Abstract
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.
Keywords
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Article Info
Publication History
Published online: October 04, 2019
Accepted:
September 9,
2019
Received:
July 7,
2019
Associate Editor: Laurence AlbigesIdentification
Copyright
© 2019 Published by Elsevier B.V. on behalf of European Association of Urology.
