Clinical Impact of Single Nucleotide Polymorphism in PD-L1 on Response to Nivolumab for Advanced Non-Small-Cell Lung Cancer Patients.
This study was intended to determine the efficacy of nivolumab, we evaluated treatment response with respect to PD-1/PD-L1 SNPs among patients with NSCLC. A total of 50 patients with NSCLC were treated with nivolumab and were also evaluated for PD-1/PD-L1 single nucleotide polymorphisms (SNPs) from plasma DNA. We investigated the association among PD-1/PD-L1 SNPs, objective response rate (ORR) and progression-free survival (PFS). Two of seven SNPs studied showed association with ORR and PFS, with maximum evidence at the marker rs2282055. The ORR was 25%, 15%, 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 = 0.0339 [Cochran-Armitage trend test]). The median PFS time was 2.6 months (95% confidence interval [CI], 1.8 months to 4.3 months) for the G/G and G/T genotypes and 1.8 months (95% confidence interval [CI], 0.4 months to 2.2 months) for the T/T genotype (P = 0.0163). Moreover, the C/C and C/G genotypes of PD-L1 rs4143815 were significantly associated with better ORR and PFS in NSCLC patients treated with nivolumab. These results suggest that rs2282055 and rs4143815 may be a biomarker for the efficacy of nivolumab.
Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan.
Takashi
T
Nomizo
Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan.
Hiroaki
H
Ozasa
Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan.
Takahiro
T
Tsuji
Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan.
Tomoko
T
Funazo
Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan.
Yuto
Y
Yasuda
Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan.
Hironori
H
Yoshida
Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan.
Yoshitaka
Y
Yagi
Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan.
Yuichi
Y
Sakamori
Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan.
Hiroki
H
Nagai
Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan.
Toyohiro
T
Hirai
Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan.
Young Hak
YH
Kim
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D060890:B7-H1 Antigen / Q000235:genetics*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D005260:Female; D005838:Genotype; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D000077594:Nivolumab; D020641:Polymorphism, Single Nucleotide; D061026:Programmed Cell Death 1 Receptor / Q000235:genetics; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D060890:B7-H1 Antigen; C423236:CD274 protein, human; D061026:Programmed Cell Death 1 Receptor; D000077594:Nivolumab