Smoking status combined with tumor mutational burden as a prognosis predictor for combination immune checkpoint inhibitor therapy in non‐small cell lung cancer

• Published in: Cancer medicine (Malden, MA) MA), 2021-10, Vol.10 (19), p.6610-6617
• Main Authors: Sun, Li‐Yue, Cen, Wen‐Jian, Tang, Wen‐Ting, Long, Ya‐Kang, Yang, Xin‐Hua, Ji, Xiao‐Meng, Yang, Jiao‐Jiao, Zhang, Ren‐Jing, Wang, Fang, Shao, Jian‐Yong, Du, Zi‐Ming
• Format: Article
• Language: English
• Subjects: Adenocarcinoma; Angiogenesis; Apoptosis; Biomarkers, Tumor - metabolism; Cancer therapies; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - physiopathology; Chemotherapy; Clinical Cancer Research; combination therapy; Female; High-Throughput Nucleotide Sequencing - methods; Humans; immune checkpoint inhibitor; Immune checkpoint inhibitors; Immune Checkpoint Inhibitors - pharmacology; Immune Checkpoint Inhibitors - therapeutic use; Immunotherapy; Immunotherapy - methods; Lung cancer; Lung carcinoma; Lung Neoplasms - drug therapy; Lung Neoplasms - physiopathology; Male; Medical prognosis; Middle Aged; Mutation; Non-small cell lung carcinoma; non‐small cell lung cancer; PD-L1 protein; Prognosis; Retrospective Studies; Small cell lung carcinoma; Smoking; Smoking - adverse effects; Software; Squamous cell carcinoma; Statistical analysis; tumor mutational burden
• ISSN: 2045-7634; 2045-7634
• DOI: 10.1002/cam4.4197

Background This study aimed to explore the prognostic value of tumor mutational burden (TMB) combined with smoking status in advanced non‐small cell lung cancer (NSCLC) patients who received immune checkpoint inhibitor therapy (anti PD‐1/PD‐L1 therapy) combined with chemotherapy or anti‐angiogenesis therapy. Methods We conducted a retrospective analysis of NSCLC patients who underwent next‐generation sequencing test (either 295‐gene panel NGS or 1021‐gene panel NGS) from September 2017 to November 2020. The relationship between TMB and smoking status was investigated. Kaplan–Meier survival analysis was used to compare progression‐free survival (PFS) of the NSCLC patients who received combination immunotherapy grouped by TMB value and smoking status. Results We enrolled 323 cases and 388 cases of NSCLC patients in the 295‐gene panel cohort and 1021‐gene panel cohort, respectively. Positive correlation between TMB and smoking status was found in lung adenocarcinoma, but not in lung squamous cell carcinoma. Participants with both high TMB and smoking status who received immune checkpoint therapy combined with chemotherapy or anti‐angiogenesis therapy had longer PFS than other participants (p