Tumor Mutation Burden as a Potential Biomarker for PD-1/PD-L1 Inhibition in Advanced Non-small Cell Lung Cancer

• Published in: Targeted oncology Vol. 15; no. 1; pp. 93 - 100
• Main Authors: Huang, Di, Zhang, Fan, Tao, Haitao, Zhang, Sujie, Ma, Junxun, Wang, Jinliang, Liu, Zhefeng, Cui, Pengfei, Chen, Shixue, Huang, Ziwei, Wu, Zhaozhen, Zhao, Lei, Hu, Yi
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01.02.2020; Springer Nature B.V
• Subjects: Adult; Aged; Aged, 80 and over; Apoptosis; Biomarkers; Biomarkers, Tumor - metabolism; Biomedicine; Cancer therapies; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - pathology; Chemotherapy; Deoxyribonucleic acid; DNA; FDA approval; Female; Hospitals; Humans; Immunotherapy - methods; Ligands; Lung cancer; Lung Neoplasms - drug therapy; Lung Neoplasms - pathology; Male; Medicine; Medicine & Public Health; Middle Aged; Mutation; Oncology; Original Research Article; Patients; Programmed Cell Death 1 Receptor - antagonists & inhibitors; Proteins
• ISSN: 1776-2596; 1776-260X
• DOI: 10.1007/s11523-020-00703-3

Background Immunotherapy based on programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors has revolutionized the treatment of non-small cell lung cancer (NSCLC). Patients with high PD-L1 expression or DNA mismatch repair deficiency (dMMR)/microsatellite instability-high (MSI-H) cancer are reported to benefit from PD-1/PD-L1 inhibitors. However, additional biomarkers are needed, and whether tumor mutation burden (TMB) can be a robust biomarker or not is still controversial. Objective We conducted this study to assess TMB as a biomarker for PD-1/PD-L1 inhibitor treatment in advanced NSCLC patients in a real-world setting. Patients and Methods Chinese NSCLC patients who received a PD-1/PD-L1 inhibitor at the People’s Liberation Army General Hospital and who had pathological tissues available for TMB were retrospectively analyzed. Demographic and clinical information were evaluated. Targeted next-generation sequencing (NGS) of the tumor tissue was performed. The relationship between TMB and clinical benefit was assessed. Results Thirty-four patients treated with PD-1/PD-L1 inhibitors between March 2015 and January 2019 were analyzed. The TMB was greater in patients with complete response (CR)/partial response (PR) versus stable disease (SD) versus progressive disease (PD) (median 11 vs. 9.7 vs. 4.2 mutations/megabase [Mb]; p  = 0.049). The median progression-free survival was 10.6 months in the TMB-high group versus 3.9 months in the TMB-low group (cut-off value = 10 mutations/Mb) (hazard ratio [HR] 0.26 [95% confidence interval 0.12–0.57], p  = 0.0007). The median overall survival was 21.0 months and 11.6 months (HR 0.37 [0.17–0.81], p  = 0.0126) in the TMB-high group and the TMB-low group, respectively. The disease control rate was higher in the TMB-high group than in the TMB-low group (100% vs. 70%, p  = 0.024). Conclusions High TMB was associated with a better outcome in advanced NSCLC patients who received PD-1/PD-L1 inhibitors in China. Further studies are needed to confirm our findings.