Abstract 2604: PD-L1 rs2282055 is associated with opposite treatment effect between platinum-based chemotherapy and nivolumab treatment
Authors: Takashi Nomizo, Hiroaki Ozasa, Takahiro Tsuji, Tomoko Funazo, Yuto Yasuda, Hironori Yoshida, Yuichi Sakamori, Toyohiro Hirai, Yong Hak Kim
Journal: Cancer Research (2018)

Abstract Treatment of lung cancer is improved recently, especially immune-check point inhibitors prolong progression-free survival (PFS) and overall survival (OS), however, Lung cancer is still leading cause of death worldwide. This is because of response rates in the treatment of non-small cell lung cancer (NSCLC) with combination platinum-based chemotherapy vary from 20% to 40%, and response rates of the treatment of NSCLC with nivolumab is around 20%, whereas with leaving a large number of patients with either stable or progressive disease. It is currently difficult to predict treatment response to chemotherapy and nivolumab since there are no precise biomarkers for it. Recently, we have reported that PD-L1 single nucleotide polymorphisms (SNPs) are associated with response to nivolumab treatment. This study was intended to determine the efficacy of platinum-based combination chemotherapy either in a doublet or triplet, and nivolumab treatment respect to PD-L1 SNPs among patients with NSCLC. A total of 139 patients with NSCLC were treated with platinum-based doublet or triplet chemotherapy, 73 patients treated with nivolumab and were also evaluated for PD-L1 SNPs from plasma DNA. We investigated the association among PD-L1 SNPs, objective response rate (ORR) and PFS. PD-L1 rs2282055 was associated with ORR and PFS in the patients treated with pulatinum-based chemotherapy and nivolumab. In the patients treated with nivolumab, the ORR was 24%, 12%, and 0% for the G/G, G/T and T/T genotypes of PD-L1 rs2282055, respectively. The G allele of PD-L1 rs2282055 was significantly associated with better clinical response compared with the T allele (P = 0.0056 [Cochran-Armitage trend test]). The median PFS time was 2.1 months (95% confidence interval [CI], 1.8 months to 3.9 months) for the G/G and G/T genotypes and 2.2 months (95% confidence interval [CI], 0.9 months to 2.6 months) for the T/T genotype (P = 0.0210). On the other hand, The T allele of PD-L1 rs2282055 was significantly associated with better clinical response compared with the G allele in the patients treated with platinum-based combination chemotherapy either in a doublet or triplet (P = 0.0080 [Cochran-Armitage trend test]). The median PFS time was 11.0 months (95% confidence interval [CI], 6.2 months to 16.3 months) for the T/T genotypes and 7.3 months (95% confidence interval [CI], 6.0 months to 8.2 months) for the G/T and G/G genotype (P = 0.0284). In conclusion, these results suggest that the T/T genotype of PD-L1 SNP rs2282055 associated with the better treatment effect of platinum-based combination chemotherapy, on the contrary, the T/T of rs2282055 negatively associated with response to nivolumab treatment. It might be used as a biomaker for selection of the regimen of NSCLC treatment. Citation Format: Takashi Nomizo, Hiroaki Ozasa, Takahiro Tsuji, Tomoko Funazo, Yuto Yasuda, Hironori Yoshida, Yuichi Sakamori, Toyohiro Hirai, Yong Hak Kim. PD-L1 rs2282055 is associated with opposite treatment effect between platinum-based chemotherapy and nivolumab treatment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2604.