CD274 (PD-L1) Polymorphisms as Predictors of Efficacy in First-Line Platinum-Based Chemotherapy for Extensive-Stage Small Cell Lung Cancer

The cornerstone of first-line treatment in extensive-stage small cell lung cancer (ES-SCLC) is platinum- and etoposide-based chemotherapy. Platinum compounds could immunomodulate the tumor microenvironment in addition to their cytotoxic effect. Genetic variation in immune checkpoint (IC) pathways may predict chemotherapy efficacy. Polymorphisms in the IC genes were determined, and their association with survival was analyzed in 78 patients with ES-SCLC treated with chemotherapy. PD-L1 protein expression in tumor tissue was determined. Three variants in <i>CD274</i> were associated with better median progression-free survival (mPFS): rs2297136 (hazard ratio [HR] 0.52, 95% CI 0.29-0.93; <i>p</i> = 0.03), rs2282055 (HR 0.23, 95% CI 0.09-0.64; <i>p</i> = 0.005), and rs822336 (HR 0.41, 95% CI 0.23-0.73; <i>p</i> = 0.002). <i>CTLA4</i> rs231775 was also associated with mPFS (HR 0.30, 95% CI 0.14-0.63; <i>p</i> = 0.002). The variants <i>CD274</i> rs2297136 and <i>CD274</i> rs822336 were associated with platinum sensitivity (odds ratio [OR] 0.13, 95% CI 0.02-0.70; <i>p</i> = 0.02, and OR 0.08, 95% CI 0.01-0.46; <i>p</i> = 0.005, respectively). <i>CD274</i> rs2297136 was also associated with better overall survival (<i>p</i> = 0.02), but not after adjustment for covariates. No association was found between <i>CD274</i> germline variants and PD-L1 tumor expression. Our results suggest that <i>CD274</i> and <i>CTLA4</i> variants may be predictive biomarkers for platinum plus etoposide treatment in ES-SCLC.