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. 2021 Oct 29:13:17562872211053189.
doi: 10.1177/17562872211053189. eCollection 2021 Jan-Dec.

Is there a preferred first-line therapy for metastatic renal cell carcinoma? A network meta-analysis

Carlo Cattrini  1 , Carlo Messina  2 , Chiara Airoldi  3 , Sebastiano Buti  4 , Giandomenico Roviello  5 , Alessia Mennitto  1 , Orazio Caffo  6 , Alessandra Gennari  1 , Melissa Bersanelli  7
Affiliations

Is there a preferred first-line therapy for metastatic renal cell carcinoma? A network meta-analysis

Carlo Cattrini et al. Ther Adv Urol. .

Abstract

Background: In recent years, new therapeutic combinations based on immunotherapy provided significant benefits as a first-line treatment for patients with advanced renal cell carcinoma (mRCC).

Objective: This work aims to address the lack of head-to-head comparisons and the uncertainty of the benefit from immunotherapy-based combinations in all the International Metastatic RCC Database Consortium (IMDC) subgroups.

Design setting and participants: A systematic review and a network meta-analysis were performed. Overall survival (OS) in the intention-to-treat (ITT) population was the primary endpoint. OS according to IMDC subgroups (favorable, intermediate, poor), PD-L1 expression, and grade ⩾3 adverse events (AEs) were secondary endpoints. A SUCRA analysis was performed.

Results and limitations: Six randomized phase III trials with 5121 patients were included. There was a high likelihood (82%) that nivolumab-cabozantinib was the preferred treatment in OS. The benefit of ICI-based combinations over sunitinib was unclear in the favorable-risk subgroup. Nivolumab-ipilimumab had the best risk/benefit ratio among all the ICI-based combinations. The limitations were the lack of individual patient data; the heterogeneity of patients' characteristics, trial designs, and follow-up times; and a limited number of studies for indirect comparisons.

Conclusions: A customized approach for the first-line treatment of patients with mRCC should consider the risk/benefit profile of each treatment option, especially considering the likeliness of long-term survival finally reached in this setting.

Keywords: first-line; immune checkpoint inhibitors; meta-analysis; renal cell carcinoma; tyrosine kinase inhibitors.

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Conflict of interest statement

Conflict of interest statement: The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: C.C. received Travel/Accommodation/Expenses from Novartis, Pfizer, Janssen, and Ipsen; advisory board from Janssen. C.M. received honoraria as a speaker for scientific events from Astellas and Ipsen. S.B. received honoraria as a speaker at scientific events and advisory role from Bristol-Myers Squibb (BMS), Pfizer, MSD, Ipsen, Roche, Eli-Lilly, AstraZeneca, and Novartis; he also received research funding from Novartis. O.C. received honoraria as advisor/speaker from Astellas, AstraZeneca, Bayer, Janssen, MSD, Pfizer, and Sanofi. A.G. has declared consulting/advisory role for Roche, MSD, Eli Lilly, Pierre Fabre, EISAI, and Daichii Sankyo; Speakers Bureau from Eisai, Novartis, Eli Lilly, Roche, Teva, Gentili, Pfizer, Astra Zeneca, Celgene, and Daichii Sankyo; and research funds from EISAI, Eli Lilly, and Roche. M.B. received research funding from Roche S.p.A., Seqirus UK, Pfizer, Novartis, BMS, Astra Zeneca, and Sanofi Genzyme; honoraria as a speaker at scientific events from Bristol-Myers Squibb (BMS), Novartis, Astra Zeneca, Pierre Fabre, and Pfizer; fees as a consultant for advisory role from Novartis, BMS, IPSEN, and Pfizer; and fees for copyright transfer and consultancies from Sciclone Pharmaceuticals. All the other authors declare no conflicts of interest.

Figures

Figure 1.
Figure 1.
PRISMA flow chart of the studies’ selection process.
Figure 2.
Figure 2.
Forest plot of overall survival (OS) (a) and grade ⩾3 toxicity (b) in the intention-to-treat (ITT) population. Analysis of OS in the International Metastatic RCC Database Consortium (IMDC) favorable (c), intermediate-poor (d), intermediate (e), and poor (f) subgroups. Clustered analysis of efficacy and AEs (g) according to SUCRA values. Heterogeneity was negligible, with I2 lower than 20% for all networks performed, and a fixed effect model was applied.
Figure 3.
Figure 3.
Forest plot of overall survival (OS) in the PD-L1-positive (a) and PD-L1-negative (b) subgroup (1% threshold).
See this image and copyright information in PMC

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