Abstract
BACKGROUND: To systematically evaluate the efficacy and safety of anlotinib plus epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) in the treatment of advanced non-small cell lung cancer (NSCLC) with EGFR mutations. METHODS: This meta-analysis was registered with PROSPERO (Registration number: CRD420251102861). Up to July 11, 2025, the databases of PubMed, EMBASE, Cochrane Library, ClinicalTrials.gov, China National Knowledge Infrastructure, Chinese Biomedical Literature, China Science and Technology Journal, and Wanfang were searched, and the randomized controlled clinical trials of anlotinib plus EGFR-TKI in the treatment of advanced EGFR-mutant NSCLC were included. Two investigators independently screened the literature, assessed the quality of the included literature, and extracted the literature data. Revman5.4 software was used for meta-analysis. RESULTS: A total of 993 patients were included in 10 randomized controlled clinical trials. The results of meta-analysis showed that compared with the control group (EGFR-TKI monotherapy), the experimental group (anlotinib plus EGFR-TKI) significantly improved the objective response rate (relative risk [RR] = 1.38, 95% confidence interval [CI]: 1.26-1.52, P < .00001) and disease control rate (RR = 1.17, 95% CI: 1.07-1.28, P = .0003), prolonged the progression-free survival (hazard ratio = 0.60, 95% CI: 0.46-0.78, P = .0002), but did not increase the 1-year and 2-year overall survival rates (RR = 1.37, 95% CI: 0.81-2.30, P = .24; RR = 1.65, 95% CI: 0.40-6.76, P = .49) of the patients. In terms of adverse events, the incidence of rash, hypertension, proteinuria, hand-foot syndrome, oral mucositis, diarrhea, fatigue, hemoptysis, and leukopenia was higher in the experimental group than in the control group (P < .05). CONCLUSION: Compared with EGFR-TKI monotherapy, anlotinib plus EGFR-TKI provides some clinical benefits for patients with advanced NSCLC harboring EGFR mutations, but it does not significantly improve long-term survival and has higher toxicity.