The treatment of metastatic renal cell carcinoma (mRCC) is rapidly changing. During first-line treatment with targeted therapy, patients ultimately develop resistance to therapy and the disease progresses. Recently, cabozantinib has demonstrated a better response rate, progression-free survival and overall survival compared with everolimus after failure of prior targeted therapy in patients with advanced or metastatic renal cell carcinoma (RCC). Cabozantinib is a small-molecule tyrosine kinase inhibitor (TKI). It exerts inhibition of MET, vascular endothelial growth factor receptor type 2, AXL, and many other receptor tyrosine kinases that are also implicated in tumor pathobiology, including RET, KIT, and FLT3. MET drives tumor survival, invasion, angiogenesis, and metastasis through several downstream signaling pathways. AXL has recently been described as an essential mediator of cancer metastasis that mediates crosstalk and resistance to TKIs. MET and AXL are thought to be anti-vascular endothelial growth factor receptor (VEGF) resistance pathways and thus cabozantinib represents a logical choice after progression on initial VEGF therapy. Subgroup analyses examining those with good performance status or visceral and bone metastases indicate that the hazard ratios may be better when using cabozantinib versus everolimus. However, there were no clear statistically significant differences between any subgroups.
Therapeutic advances in urology. 2016 Jan 16 [Epub]
Jose Manuel Ruiz-Morales, Daniel Y C Heng
Tom Baker Cancer Center, Alberta Health Services Cancer Care, University of Calgary, Calgary, Alberta, Canada., Tom Baker Cancer Center, Alberta Health Services Cancer Care, University of Calgary, 1331 29th St NW, Calgary, Alberta, Canada T2N 4N2.