Prevalence of SWI/SNF genomic alterations in cancer and association with the response to immune checkpoint inhibitors: A systematic review and meta-analysis

Background The association between SWI/SNF genomic alterations and responses to immune checkpoint inhibitors (ICIs) remains conflicting. This meta-analysis was performed to systematically assess the impact of SWI/SNF genomic alterations on response to ICIs in cancer. Methods Relevant studies were searched in multiple databases updated to April 29, 2021. Outcomes of interest included prevalence of SWI/SNF alterations, overall survival (OS), progression-free survival (PFS) and time to treatment failure (TTF). For survival data, the hazard ratio (HR) was adopted, and the effect size was described as 95% confidence intervals (CI). Results 15 studies involving 10,849 patients were included, with the overall frequency of 18.5% in SWI/SNF alterations. Across different cancer types, the mutational frequency of PBRM1 (32.0%) was the highest, followed by ARID1A (18.1%), SMARCA4 (15.6%), SMARCA2 (10.3%), ARID2 (8.1%), SMARCC2 (6.4%) and SMARCB1 (5.0%). Overall analysis showed that SWI/SNF alterations were not associated with improved OS (HR: 0.822, 95 %CI: 0.583–1.158, p = 0.262), PFS (HR: 0.608, 95 %CI: 0.434–1.067, p = 0.094) and TTF (HR: 0.923, 95 %CI: 0.757–1.125, p = 0.427) in patients treated with ICIs. In subgroup analysis, PBRM1 mutations were observed to be linked with improved OS (HR: 0.650, 95 %CI: 0.440–0.960, p = 0.030), PFS (HR: 0.539, 95 %CI: 0.314–0.926, p = 0.025) and TTF (HR: 0.490, 95 %CI: 0.271–0.885, p = 0.018) in RCC patients receiving ICIs. Conclusions The overall prevalence of SWI/SNF alterations was 18.5% across different cancer types. Except for PBRM1 mutations in RCC, SWI/SNF alterations may be uncorrelated with improved clinical outcomes in cancer.