Eight cohorts of five RCTs for a total of 3848 patients with available TMB data evaluated first-line IO regimens containing anti-PD-1 (nivolumab or pembrolizumab) or anti-PD-L1 (atezolizumab or durvalumab) agents in association or not with anti-CTLA-4 (ipilimumab or tremelimumab) agents compared with standard platinum-based CT in unresectable or advanced non-oncogene-addicted NSCLC. This evidence concerns the gene CTLA4 and non-small cell lung carcinoma.