Abstract
Background
Randomized controlled trials (RCTs) of multikinase inhibitors sunitinib, sorafenib,
and pazopanib have reported efficacy compared with results from placebo and interferon-α
(INF-α). To date, these drugs have not been compared in head-to-head trials.
Objective
To review systematically the evidence of clinical effectiveness of multikinase inhibitors
in the treatment of metastatic renal cell carcinoma (mRCC) and, via an indirect meta-analysis,
to determine an optimal treatment among these agents.
Methods
A systematic literature search of MEDLINE, EMBASE, CANCERLIT, and Cochrane controlled
trials register databases was performed. All RCTs of multikinase inhibitors (sorafenib,
sunitinib, and pazopanib) used to treat mRCC were included. The study selection, data
extraction, and quality assessment were performed independently by 2 reviewers, with
all disagreements being resolved by consensus. The effects of multikinase inhibitors
on progression-free survival (PFS) were compared using an indirect treatment comparison
method with INF-α or placebo as a comparator.
Results
Four studies were included. Two studies examined sunitinib or sorafenib versus IFN-α,
and the other 2 studies investigated sorafenib or pazopanib versus placebo. Compared
with placebo, 2 interventions reported improvement for PFS (sorafenib: hazard ratio
[HR] = 0.44, P = 0.01; pazopanib: HR = 0.46, P = 0.0001), whereas only sunitinib improved PFS over IFN-α (HR = 0.539, P = 0.001). An indirect comparison suggests that sunitinib is likely to demonstrate
greater clinical benefit than sorafenib in terms of PFS (HR = 0.47; 95% CI, 0.316–0.713;
P < 0.001), using IFN-α as the comparator. Sorafenib was not statistically different
from pazopanib using placebo as the comparator in the indirect comparison (HR = 0.957;
95% CI, 0.657–1.39; P = 0.24).
Conclusion
Some multikinase inhibitors have a favorably reported PFS for patients with mRCC compared
with results using IFN-α or placebo. Our findings suggest that sunitinib might offer
some clinical benefit over sorafenib in terms of PFS. No statistical difference was
found between sorafenib and pazopanib treatments. However, these conclusions are based
on 2 indirect comparisons of single RCTs. More RCTs are required to confirm these
findings and investigate the clinical effectiveness of multikinase inhibitors in the
treatment of mRCC.
Key words
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Article info
Publication history
Accepted:
May 3,
2011
Identification
Copyright
© 2011 Published by Elsevier Inc.
