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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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.
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).
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.
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.
KeywordsSorafenib Pazopanib Axitinib Everolimus Indirect comparison Renal cell carcinoma
- Calvo E, Escudier B, Motzer RJ et al (2012) Everolimus in metastatic renal cell carcinoma: subgroup analysis of patients with 1 or 2 previous vascular endothelial growth factor receptor-tyrosine kinase inhibitor therapies enrolled in the phase III RECORD-1 study. Eur J Cancer 48:333–339PubMedCrossRefGoogle Scholar
- National Cancer Institute of Canada (2012) Canadian Cancer Statistics 2012. Toronto, Canada (http://www.cancer.ca). Accessed 23 May 2013
- Surveillance Epidemiology and End Results (SEER) (2013) National Cancer Institute 2012. Washington, USA (http://seer.cancer.gov/statfacts/html/lungb.html). Accessed 23 May 2013
- Therasse P, Arbuck SG, Eisenhauer EA et al (2000) New guidelines to evaluate the response to treatment in solid tumours: European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst 92:205–216PubMedCrossRefGoogle Scholar