024.42.17_suppl.LBA5501