First-Line Treatment of Metastatic Renal Cell Carcinoma in the Immuno-Oncology Era: Systematic Review and Network Meta-analysis - Beyond the Abstract

In recent years there has been an important advance in the systemic treatment of metastatic clear cell renal cell carcinoma. After more than a decade of treatments with targeted therapy (TKI and m-TOR inhibitors, and anti-VEGF antibody) we are now experiencing the era of immune-oncology therapies with IO plus IO, IO plus TKI inhibitor, or IO plus anti-VEGF antibody combinations (IO combinations). Compared to targeted therapy, these IO combinations have been shown to be more efficient and some of them have also shown unprecedented improvement in overall survival (OS) in the first-line treatment setting. Despite this, the lack of head-to-head trials comparing these IO combinations is a gap on what would be the best treatment combination for first-line setting.

In this context, after a thorough literature search including Pubmed/MEDLINE®, EMBASE, LILACS, ClinicalTrials.gov, and the Cochrane Library, we selected four randomized controlled trials with IO combination therapy and sunitinib treatment as the control arm, totalizing 3,758 patients with metastatic clear cell renal cell carcinoma. Using a Bayesian MTC model, we performed an indirect comparison between all the IO treatment combinations. Results indicated for both favorable-risk (FR) and intermediate/poor-risk (IR/PR) patients there was no significant difference in overall survival (OS) between the IO combinations. For FR patients considering both progression-free survival (PFS) and overall response rate (ORR), IO combination with axitinib was more effective than IO plus IO combination (Ipilimumab plus nivolumab). For IR/PR patients there was no significant difference in terms of PFS, however, considering overall response rate (ORR) IO combination with axitinib was more effective than IO plus IO.

Considering the direct comparison with sunitinib, another interesting point of this meta-analysis was the possibility to identify the better choice of treatment for each subgroup risk patient according to different endpoints (OS, PFS, and ORR). For this analysis, we performed a Surface Under the Cumulative Ranking curve (SUCRA) and the results ranged from 0 to 100%. These results are summarized in the tables below.

Direct Comparison Sunitinib
Thus, in the lack of direct comparisons between the IO combinations, all information from our indirect comparison and also from the SUCRA analysis from the direct comparison with sunitinib can help the readers in the daily practice and the choice of first-line treatment for metastatic clear cell renal cell carcinoma.

Written by: Fernando Sabino Marques Monteiro, MD, Latin American Oncology Group (LACOG) – Genito-Urinary Tumors Section, Department of Oncology, Hospital Santa Lucia, Brazil, Twitter: @fsabino_onco

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