No Benefit With Atezolizumab in BRCA1/2-Mutant or HRD Ovarian Cancer

New research suggests that adding atezolizumab to standard treatment does not improve progression-free survival (PFS) in patients with advanced ovarian cancer and BRCA1/2 mutations or homologous recombination deficiency (HRD).¹

Previous results from the IMagyn050 trial showed that atezolizumab did not improve PFS in the overall cohort of patients with stage III-IV ovarian cancer.² 

In a biomarker analysis, researchers found no PFS benefit with atezolizumab among patients with HRD or BRCA1/2 mutations.¹ Results from this analysis were published in Clinical Cancer Research.

The IMagyn050 trial (ClinicalTrials.gov Identifier: NCT03038100) included 1301 patients with stage III-IV ovarian cancer. They were randomly assigned to receive either atezolizumab (n=651) or placebo (n=650) every 3 weeks for 22 cycles, in combination with carboplatin plus paclitaxel in cycles 1-6 and bevacizumab every 3 weeks for 22 cycles.

For this exploratory analysis, next-generation sequencing was used in 1050 patient samples — 537 in the atezolizumab arm and 513 in the placebo arm. BRCA1/2 mutations were present in 22% of patients in each arm. HRD was present in 45% of patients in the atezolizumab arm and 46% of patients in the placebo arm.

There was no association between outcomes of atezolizumab and BRCA1/2 mutation status or homologous recombination status. However, the median PFS was longer among patients with BRCA1/2-mutated tumors and those with HRD in both treatment arms. 

In the control arm, the median PFS was 21.1 months in the BRCA1/2-mutated group and 16.7 months in the non-mutated group (hazard ratio [HR], 0.62; 95% CI, 0.46-0.84). In the atezolizumab arm, the median PFS was 21.9 months in the BRCA1/2-mutated group and 18.7 months in the non-mutated group (HR, 0.67; 95% CI, 0.49-0.91). 

In the control arm, the median PFS was 20.7 months in the HRD group and 15.3 months in the homologous recombination proficient (HRP) group (HR, 0.63; 95% CI, 0.49-0.80). In the atezolizumab arm, the median PFS was 20.7 months in the HRD group and 18.0 months in the HRP group (HR, 0.73; 95% CI, 0.57-0.94).

“Neither BRCA1/2 mutation nor HRD predicted enhanced benefit from atezolizumab,” the researchers wrote. “This is the first randomized double-blind trial in ovarian cancer demonstrating that genomic instability triggered by BRCA1/2 mutation or HRD is not associated with improved sensitivity to immune checkpoint inhibitors.”

Disclosures: This research was supported by F. Hoffmann-La Roche/Genentech. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

Reference

Landen CN, Molinero L, Hamidi H, et al. Influence of genomic landscape on cancer immunotherapy for newly diagnosed ovarian cancer: Biomarker analyses from the IMagyn050 randomized clinical trial. Clin Cancer Res. Published online May 1, 2023. doi:10.1158/1078-0432.CCR-22-2032

This article originally appeared on Cancer Therapy Advisor