Prognostic value of KRAS mutation in advanced non-small-cell lung cancer treated with immune checkpoint inhibitors: A meta-analysis and review

Abstract

Immune checkpoint inhibitors (ICIs) have emerged as a promising treatment option in the fight against advanced non-small-cell lung cancer (NSCLC). KRAS is the most frequently mutated oncogene in NSCLC. We performed this meta-analysis to investigate if KRAS mutation status affects survival benefits of ICIs in patients with advanced NSCLC. Electronic databases were searched for eligible studies. We included randomized trials with the data of overall survival stratified by KRAS mutation status. From 3 eligible studies, 138 patients with KRAS mutant NSCLC and 371 with KRAS wild-type tumor were included in the meta-analysis. Compared to chemotherapy with docetaxel, ICIs improved overall survival in patients with previously treated KRAS mutant NSCLC (hazard ratio = 0.64 [95% confidence interval, 0.43–0.96], P = 0.03). For patients with KRAS wild-type NSCLC, however, ICIs did not prolong overall survival over that with chemotherapy (hazard ratio = 0.88 [95% confidence interval, 0.68–1.13], P = 0.30). In conclusion, ICIs as a salvage therapy improved overall survival over that with docetaxel in advanced NSCLC patients with KRAS mutation, but not in those with KRAS wild-type tumor. These results suggest that KRAS mutation status may be a potential biomarker for survival benefits to ICIs.