Efficacy and safety of immunological checkpoint inhibitors combined with anti-angiogenic drugs in first-line treatment of metastatic renal cell carcinoma: a systematic review and meta-analysis

免疫检查点抑制剂联合抗血管生成药物一线治疗转移性肾细胞癌的疗效和安全性:系统评价和荟萃分析

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Abstract

BACKGROUND: Immune checkpoint inhibitors (ICIs) have shown promising results for the second-line treatment of metastatic renal cell carcinoma (mRCC). Several randomized controlled trials have so far also evaluated the efficacy of ICIs for first-line treatment of mRCC. In this study, we conducted a meta-analysis of relevant studies to further clarify the efficacy and safety of ICIs combined with anti-angiogenic drugs for the treatment of mRCC. METHODS: We searched the PubMed, Embase, and Cochrane libraries for RCT trials of ICIs combined with anti-angiogenic drugs for first-line treatment of mRCC published before November 20, 2019. A meta-analysis was conducted based on methodological recommendations by the Cochrane Collaboration. RESULTS: Four articles with a total of 2,967 patients met the inclusion criteria. Our meta-analysis revealed that progression-free survival (PFS) and objective response rate (ORR) were significantly improved in the experimental group while there was no significant difference in overall survival (OS) (HR 0.75, 95% CI: 0.67-0.84; HR 1.43, 95% CI: 1.07-1.91; HR 0.74, 95% CI: 0.53-1.03). After stratification for PD-L1 expression, OS, PFS, and ORR of PD-L1 positive patients were significantly increased in the experimental group (HR 0.74, 95% CI: 0.56-0.96; HR 1.66, 95% CI: 1.11-2.49; HR 0.65, 95% CI: 0.57-0.75). CONCLUSIONS: Immunological checkpoint inhibitors combined with anti-angiogenic drugs as a first-line treatment for mRCC improve PFS and ORR. This effect is more pronounced in PD-L1 positive patients, where ICIs also improve OS. ICIs do not increase the incidence of adverse events.

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