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J Cancer Res Clin Oncol. 2013 Nov;139(11):1917-26. doi: 10.1007/s00432-013-1510-5. Epub 2013 Sep 14.

Small molecule targeted therapies for the second-line treatment for metastatic renal cell carcinoma: a systematic review and indirect comparison of safety and efficacy.

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1
University of Ioannina, Ioannina, Greece, george.dranitsaris@gmail.com.

Abstract

BACKGROUND:

Patients with metastatic renal cell carcinoma (mRCC) and a good performance status typically receive an anti-vascular endothelial growth factor receptor (VEGFR) TKI (sunitinib or pazopanib) as initial therapy. Upon disease progression or intolerance, there are four orally administered agents approved in the second-line setting (including cytokine-refractory). However, head-to-head comparative trial data are limited. In this study, an indirect statistical comparison of safety and efficacy was undertaken between axitinib, sorafenib, pazopanib and everolimus in second-line therapy mRCC.

METHODS:

A systematic review of major databases was conducted from January 2005 to June 2013 for randomized controlled trials (RCTs) evaluating at least one of the four agents in second-line mRCC. Bayesian mixed treatment comparison models were fitted to assess relative effectiveness on multiple endpoints such as objective response rates, dose-limiting grade III/IV toxicities, treatment discontinuations and progression-free survival (PFS).

RESULTS:

Four RCTs met the inclusion criteria. All four agents seem able to induce tumor shrinkage and to provide patients with a clinically meaningful PFS benefit. Axitinib was superior to pazopanib [hazard ratio (HR) 0.64; 95 % credible interval (95 % Crl) 0.42-0.96] and sorafenib (HR 0.70; 95 % Crl 0.57-0.87) in terms of PFS. However, axitinib was associated with an elevated risk of fatigue and to a lesser extent stomatitis.

CONCLUSIONS:

Keeping in mind the caveats associated with cross-trial statistical comparisons, axitinib provides superior PFS relative to pazopanib and sorafenib. Everolimus, an mammalian target of rapamycin inhibitor, is mechanistically distinct from the other agents and remains a useful option for patient's post-anti-VEGFR TKI failure.

PMID:
24037486
DOI:
10.1007/s00432-013-1510-5
[Indexed for MEDLINE]
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