The efficacy of first-line chemotherapy is associated with KRAS mutation status in patients with advanced non-small cell lung cancer: a meta-analysis

Non-small cell lung cancer (NSCLC) patients harboring KRAS mutation were associated with worse prognosis and lower response to epidermal growth factor receptor (EGFR) target therapy than those with wild-type tumors. However, whether the underlying biological differences are associated with the efficacy of cytotoxic chemotherapy in advanced NSCLC patients remained controversial. We searched electronic databases for eligible literatures. The primary outcomes were objective response rate (ORR), 6-month and 1-year progression-free survival (PFS) rate. The pooled odds ratio (OR) was calculated using random-effect model. Subgroup analyses stratified by literature type, mutation analysis method, therapeutic regimen, patient origin, and EGFR mutation status in KRAS wild-type patients were proposed. Heterogeneity and publication bias were quantitatively evaluated. A total of ten studies involving 1,677 advanced NSCLC patients with known KRAS mutation status who had received first-line chemotherapy were included. KRAS mutants had lower ORR than wild-type patients (25.1 vs. 34.4 %) significantly (OR 0.67, 95 % CI 0.50-0.88, P = 0.004). Additionally, patients with KRAS mutation had numerically lower 6-month (51.0 vs. 56.8 %) and 1-year (10.3 vs. 13.3 %) PFS rate than wild-type patients, but there was no significant difference between the two groups (OR 0.75, 95 % CI 0.54-1.04, P = 0.08; OR 0.75, 95 % CI 0.47-1.21, P = 0.25). Results of the subgroup analyses were almost concordant with the overall ones. This comprehensive analysis revealed that advanced NSCLC patients with KRAS mutations had significantly lower ORR and potentially lower 6-month/1-year PFS rate compared with wild-type patients after first-line chemotherapy.