Journal of Cancer Research and Clinical Oncology

, Volume 139, Issue 11, pp 1917–1926 | Cite as

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

  • George Dranitsaris
  • Susanne Schmitz
  • Reuben J. Broom
Original Paper



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.


Sorafenib Pazopanib Axitinib Everolimus Indirect comparison Renal cell carcinoma 


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Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • George Dranitsaris
    • 1
    • 4
  • Susanne Schmitz
    • 2
  • Reuben J. Broom
    • 3
  1. 1.University of IoanninaIoanninaGreece
  2. 2.Trinity CollegeDublinIreland
  3. 3.Auckland City HospitalAucklandNew Zealand
  4. 4.TorontoCanada

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