Introduction: This meta-analysis aimed to assess the effectiveness and safety of combining anlotinib with chemotherapy in treating patients with small cell lung cancer (SCLC). Methods: We systematically searched a range of databases, including PubMed, Embase, Cochrane Library, and Web of Science, up to July 28, 2023, complemented by searches in Chinese databases such as CNKI, Wanfang, and VIP, through July 4, 2023. The outcomes analyzed were objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), median PFS (mPFS), overall survival (OS), vascular endothelial growth factor (VEGF) levels, and the adverse events. Results: The analysis, which integrated data from 16 studies encompassing 1,083 patients, demonstrated that the combined treatment of anlotinib and chemotherapy significantly outperformed either anlotinib or chemotherapy alone in enhancing the ORR, DCR, and mPFS. Furthermore, this combination therapy also resulted in improved PFS, 1-year and 2-year overall OS, and reduced levels of VEGF) compared to chemotherapy alone, with all comparisons reaching statistical significance (p < 0.05). The combination of anlotinib with chemotherapy exhibited a considerably elevated risk of developing leukopenia (RR: 1.41, 95% CI: 1.09–1.82, p = 0.008). The subgroup analyses indicated the anlotinib plus etoposide group and anlotinib plus irinotecan were superior to the etoposide and the irinotecan groups, respectively, in terms of ORR outcome and DCR outcome. The subgroup analysis revealed that the combination of anlotinib and etoposide significantly increased the risk of thrombocytopenia and myelosuppression compared to etoposide alone. In patients with a history of one or an unspecified number of chemotherapy cycles, the integration of anlotinib into the chemotherapy regimen improved DCR. Conversely, in those who had undergone more than two prior treatment cycles, the risk of myelosuppression was heightened with the addition of anlotinib. Lastly, the risk of gastrointestinal adverse events was increased in patients receiving more than two treatment cycles of anlotinib plus chemotherapy compared to anlotinib monotherapy. Conclusion: The findings of this investigation imply that the integration of anlotinib into chemotherapy regimens may enhance PFS, ORR, DCR, and OS in SCLC patients. This meta-analysis presents novel therapeutic prospects for SCLC, suggesting that the synergistic approach of anlotinib and chemotherapy could markedly enhance treatment outcomes for this patient population.

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