Clinical Impact of Single Nucleotide Polymorphism in PD-L1 on Response to Nivolumab for Advanced Non-Small-Cell Lung Cancer Patients

Overview

Journal Sci Rep

Specialty Science

Date 2017 Mar 24

PMID 28332580

Citations 40

Authors

Takashi Nomizo

Hiroaki Ozasa

Takahiro Tsuji

Tomoko Funazo

Yuto Yasuda

Hironori Yoshida

Yoshitaka Yagi

Yuichi Sakamori

Hiroki Nagai

Toyohiro Hirai

Young Hak Kim

Affiliations

Soon will be listed here.

Abstract

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.

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References

Borghaei H, Paz-Ares L, Horn L, Spigel D, Steins M, Ready N . Nivolumab versus Docetaxel in Advanced Nonsquamous Non-Small-Cell Lung Cancer. N Engl J Med. 2015; 373(17):1627-39. PMC: 5705936. DOI: 10.1056/NEJMoa1507643. View

Herbst R, Soria J, Kowanetz M, Fine G, Hamid O, Gordon M . Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients. Nature. 2014; 515(7528):563-7. PMC: 4836193. DOI: 10.1038/nature14011. View

Savabkar S, Azimzadeh P, Chaleshi V, Nazemalhosseini Mojarad E, Aghdaei H . Programmed death-1 gene polymorphism (PD-1.5 C/T) is associated with gastric cancer. Gastroenterol Hepatol Bed Bench. 2014; 6(4):178-82. PMC: 4017527. View

Abdel-Rahman O . Correlation between PD-L1 expression and outcome of NSCLC patients treated with anti-PD-1/PD-L1 agents: A meta-analysis. Crit Rev Oncol Hematol. 2016; 101:75-85. DOI: 10.1016/j.critrevonc.2016.03.007. View

Gainor J, Shaw A, Sequist L, Fu X, Azzoli C, Piotrowska Z . EGFR Mutations and ALK Rearrangements Are Associated with Low Response Rates to PD-1 Pathway Blockade in Non-Small Cell Lung Cancer: A Retrospective Analysis. Clin Cancer Res. 2016; 22(18):4585-93. PMC: 5026567. DOI: 10.1158/1078-0432.CCR-15-3101. View

Nicolazzo C, Raimondi C, Mancini M, Caponnetto S, Gradilone A, Gandini O . Monitoring PD-L1 positive circulating tumor cells in non-small cell lung cancer patients treated with the PD-1 inhibitor Nivolumab. Sci Rep. 2016; 6:31726. PMC: 4995431. DOI: 10.1038/srep31726. View

Lee S, Jung D, Choi J, Jin C, Hong M, Do S . PD-L1 polymorphism can predict clinical outcomes of non-small cell lung cancer patients treated with first-line paclitaxel-cisplatin chemotherapy. Sci Rep. 2016; 6:25952. PMC: 4867646. DOI: 10.1038/srep25952. View

Gettinger S, Horn L, Gandhi L, Spigel D, Antonia S, Rizvi N . Overall Survival and Long-Term Safety of Nivolumab (Anti-Programmed Death 1 Antibody, BMS-936558, ONO-4538) in Patients With Previously Treated Advanced Non-Small-Cell Lung Cancer. J Clin Oncol. 2015; 33(18):2004-12. PMC: 4672027. DOI: 10.1200/JCO.2014.58.3708. View

Isla D, Sarries C, Rosell R, Alonso G, Domine M, Taron M . Single nucleotide polymorphisms and outcome in docetaxel-cisplatin-treated advanced non-small-cell lung cancer. Ann Oncol. 2004; 15(8):1194-203. DOI: 10.1093/annonc/mdh319. View

10.

Champiat S, Ferte C, Lebel-Binay S, Eggermont A, Soria J . Exomics and immunogenics: Bridging mutational load and immune checkpoints efficacy. Oncoimmunology. 2014; 3(1):e27817. PMC: 3937193. DOI: 10.4161/onci.27817. View

11.

Tumeh P, Harview C, Yearley J, Shintaku I, Taylor E, Robert L . PD-1 blockade induces responses by inhibiting adaptive immune resistance. Nature. 2014; 515(7528):568-71. PMC: 4246418. DOI: 10.1038/nature13954. View

12.

Pizarro C, Garcia-Diaz D, Codner E, Salas-Perez F, Carrasco E, Perez-Bravo F . PD-L1 gene polymorphisms and low serum level of PD-L1 protein are associated to type 1 diabetes in Chile. Diabetes Metab Res Rev. 2014; 30(8):761-6. DOI: 10.1002/dmrr.2552. View

13.

Akbay E, Koyama S, Carretero J, Altabef A, Tchaicha J, Christensen C . Activation of the PD-1 pathway contributes to immune escape in EGFR-driven lung tumors. Cancer Discov. 2013; 3(12):1355-63. PMC: 3864135. DOI: 10.1158/2159-8290.CD-13-0310. View

14.

Abelson A, Johansson C, Kozyrev S, Kristjansdottir H, Gunnarsson I, Svenungsson E . No evidence of association between genetic variants of the PDCD1 ligands and SLE. Genes Immun. 2006; 8(1):69-74. DOI: 10.1038/sj.gene.6364360. View

15.

Chae Y, Pan A, Davis A, Raparia K, Mohindra N, Matsangou M . Biomarkers for PD-1/PD-L1 Blockade Therapy in Non-Small-cell Lung Cancer: Is PD-L1 Expression a Good Marker for Patient Selection?. Clin Lung Cancer. 2016; 17(5):350-361. DOI: 10.1016/j.cllc.2016.03.011. View

16.

Chen D, Irving B, Hodi F . Molecular pathways: next-generation immunotherapy--inhibiting programmed death-ligand 1 and programmed death-1. Clin Cancer Res. 2012; 18(24):6580-7. DOI: 10.1158/1078-0432.CCR-12-1362. View

17.

Postow M, Chesney J, Pavlick A, Robert C, Grossmann K, McDermott D . Nivolumab and ipilimumab versus ipilimumab in untreated melanoma. N Engl J Med. 2015; 372(21):2006-17. PMC: 5744258. DOI: 10.1056/NEJMoa1414428. View

18.

Lin T . Ofatumumab: a novel monoclonal anti-CD20 antibody. Pharmgenomics Pers Med. 2012; 3:51-9. PMC: 3513208. DOI: 10.2147/pgpm.s6840. View

19.

Oko A, Wyrwicz L, Glyda M, Idasiak-Piechocka I, Binczak-Kuleta A, Kaczmarczyk M . CD52 gene polymorphism and its potential effect on the response to alemtuzumab in renal transplant recipients. Ann Acad Med Stetin. 2010; 55(2):22-6. View

20.

Fabris M, Quartuccio L, Lombardi S, Saracco M, Atzeni F, Carletto A . The CC homozygosis of the -174G>C IL-6 polymorphism predicts a lower efficacy of rituximab therapy in rheumatoid arthritis. Autoimmun Rev. 2010; 11(5):315-20. DOI: 10.1016/j.autrev.2010.06.012. View