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Updated: Jan 6, 2026
A Syngeneic Mouse Model of Metastatic Renal Cell Carcinoma for Quantitative and Longitudinal Assessment of Preclinical Therapies
Published on: April 12, 2017
First-line Treatment of Metastatic Renal Cell Carcinoma: A Systematic Review and Network Meta-analysis
Andrew W Hahn1, Zachary Klaassen2, Neeraj Agarwal1
1Division of Oncology, Department of Internal Medicine, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA.
Context:
No head-to-head clinical trials compare contemporary first-line therapies for metastatic renal cell carcinoma (mRCC). A network meta-analysis provides an approach for quantitative analysis.
Objective:
To indirectly compare the efficacy and safety of first-line treatments for mRCC in the intention-to-treat (ITT) population and by clinical risk group.
Evidence Acquisition:
An updated systematic review from database inception to February 17, 2019 identified all parallel-group randomized controlled trials assessing first-line therapy for mRCC. "Clinically relevant" studies were selected for a network meta-analysis. Progression-free survival (PFS) was the primary outcome. Overall survival (OS), overall response rate (ORR), and grade 3 and 4 adverse events (AEs) were secondary outcomes.
Evidence Synthesis:
We identified 12 relevant trials: 12 reported outcomes for PFS, nine for OS, 10 for ORR, and nine for AEs. In the ITT population, cabozantinib (surface under the cumulative ranking curves [SUCRA] 84%), avelumab plus axitinib (SUCRA 68%), and pembrolizumab plus axitinib (SUCRA 82%) were superior to the other agents for PFS; pembrolizumab plus axitinib appeared superior for OS (SUCRA 95%); and atezolizumab demonstrated the lowest likelihood of AEs (SUCRA 100%). Findings were similar in the intermediate/poor-risk subgroup. Based on the limited data available, avelumab plus axitinib may be preferred in patients with favorable-risk disease.
Conclusions:
The optimal first-line treatment for mRCC appears to differ by efficacy endpoint, toxicity, and clinical risk group. Direct comparative studies remain important in guiding treatment choice.
Patient Summary:
Head-to-head comparisons do not exist for the newest treatments of metastatic renal cell carcinoma (mRCC). In an indirect comparison, we found that pembrolizumab plus axitinib and cabozantinib are good options for most patients with mRCC.
Insights
This network meta-analysis compared first-line treatments for metastatic renal cell carcinoma (mRCC). Pembrolizumab plus axitinib and cabozantinib show promise for most patients, but optimal choice varies by risk group and endpoint.
Area of Science:
- Oncology
- Clinical Trials
- Pharmacoeconomics
Background:
- No direct head-to-head trials exist for contemporary first-line therapies in metastatic renal cell carcinoma (mRCC).
- Network meta-analysis offers a quantitative approach to indirectly compare treatment efficacy and safety.
Purpose of the Study:
- To indirectly compare the efficacy and safety of first-line treatments for mRCC.
- To analyze outcomes in the overall intention-to-treat (ITT) population and by clinical risk groups.
Main Methods:
- An updated systematic review identified parallel-group randomized controlled trials for first-line mRCC therapy.
- Network meta-analysis was performed on clinically relevant studies.
- Progression-free survival (PFS) was the primary outcome; overall survival (OS), overall response rate (ORR), and adverse events (AEs) were secondary.
Main Results:
- Cabozantinib, avelumab plus axitinib, and pembrolizumab plus axitinib showed superiority for PFS in the ITT population.
- Pembrolizumab plus axitinib demonstrated superior OS, while atezolizumab had the lowest likelihood of AEs.
- Findings were consistent in intermediate/poor-risk subgroups; avelumab plus axitinib may be preferred for favorable-risk disease.
Conclusions:
- Optimal first-line mRCC treatment choice depends on efficacy endpoints, toxicity profiles, and patient risk stratification.
- Direct comparative studies are crucial for definitive treatment guidance.
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