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

TL;DR

This study finds that genetic variations in CD274 and CTLA4 genes may predict how well patients with extensive-stage small cell lung cancer respond to first-line chemotherapy.

Contribution

The study identifies specific CD274 and CTLA4 polymorphisms as potential predictive biomarkers for chemotherapy efficacy in extensive-stage small cell lung cancer.

Findings

Three CD274 polymorphisms (rs2297136, rs2282055, rs822336) and one CTLA4 polymorphism (rs231775) were associated with improved progression-free survival.

CD274 rs2297136 and rs822336 were linked to increased platinum sensitivity in patients.

CD274 rs2297136 was associated with better overall survival, though not significant after adjusting for covariates.

Abstract

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 CD274 were associated with better median progression-free survival (mPFS): rs2297136 (hazard ratio [HR] 0.52, 95% CI 0.29–0.93; p = 0.03), rs2282055 (HR 0.23, 95% CI 0.09–0.64; p = 0.005), and rs822336 (HR 0.41, 95% CI 0.23–0.73; p = 0.002). CTLA4 rs231775 was also associated with mPFS (HR 0.30, 95% CI 0.14–0.63; p = 0.002). The variants CD274 rs2297136 and CD274 rs822336 were associated with platinum sensitivity (odds ratio [OR] 0.13, 95% CI 0.02–0.70; p = 0.02, and OR 0.08, 95% CI 0.01–0.46; p = 0.005, respectively). CD274 rs2297136 was also associated with better overall survival (p = 0.02), but not after adjustment for covariates. No association was found between CD274 germline variants and PD-L1 tumor expression. Our results suggest that CD274 and CTLA4 variants may be predictive biomarkers for platinum plus etoposide treatment in ES-SCLC.

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