Although it’s widely known that targeted therapy against angiogenesis and immunotherapy agents showed survival benefit over chemoradiotherapy in advanced or metastatic renal cell carcinoma, some patients still cannot receive a satisfied prognosis. We performed a systematic review and meta-analysis to explore the efficacy and safety of anti-angiogenic agents combined with immune checkpoint inhibitors. We conducted a search for randomized controlled trials in Pubmed, Embase, Cochrane, and major conference. Enrolled eligible studies and extracted data were completed by two investigators to compare OS, PFS, and ORR both in PD-L1 and ITT subset. Then, we calculated the pooled RR and 95% CI of all-grade and high-grade adverse effects to study its safety. Besides, we assessed the heterogeneity through subgroup and sensitivity analysis. A total of three RCTs covering 2662 patients were enrolled. In PFS analysis, the estimated HR for ITT subset was 0.74 with 95% CI of 0.65 to 0.84 and for PD-L1 subset was 0.65 with 95% CI of 0.56 to 0.76. And in OS analysis, the result was 0.74 with 95% CI of 0.53 to 1.03 in ITT subset and 0.74 with 95% CI of 0.56 to 0.96 in PD-L1 subset. As for ORR analysis, combination therapy showed advantage rather than monotherapy in ITT subset (RR 1.54; 95% CI 1.11 to 2.14), but conversely in PD-L1 positive subset (RR 1.64; 95% CI 0.94 to 2.84). Additionally, combination therapy failed to show obvious safety in most immune-related adverse events, whatever in all-grade or high grade.
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This study was financially supported by National Natural Science Foundation of China (Minhe Shen, No. 81573902); Natural Science Foundation of Zhejiang Province (Shanming Ruan, No. LY17H270007); China Postdoctoral Science Foundation (Shanming Ruan, No. 2017M612040/2018T110610); Zhejiang Provincial Program for the Cultivation of High-Level Innovative Health Talents (Shanming Ruan, No. 2015-43); Program for the Cultivation of Youth talents in China Association of Chinese Medicine (Shanming Ruan, No. QNRC2-C08); Zhejiang Provincial Program for the Cultivation of the Young and Middle-Aged Academic Leaders in Colleges and Universities (Shanming Ruan, No. 2017-248); Zhejiang Provincial Project for the key discipline of Traditional Chinese Medicine (Yong Guo, No. 2017-XK-A09).
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Dawei Huang and Shanming Ruan are co-corresponding author in this work.
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Sun, L., Zhang, L., Yu, J. et al. To be or not to be: whether anti-angiogenic agent combined with immune checkpoint inhibitoris necessary in the treatment of advanced or metastatic renal cell carcinoma. Med Oncol 37, 15 (2020). https://doi.org/10.1007/s12032-020-1340-7
- Combination therapy
- Anti-angiogenic agent
- Immune checkpoint inhibitor
- Renal cell carcinoma