Systematic review and meta-analysis of target terapies for the treatment of metastatic renal cancer

Abstract

Objectives: At present there are several drugs for the treatment of advanced renal cell carcinoma (ARCC). The main objective of this work was to perform a systematic review (SR) and meta-analysis (MA) of clinical randomized studies that compared target cell therapies (TCT). Materials and Methods: SR identified clinical randomized trials that compared TCT versus interferon-alpha in the treatment of patients with ARCC. In order to analyze efficiency, it was evaluated free-survival progression (FSP), total survival (TS) and response rate (RR). Results: In relation to first line treatment, seven studies of TCT were identified using sunitinib, sorafenib, bevacizumab and temsirolimus; and two studies with sorafenib and everolimus for second line treatment. Relative risk (RRi) of MA for FSP of first line therapies was: 0.83, CI = 0.78-0.87, I2 = 94% and p < 0.00001. Best results of RR of specific FSP among studies were: 0.38, sunitinib, CI = 0.25-0.58, bevacizumab, 0.62, CI = 0.47-0.83; and temsirolimus, 0.78, CI = 0.70-0.87. MA didn't show any benefit regarding TS of first line treatment of all analyzed drugs. As for RR significant results were: sunitinib, 3.83 CI = 2.86-5.12; bevacizumab, 2.52 CI = 1.78-3.57 and bevacizumab, 1.97 CI = 1.43-2.71. Conclusions: For first line treatment, sunitinib was the most effective TCT in relation to FPS; there was no alteration of TS and RR was small but significant for sunitinib and bevacizumab. Available studies could not conclude any results for second line treatments. Systematic review and meta-analysis of target terapies

Sunitinib therapy for metastatic renal cell carcinoma: A urologist’s perspective

“…However, a recent systematic review and meta-analysis of targeted therapies for the treatment of mRCC suggested that for first-line treatment, sunitinib was the most effective in relation to PFS, OS, and response rate. 11 In our study of 28 patients with mRCC, objective response rate (CR+PR) was 48% and clinical benefit rates (CR+PR+SD) of 81%. These results are encouraging and compare with data from Motzer's trial, 7 indicating the reproducibility of the trial results in clinical practice.…”

“…However, a recent systematic review and meta-analysis of targeted therapies for the treatment of mRCC suggested that for first-line treatment, sunitinib was the most effective in relation to PFS, OS, and response rate. 11…”

Sunitinib Enables a Clinical and Pathological Complete Remission of Metastatic Renal Cell Carcinoma (mRCC)

“…Sunitinib has been shown to markedly prolong progression-free survival (PFS) and overall survival (OS) in patients with mRCC 2 . Although it has been reported that some patients achieve a complete remission (CR) with sunitinib therapy, clinical and pathological remission has seldom been described.…”

Induction of Epithelial-Mesenchymal Transition via Activation of Epidermal Growth Factor Receptor Contributes to Sunitinib Resistance in Human Renal Cell Carcinoma Cell Lines

“…Sunitinib is a smallmolecule multiple-receptor tyrosine kinase (RTK) inhibitor targeting vascular endothelial growth factor receptors (VEGFRs: VEGFR-1, VEGFR-2, and VEGFR-3), platelet-derived growth factor receptors (PDGFRs: PDGFR-a and PDGFR-b), FMS-like tyrosine kinase 3, and the stem cell growth factor receptor KIT, and rearranged during transfection (Faivre et al, 2007;Roskoski, 2007). A meta-analysis comparing the clinical efficacy among targeted agents for the treatment of metastatic RCC has shown that sunitinib is more effective than other agents (Durán et al, 2013;Leung et al, 2014). Although most patients benefit from tyrosine kinase inhibitor treatment, including sunitinib, some still exhibit early progression.…”