Anlotinib is presently used as a third‑line treatment for non‑small cell lung cancer. However, it is not yet reported whether combining anlotinib with S‑1 as a third‑ or later‑line treatment offers superior outcomes compared with anlotinib alone. The present meta‑analysis aimed to address this question by systematically searching the PubMed, Embase, Web of Science, Cochrane Library, CMB and China National Knowledge Infrastructure databases for eligible studies published from the establishment of the database to January 10, 2024. Primary outcomes of interest included progression‑free survival (PFS), overall survival (OS), objective response rate (ORR), disease control rate (DCR) and the incidence of adverse effects, which were presented as hazard ratios and 95% CIs. The present analysis included 5 retrospective studies with a total of 317 patients and compared the outcomes of patients treated with a combination of anlotinib and S‑1 (experimental group) compared with anlotinib alone (control group). The combination treatment significantly improved PFS, OS, ORR and DCR in the experimental group compared with the control group. Bone marrow suppression and fatigue were significantly higher in the experimental group compared with the control group. However, incidences of hypertension, proteinuria, gastrointestinal adverse reactions, hepatic and renal insufficiency and functional hand‑foot syndrome were higher in the control group compared with the experimental group, but there was no statistical significance. In summary, combining anlotinib with S‑1 may be more effective compared with anlotinib alone for treating advanced non‑small cell lung cancer. Despite the higher incidence of adverse reactions with the combination therapy, these reactions could be considered manageable and controllable.

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