The Efficacy of Immune Checkpoint Inhibitors vs. Chemotherapy for KRAS-Mutant or EGFR-Mutant Non-Small-Cell Lung Cancers: A Meta-Analysis Based on Randomized Controlled Trials

OBJECTIVE: To assess and compare the effectiveness of immune checkpoint inhibitors vs. chemotherapy for KRAS-mutant or EGFR-mutant non-small-cell lung cancers. METHODS: Until February 19, 2022, Cochrane Library, PubMed, Web of Science, and Embase were searched for relevant randomized controlled trials (RCTs) in NSCLC. Progression-free survival (PFS) and overall survival (OS) were used as outcome measures. The studies were conducted using the Cochrane methodology for meta-analyses, and all statistical analyses were made with Review Manager Software (RevMan version 5.4). RESULTS: Our meta-analysis included nine clinical trials including 5633 participants with NSCLC. Immune checkpoint drugs extended OS (hazard ratio (HR), 0.67; 95% confidence interval (CI), 0.60–0.76) and PFS (HR, 0.44; 95% CI, 0.35-0.56) in patients with EGFR wild-type compared to chemotherapy alone, whereas programmed cell death 1 ligand 1 (PD-L1)/programmed cell death-1 (PD-1) inhibitors with chemotherapy versus chemotherapy extended PFS in NSCLC patients with EGFR mutations (HR, 0.63; 95% CI, 0.42-0.94). Meanwhile, immune checkpoint inhibitors vs. chemotherapy improved the OS (HR, 0.65; 95% CI, 0.48–0.88) and PFS (HR, 0.49; 95% CI, 0.36–0.66) of NSCLC patients with KRAS mutation. NSCLCs with KRAS G12C mutation had a much better PFS with ICIs than with chemotherapy (HR, 0.38; 95% CI, 0.21–0.71). CONCLUSION: This research revealed that individuals with EGFR wild-type NSCLC or KRAS mutation may benefit from PD-L1/PD-1 inhibitors and that PD-L1/PD-1 inhibitors in combination with chemotherapy seem to be more successful than chemotherapy alone in NSCLC patients with EGFR mutation.