Preprint Article Version 1 This version is not peer-reviewed

Comparative Efficacy of First-Line Immune-Based Combination Therapies in Metastatic Renal Cell Carcinoma. A Systematic Review and Network Meta-Analysis.

Version 1 : Received: 19 May 2020 / Approved: 22 May 2020 / Online: 22 May 2020 (11:35:36 CEST)

How to cite: ELAIDI, R.; PHAN, L.; Borchiellini, D.; BARTHELEMY, P.; Ravaud, A.; OUDARD, S.; VANO, Y. Comparative Efficacy of First-Line Immune-Based Combination Therapies in Metastatic Renal Cell Carcinoma. A Systematic Review and Network Meta-Analysis.. Preprints 2020, 2020050353 (doi: 10.20944/preprints202005.0353.v1). ELAIDI, R.; PHAN, L.; Borchiellini, D.; BARTHELEMY, P.; Ravaud, A.; OUDARD, S.; VANO, Y. Comparative Efficacy of First-Line Immune-Based Combination Therapies in Metastatic Renal Cell Carcinoma. A Systematic Review and Network Meta-Analysis.. Preprints 2020, 2020050353 (doi: 10.20944/preprints202005.0353.v1).

Abstract

Background: Three drug-combinations, ipilimumab-nivolumab (Ipi-Nivo), pembrolizumab-axitinib (Pembro-Axi) and avelumab-axitinib (Ave-Axi), have received regulatory approvals in USA and Europe for the treatment of metastatic renal cell carcinoma with clear cell component (mRCC). However, no head-to-head comparison data are available to identify the best option. Therefore, we aimed to compare these new treatments in the first-line setting. Methods: We conducted a systematic search in Pubmed, the Cochrane library and clinicaltri-al.gov website from January 2015 to October 2019, for any randomized controlled trials of treatment-naïve patients with mRCC. The process was performed according to PRISMA guide-lines. We performed a Bayesian network meta-analysis with two different approaches. The out-comes for analysis were overall survival, progression-free survival, and objective response rate. Results: Our search identified 3 published phase 3 randomized clinical trials (2835 patients). In the contrast-based model, Ave-Axi (SUCRA: 83%) and Pembro-Axi (SUCRA: 80%) exhibited the best ranking probabilities for PFS. For OS, Pembro-Axi (SUCRA: 96%) was the most pref-erable option against Ave-Axi and Ipi-Nivo. Objective response rate analysis showed Ave-Axi as the best (SUCRA= 94%) and Pembro-Axi as second best option. In the parametric models, risk of progression was comparable for Ave-Axi and Ipi-Nivo, whereas Pembro-Axi exhibited a lower risk during the first 6 months of treatment and a higher risk afterward. Furthermore, Pembro-Axi exhibited a net advantage in terms of OS over the two other regimens, while Ave-Axi was the least preferable option. Conclusions: Overall evidences suggested pembrolizumab plus axitinib may be the best option.

Subject Areas

metastatic renal cell carcinoma; immune-based combination therapies; network meta-analysis

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