Correlations of switch/sucrose nonfermentable complex mutations with clinical outcomes in advanced non–small cell lung cancer

BACKGROUND: The switch/sucrose nonfermentable complex mutations (SWI/SNF‐mut) are common in non–small cell lung cancer (NSCLC). However, the association of SWI/SNF‐mut with the clinical outcomes of immune checkpoint inhibitors (ICIs), particularly of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR‐TKIs), has not been established. METHODS: We retrospectively collected data of patients at Cancer Hospital Chinese Academy of Medical Sciences. Patients with advanced NSCLC who received programmed cell death protein‐1 or programmed cell death ligand 1 (PD‐[L]1) inhibitors were included in cohort 1 and those with EGFR mutations (EGFR‐mutant) received EGFR‐TKIs monotherapy were included in cohort 2. Two reported Memorial Sloan‐Kettering Cancer Center (MSKCC) cohorts received immunotherapy alone used as the validation for cohort 1. We analyzed the relationship between SWI/SNF alterations and clinical outcomes in each cohort. RESULTS: In total, 1162 patients were included, of which 230 patients (19.8%) were identified as SWI/SNF‐mut with the most common genetic alterations being ARID1A (33.4%) and SMARCA4 (28.3%). In cohort 1 (n = 146), patients with co‐mutations of SWI/SNF and Kirsten rat sarcoma oncogene (KRAS) (SWI/SNFmutKRASmut, n = 18) had significantly prolonged progression‐free survival (PFS) (8.6 m vs. 1.9 m; hazard ratio [HR], 0.31; 95% confidence intervals [CI], 0.11–0.83; p = 0.032) to PD‐(L)1 inhibitors monotherapy, which was consistent with the MSKCC cohorts (not reach [NR] vs. 6.3 m; HR, 0.36, 95% CI, 0.15–0.82; p = 0.016). In cohort 2 (n = 205), ARID1A‐mut (n = 16) was associated with improved PFS after EGFR‐TKIs (20.6 m vs. 11.2 m; HR, 0.47, 95% CI, 0.27–0.94; p = 0.023). CONCLUSIONS: In advanced NSCLC, patients with SWI/SNFmutKRASmut seem to benefit more from ICIs. Furthermore, ARID1A‐mut may provide a protective effect to EGFR‐TKIs in EGFR‐mutant patients. However, this is a retrospective single‐institution analysis that requires further validation by large prospective studies.