Efficacy and toxicity of drugs targeting KRASG12C mutation in non-small cell lung cancer: a meta-analysis

Objective: This study aims to comprehensively assess the effectiveness and safety profiles of medications targeting the KRASG12C mutation in non-small cell lung cancer (NSCLC).

Methods: Relevant studies were systematically identified from PubMed, Embase, Cochrane Library, CNKI, and Wanfang databases up to June 1, 2023. Meta-analysis was conducted to compile and analyze data on efficacy, prognosis, and adverse events (AEs).

Results: Six prospective studies, comprising 563 patients with advanced or metastatic NSCLC, were included in this meta-analysis. Among NSCLC patients, drugs targeting the KRASG12C mutation demonstrated an objective response rate (ORR) of 37% (95% confidence interval [CI] 31-43), a median duration of response (DOR) of 8.89 months (95% CI 7.96-9.83), and a median progression-free survival (PFS) of 6.40 months (95% CI 5.86-6.93). The overall incidence of AEs was 88% (95% CI 79-96), with grade ≥3 AEs occurring in 44% (95% CI 24-64) of cases. Common AEs included diarrhea, nausea, fatigue, and vomiting, with the most frequent grade ≥3 AEs being elevated Alanine transaminase (ALT) or Aspartate transaminase (AST) levels and diarrhea.

Conclusion: Sotorasib, Adagrasib, and Garsorasib are recommended as primary treatment options for patients with KRASG12C mutation NSCLC, demonstrating significant efficacy and manageable safety profiles, particularly in advanced or metastatic settings and as subsequent-line therapies.