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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

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Abstract

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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All data generated or analyzed during this study are included in this article and its Supplementary Information files.

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Funding

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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Author notes

  1. Leitao Sun, Leyin Zhang, and Jieru Yu contributed equally to this work.

Authors and Affiliations

  1. The First Clinical Medical College of Zhejiang, Chinese Medical University, Hangzhou, 310053, Zhejiang, China

    Leitao Sun, Leyin Zhang & Chao Shi

  2. College of Basic Medical Science, Zhejiang Chinese Medical University, Hangzhou, 310053, Zhejiang, China

    Jieru Yu

  3. The Second Clinical Medical College of Zhejiang, Chinese Medical University, Hangzhou, 310053, Zhejiang, China

    Yiwen Zhou

  4. Department of Cancer Medicine, Hammersmith Hospital, Imperial College Healthcare NHS Trust, London, W12 0HS, UK

    Harpreet S. Wasan

  5. Department of Medical Oncology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, 310006, Zhejiang, China

    Leitao Sun & Shanming Ruan

  6. Department of Traditional Chinese Medicine, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, 310006, Zhejiang, China

    Dawei Huang

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Contributions

SR, HSW, and DH contributed to the design and conception of the study. YZ and JY carried out the collection and assembly of data. LZ and CS performed the data analysis and interpretation. LS and LZ wrote the manuscript, SR revised the manuscript, then SR and DH gave the final approval of manuscript.

Corresponding authors

Correspondence to Shanming Ruan or Dawei Huang.

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We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work, there is no professional or other personal interest of any nature or kind in any product, service and company that could be construed as influencing the position presented in, or the review of, the manuscript entitled.

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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

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