A phase I study of cabozantinib (XL184) in patients with renal cell cancer

A decade of pharmacogenomics research on tyrosine kinase inhibitors in metastatic renal cell cancer: a systematic review

“…Many of these second-generation TKIs were assessed for the treatment of mRCC, such as tivozanib, cediranib, and cabozantinib [2][3][4][5]7,8]. Axitinib predominantly blocks the VEGF receptors, with a 50-450 times higher potency than the first-generation TKIs and less off-target activity, which could explain the larger therapeutic window and fewer side effects [2,7].…”

Cabozantinib inhibits tumor growth and metastasis of a patient-derived xenograft model of papillary renal cell carcinoma with MET mutation

“…In a phase I study, Choueiri et al reported that partial response was observed in 7 of 25 (28%) enrolled patients with metastatic ccRCC. 32 Median progression-free survival (PFS) was 12.9 months, and median overall survival was 15.0 months. 32 In a much larger Phase III study of 658 patients with advanced ccRCC, the same investigators observed an objective response rate (ORR) of 21% and median PFS of 7.4 months for cabozantinib, compared to ORR of 5% and PFS of 3.8 months for everolimus, a standard secondline treatment for advanced ccRCC.…”

“…32 Median progression-free survival (PFS) was 12.9 months, and median overall survival was 15.0 months. 32 In a much larger Phase III study of 658 patients with advanced ccRCC, the same investigators observed an objective response rate (ORR) of 21% and median PFS of 7.4 months for cabozantinib, compared to ORR of 5% and PFS of 3.8 months for everolimus, a standard secondline treatment for advanced ccRCC. 33 The high efficacy of cabozantinib in advanced ccRCC is not surprising since it inhibits multiple tyrosine kinases including MET, VEGF receptors and AXL, and MET and AXL are upregulated as a consequence of VHL inactivation commonly observed in ccRCC.…”

Moving beyond vascular endothelial growth factor-targeted therapy in renal cell cancer: latest evidence and therapeutic implications

“…53 An initial phase I study demonstrated promising antitumor activity and safety with cabozantinib in patients with mRCC resistant to VEGF-R and mTOR inhibitors. 54 This paved the way for a landmark phase III study METEOR, in which 658 mRCC patients who had received at least one VEGF-R-targeting TKI were randomized to receive either second-line cabozantinib or everolimus. 55 56 These promising results provided proof of principle that co-inhibition of the MET/ AXL pathways is effective and clinically meaningful, and cabozantinib has now received regulatory approval for the treatment of mRCC after progression on VEGF-R TKI therapy in the USA.…”