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.
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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