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Updated: Oct 14, 2025
A Syngeneic Mouse Model of Metastatic Renal Cell Carcinoma for Quantitative and Longitudinal Assessment of Preclinical Therapies
Published on: April 12, 2017
Is there a preferred first-line therapy for metastatic renal cell carcinoma? A network meta-analysis
Carlo Cattrini1, Carlo Messina2, Chiara Airoldi3
1Division of Oncology, University Hospital 'Maggiore della Carità', Novara, Italy.
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.
Insights
Nivolumab-cabozantinib shows high likelihood for improved survival in advanced renal cell carcinoma (mRCC). A customized approach is recommended, considering risk/benefit for each patient.
Area of Science:
- Oncology
- Clinical Trials
- Immunotherapy
Background:
- Advanced renal cell carcinoma (mRCC) treatment has seen significant benefits from first-line immunotherapy combinations.
- Uncertainty remains regarding the comparative effectiveness of these combinations across different patient subgroups.
Purpose of the Study:
- To address the lack of head-to-head comparisons for immunotherapy combinations in mRCC.
- To evaluate the benefit of immunotherapy combinations across International Metastatic RCC Database Consortium (IMDC) subgroups.
Main Methods:
- Systematic review and network meta-analysis of six randomized phase III trials (5121 patients).
- Primary endpoint: Overall Survival (OS) in the intention-to-treat (ITT) population.
- Secondary endpoints: OS by IMDC subgroups, PD-L1 expression, and grade ≥3 adverse events (AEs); SUCRA analysis performed.
Main Results:
- Nivolumab-cabozantinib demonstrated an 82% likelihood of being the preferred treatment for OS.
- Benefit of ICI-based combinations over sunitinib was unclear in the favorable-risk subgroup.
- Nivolumab-ipilimumab offered the best risk/benefit ratio among ICI-based combinations.
Conclusions:
- A personalized approach to first-line mRCC treatment is crucial.
- Consideration of the risk/benefit profile of each treatment option is essential for optimizing long-term survival.
- Limitations include lack of individual patient data and heterogeneity across trials.
