title: The efficacy of first-line chemotherapy is associated with KRAS mutation status in patients with advanced non-small cell lung cancer: a meta-analysis.
abstract: 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.
authors: State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China.
authors: Yaxiong
authors: Y
authors: Zhang
authors: Wenfeng
authors: W
authors: Fang
authors: Yue
authors: Y
authors: Yan
authors: Mengyao
authors: M
authors: Wang
authors: Shiyang
authors: S
authors: Kang
authors: Jin
authors: J
authors: Sheng
authors: Jianhua
authors: J
authors: Zhan
authors: Nan
authors: N
authors: Chen
authors: Shaodong
authors: S
authors: Hong
authors: Yunpeng
authors: Y
authors: Yang
authors: Yuxiang
authors: Y
authors: Ma
authors: Dacheng
authors: D
authors: He
authors: Tao
authors: T
authors: Qin
authors: Ting
authors: T
authors: Zhou
authors: Yanna
authors: Y
authors: Tang
authors: Xiaobo
authors: X
authors: He
authors: Wenhua
authors: W
authors: Liang
authors: Li
authors: L
authors: Zhang
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D018572:Disease-Free Survival; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D009154:Mutation; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics*; D017594:Publication Bias; D016896:Treatment Outcome
chemical_list: C117307:KRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)