Ciccarese C, et al. – For the treatment of non–clear cell renal cell carcinoma (nccRCC) patients, vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR–TKis) compared with mammalian target of rapamycin (mTOR) inhibitors (mTORi), regarding their efficacy. As compared with mTORi, treatment with TKis significantly improved progression–free survival (PFS), but not overall survival (OS). An investigation highlighted the efficacy of sunitinib as first–line therapy in reducing the risk of progression compared with everolimus. These outcomes supported the standard treatment paradigm broadly used for ccRCC patients.

Methods

• Experts identified prospective studies by searching the MEDLINE/PubMed, Cochrane Library and American Society of Clinical Oncology Meeting abstracts.
• Based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement, data extraction was conduced.
• Progression-free survival (PFS), overall survival (OS) and the overall response rate (ORR) were the measured outcomes.

Results

• With a total of 332 patients evaluable for PFS, four randomised controlled trials were selected for final analysis.
• As compared with mTORi, treatment with TKi significantly reduced the risk of progression (hazard ratio [HR] = 0.71; 95% confidence interval [CI] 0.60–0.84; p < 0.0001).
• When sunitinib was compared with everolimus in first-line setting, this difference remained significant (HR = 0.67; 95% CI, 0.56–0.80; p < 0.00001).
• There was no significant difference between TKi and mTORi (HR = 0.86; 95% CI, 0.67–1.12; p = 0.27), in the 332 patients evaluable for OS.
• Even if treatment with sunitinib doubled the probability of achieving a tumour response, in the 176 evaluable patients, TKis therapy did not improve the ORR when compared with mTORi (relative risk [RR] = 2.21; 95% CI, 0.87–5.60; p = 0.09).