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Published on: April 29, 2014
First-line Systemic Therapy for Metastatic Renal Cell Carcinoma: A Systematic Review and Network Meta-analysis
Christopher J D Wallis1, Zachary Klaassen2, Bimal Bhindi3
1Division of Urology, Department of Surgery, University of Toronto, Toronto, Ontario, Canada.
Context:
In the last decade, there has been a proliferation of treatment options for metastatic renal cell carcinoma (mRCC). However, direct comparative data are lacking for most of these agents.
Objective:
To indirectly compare the efficacy and safety of systemic therapies used in the first-line treatment of mRCC.
Evidence Acquisition:
Medline, EMBASE, Web of Science, and Scopus databases were searched using the OvidSP platform for studies indexed from database inception to October 23, 2017. Abstracts of conferences of relevant medical societies were included, and the systematic search was supplemented by hand search. For the systematic review, we identified any parallel-group randomized controlled trials assessing first-line systemic therapy. For network meta-analysis, we limited these to a clinically-relevant network based on standard practice patterns. Progression-free survival (PFS) was the primary outcome. Overall survival (OS) and grade 3 and 4 adverse events (AEs) were secondary outcomes.
Evidence Synthesis:
In total, 37 trials reporting on 13 128 patients were included in the systematic review. The network meta-analysis comprised 10 trials reporting on 4819 patients. For PFS (10 trials, 4819 patients), there was a high likelihood (SUCRA 91%) that cabozantinib was the preferred treatment. For OS (5 trials, 3379 patients), there was a 48% chance that nivolumab plus ipilimumab was the preferred option. There was a 67% likelihood that nivolumab plus ipilimumab was the best tolerated regime with respect to AEs.
Conclusions:
Cabozantinib and nivolumab plus ipilimumab are likely to be the preferred first-line agents for treating mRCC; however, direct comparative studies are warranted. These findings may provide guidance to patients and clinicians when making treatment decisions and may help inform future direct comparative trials.
Patient Summary:
There are many treatment options for patients diagnosed with metastatic renal cell carcinoma. We indirectly compared the available options and found that cabozantinib and nivolumab plus ipilimumab are likely to be preferable choices as the first-line treatment in this situation.
Insights
Cabozantinib and nivolumab plus ipilimumab show promise as preferred first-line treatments for metastatic renal cell carcinoma (mRCC). Further direct comparative studies are needed to confirm these findings for mRCC patients.
Area of Science:
- Oncology
- Pharmacology
Background:
- Recent advancements have introduced numerous treatment options for metastatic renal cell carcinoma (mRCC).
- Limited direct comparative data exists for many of these systemic therapies.
- This necessitates indirect comparative analyses to guide clinical decision-making.
Purpose of the Study:
- To indirectly compare the efficacy and safety of first-line systemic therapies for metastatic renal cell carcinoma (mRCC).
- To identify potentially preferred treatment options based on available evidence.
Main Methods:
- A systematic search of Medline, EMBASE, Web of Science, and Scopus databases was conducted up to October 2017.
- Included parallel-group randomized controlled trials (RCTs) for first-line systemic therapy in mRCC.
- Network meta-analysis focused on a clinically relevant network, with progression-free survival (PFS) as the primary outcome, and overall survival (OS) and adverse events (AEs) as secondary outcomes.
Main Results:
- The systematic review included 37 trials (13,128 patients); network meta-analysis included 10 trials (4,819 patients).
- Cabozantinib demonstrated a high likelihood (91% SUCRA) of being the preferred treatment for progression-free survival (PFS).
- Nivolumab plus ipilimumab showed a high likelihood (67%) of being the best-tolerated regimen and a 48% chance of being preferred for overall survival (OS).
Conclusions:
- Cabozantinib and nivolumab plus ipilimumab are likely preferred first-line agents for metastatic renal cell carcinoma (mRCC).
- Direct comparative studies are essential to validate these indirect findings.
- These results can assist clinicians and patients in treatment selection and inform future research.
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