The predictive value of BRCA mutation on survival of cancer patients treated with immune checkpoint inhibitors: A systematic review and meta-analysis of phase III randomized clinical trials.

Abstract

2594 Background: Immune checkpoint inhibitors (ICIs) have significantly enhanced survival for various types of cancers; however, resistance has limited the number of patients who can benefit from these regimens. Therefore, additional biomarkers are necessary to hopefully overcome resistance. Currently, the role of BRCA Mutation in ICI therapy remains poorly understood and controversial. Methods: We systematically searched PubMed, Web of Science, and Cochrane for phase III randomized clinical trials (RCTs) comparing ICI with placebo or standard-of-care cancer treatment stratified by BRCA mutation status as wildtype or mutant type up to 19 November 2024 regardless of cancer type or stage. The included phase III trials must report at least one of the following: Progression-free survival (PFS) or overall survival (OS); the meta-analysis was conducted using RevMan 5.4 pooling hazard ratio (HR) with 95% confidence intervals (CI) with a p-value of < 0.05 considered significant. Results: We conducted a meta-analysis of six phase III RCTs involving 3,328 patients: three trials investigated ovarian cancer, two investigated prostate cancer, and one investigated breast cancer. The analysis revealed that ICIs significantly improved both OS and PFS for patients with BRCA mutation, with HR of 0.61 (95% CI, 0.46 – 0.81, p = 0.0008) and 0.64 (95% CI, 0.47 – 0.89, p = 0.008), respectively. Furthermore, for patients with wildtype BRCA, the analysis revealed that using ICIs significantly improves PFS with HR of 0.81 (95% CI, 0.72 – 0.90, p = 0.0001). However, ICIs did not significantly improve overall survival, with HR of 0.94 (95% CI, 0.84 – 1.06, p = 0.33). Conclusions: The use of ICIs in cancer patients with BRCA mutation is associated with significant improvement in PFS and OS; however, in patients with wildtype BRCA, the use of ICIs showed only significant improvement in PFS with no significant improvement in OS.