Adding Atezolizumab to Chemo/Bevacizumab May Not Be Beneficial in Ovarian Cancer

Adding Atezolizumab to Chemo/Bevacizumab May Not Be Beneficial in Ovarian Cancer

Adding atezolizumab (Tecentriq) to single-agent non–platinum-based chemotherapy and bevacizumab (Avastin) for patients with recurrent ovarian cancer did not provide any additional benefits, according to the final analysis of the phase 3 AGO-OVAR 2.29/ENGOT-ov34 study (NCT03353831) presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting.

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, from the AGO Study Group & Medical Faculty at Mannheim, Heidelberg University, 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