Predictive value of tumor mutational burden for immunotherapy in non-small cell lung cancer: A systematic review and meta-analysis

Background Immunotherapy has emerged as a promising treatment for non-small cell lung cancer (NSCLC). Yet, some patients cannot benefit from immunotherapy, and reliable biomarkers for selecting sensitive patients are needed. Herein, we performed a meta-analysis to evaluate the predictive value of tumor mutational burden (TMB) in NSCLC patients treated with immunotherapy. Methods Eligible studies were comprehensively searched from electronic databases prior to August 31, 2021. Meta-analyses of high TMB versus low TMB as well as immunotherapy versus chemotherapy in patients with high/low TMB were conducted. Hazard ratio (HR) with corresponding 95% confidence interval (95%CI) for progression-free survival (PFS) and overall survival (OS) and odds ratio (OR) with 95%CI for objective response rate (ORR) were calculated. Results A total of 31 datasets (3437 patients) and 6 randomized controlled trials (3662 patients) were available for meta-analyses of high TMB versus low TMB and immunotherapy versus chemotherapy, respectively. High TMB predicted significantly favorable PFS (HR = 0.54, 95%CI: 0.46-0.63, P<0.001) and OS (HR = 0.70, 95%CI: 0.57-0.87, P = 0.001), and higher ORR (OR = 3.14, 95%CI: 2.28-4.34, P<0.001) compared with low TMB. In patients with high TMB, immunotherapy was associated with improved PFS (HR = 0.62, 95%CI: 0.53-0.72), OS (HR = 0.67, 95%CI: 0.57-0.79) and ORR (OR = 2.35, 95%CI: 1.74-3.18) when compared with chemotherapy. However, in patients with low TMB, immunotherapy seemed to predict inferior PFS (HR = 1.20, 95%CI: 1.02-1.41) and ORR (OR = 0.61, 95%CI: 0.44-0.84) and have no OS benefit (HR = 0.88, 95%CI: 0.74-1.05) as compared with chemotherapy. Conclusion This meta-analysis demonstrates more clinical benefits concerning treatment response and survival outcomes in high-TMB NSCLC patients who are treated with immunotherapy. TMB is a promising biomarker for discriminating NSCLC patients who can benefit more from immunotherapy.

Automated summary

This meta-analysis demonstrates that high-TMB NSCLC patients treated with immunotherapy have more clinical benefits in terms of treatment response and survival outcomes. TMB is a promising biomarker for selecting NSCLC patients who can benefit more from immunotherapy.