Prognostic value of tumor mutation burden in non-small cell lung cancer: A Meta-Analysis and system review

Background: We performed this meta-analysis to assess the prognostic value of tumor mutation burden (TMB) for patients with non-small cell lung cancer (NSCLC). Methods: Tow authors independently searched the studies in PubMed, web of science, Google Scholar, Cochrane library (from inception to November 2019), according to the key words “non-small cell lung cancer”, “tumor mutation burden”, “prognosis”. The studies were set up according to the inclusion/exclusion criteria. The estimate hazard ratio (HR), odds ratio (OR), risk ratio (RR) and their 95% confidence intervals (95% CIs) were set as effect measures. All analyses were performed by STATA 12.0. Results:28 studies were involved in this meta-analysis, high TMB was associated with good overall survival (OS) (HR=0.53; 95% CI: 0.42-0.67, p<0.001), progression-free survival (PFS) (HR = 0.53; 95% CI: 0.46-0.62, p<0.001), durable clinical benefits (RR = 2.27; 95% CI: 1.79-2.89, P<0.001), and object response rate (RR = 2.27; 95% CI: 1.80-2.85; p<0.001) in patients treated with immune checkpoint inhibits (ICIs). For treated with non-ICIs, poor PFS (HR = 1.62; 95% CI: 1.27-2.07, p<0.001) and OS (HR = 1.56; 95% CI: 1.30-1.87, p=0.001) was found in high TMB. Compared with chemotherapy, ICIs treatment alone had better OS (HR = 0.68; 95% CI: 0.56 to 0.82, p<0.001) and PFS (HR = 0.64; 95% CI: 0.55 to 0.76, p<0.001) for patients with high TMB, however, for low TMB patients, no benefit was found in ICIs treatment. TMB was correlated with EGFR status (OR = 0.28; 95% CI: 0.08- 0.95; p= 0.040), ECOG score (OR = 1.79; 95% CI: 1.09-2.92; p=0.021) and smoking history (OR = 6.01; 95% CI: 1.28 - 28.13; p=0.023). Conclusions: TMB was associated with better survival in cancer patients receiving immunotherapy, and worse survival in cancer patients receiving non-ICIs. Compared with chemotherapy, ICIs was more effective in high TMB patients, but not in low TMB patients.