目的：系统评价纳武单抗联合伊匹单抗对比纳武单抗单用方案治疗恶性肿瘤的有效性和安全性，为临床用药提供循证医学证据。方法：计算机检索PubMed、CNKI、维普、万方等数据库，收集国内外公开发表的纳武单抗联合伊匹单抗对比单用纳武方案单抗治疗恶性肿瘤的临床试验，检索时间均为2000年1月至2022年1月。由两名研究者独立评价纳入研究的质量并提取资料；交叉核对，采用RevMan5.4软件进行Meta分析。结果：共纳入7项研究，含10篇文献。与纳武单抗单用相比，联合治疗组患者的OS显著提高（HR=0.86，95% CI：0.75~0.99，P=0.03），PFS显著延长（HR=0.69，95% CI：0.55~0.85，P=0.000 6）；而治疗相关不良反应事件（OR=3.18，95%CI：1.55~6.55，P=0.002）和停药的不良反应事件（OR=7.11，95% CI：4.85~10.42，P<0.000 01）的发生显著升高。结论：与纳武单抗单用方案相比，纳武单抗联合伊匹单抗方案治疗，可显著延长肿瘤患者的OS及PFS但治疗相关的不良反应事件、停药的不良反应事件的发生较多，故要注意随访定期监测，以预防严重不良反应的发生。

Objective: To systematically evaluate the efficacy and safety of nivolumab plus ipilimumab versus nivolumab monotherapy in the treatment of malignant tumors, so as to provide evidence-based medical proof for clinical administration. Methods: Databases, such as PubMed, CNKI, VIP, and Wanfang Data, were searched from January 2000 to January 2022 to collect the clinical trial data in terms of nivolumab plus ipilimumab versus nivolumab monotherapy for malignant tumors were published in both domestic and abroad. Two reviewers independently evaluated the quality of included RCTs, and extracted and cross-checked the data. RevMan 5. 4 was used for the Meta-analysis. Results: A total of 7 RCTs studies including 10 articles were included. Compared with the nivolumab monotherapy group, the OS of patients in the combined treatment group was significantly improved (HR=0.86, 95% CI: 0. 75-0.99, P=0. 03), and the PFS was significantly prolonged (HR=0.69, 95% CI: 0.55-0.85, P=0.000 6). However, as for safety, treatment-related adverse events (OR=3.18, 95% CI: 1.55-6.55, P=0.002) and adverse events leading to drug discontinuation (OR=7.11, 95% CI: 4.85-10.42, P<0.000 01) in the combination therapy group were significantly higher than those in the monotherapy group. Conclusion: Compared with nivolumab monotherapy, nivolumab plus ipilimumab can significantly improve the OS and PFS of tumor patients, but is also associated with more treatment-related adverse events and adverse events leading to drug discontinuation. Therefore, it is necessary to pay attention to follow-up and regular monitoring to prevent the occurrence of serious adverse reactions.

R730.51；R195.1

福建医科大学启航基金资助项目（No.2020QH1259）；福建省卫生健康青年科研课题资助（No.2019-1-81）