Single nucleotide polymorphisms in PD-L1 and outcome in nivolumab-treated advanced non-small-cell lung cancer patients

Abstract

Background: Nivolumab is an established agent in the management of non-small-cell lung cancer (NSCLC); however, while some patients with lung cancer have marked responses to nivolumab, others do not respond. To determine the efficacy of nivolumab, we retrospectively evaluated treatment response with respect to PD-1/PD-L1 SNPs among patients with NSCLC. Methods: Between December 2015 and October 2016, a total of 68 patients with histologically or cytologically confirmed NSCLC were treated with nivolumab. Among these 68 patients, all of whom were registered at Kyoto University Hospital. Genomic DNA was extracted from peripheral blood and genotyping was performed using real-time PCR method. We investigated the possible correlation of PD-1/PD-L1 SNPs with PFS (progression-free survival) using Kaplan-Meier method. Results: A total of 68 patients were evaluated for clinical response. The G allele of PDL1 rs2282055 was significantly associated with better clinical response. The median PFS time was 4.2 months (95% confidence interval [CI], 1.7 months to 3.9 months) for the G/G and G/T genotypes of rs2282055 and 2.0 months (95% confidence interval [CI], 0.9 months to 2.2 months) for the T/T genotype (P=0.0388). Moreover, the T/T and C/T genotypes of PD-L1 rs1411262 were significantly associated with better PFS in NSCLC patients treated with nivolumab. Conclusions: The G/G and G/T genotypes of PD-L1 rs2282055 were significantly associated with better ORR and PFS in NSCLC patients treated with nivolumab. These results suggest that PD-L1 SNPs may be a biomarker for the efficacy of nivolumab.