TY - JOUR
T1 - Cabozantinib
T2 - an Active Novel Multikinase Inhibitor in Renal Cell Carcinoma
AU - Tannir, Nizar M.
AU - Schwab, Gisela
AU - Grünwald, Viktor
N1 - Funding Information:
Medical writing and editorial support were provided by David W. Markby (Exelixis) and Fishawack Communications and were funded by Exelixis, Inc.
Publisher Copyright:
© 2017, The Author(s).
PY - 2017/2/1
Y1 - 2017/2/1
N2 - Clear cell renal cell carcinoma (RCC) is characterized by inactivation of the von Hippel-Lindau (VHL) tumor suppressor gene. VHL loss drives tumor angiogenesis and accounts for the clinical activity of VEGF receptor (VEGFR) tyrosine kinase inhibitors (TKIs), the first-line standard of care for advanced RCC. Within the last year, three new second-line treatments have received FDA approval for use after anti-angiogenic therapy: the immune checkpoint inhibitor nivolumab, the TKI cabozantinib, and the combination of the TKI lenvatinib and the mTOR inhibitor everolimus. Cabozantinib inhibits VEGFRs, MET, and AXL, kinases that promote tumorigenesis, angiogenesis, metastasis, and drug resistance. Compared with everolimus, cabozantinib has shown statistically significant improvements in the three key efficacy endpoints of overall survival, progression-free survival, and objective response rate in patients with RCC who were previously treated with a VEGFR TKI. Herein, we summarize the translational research and clinical development that led to approval of cabozantinib as second-line therapy in RCC.
AB - Clear cell renal cell carcinoma (RCC) is characterized by inactivation of the von Hippel-Lindau (VHL) tumor suppressor gene. VHL loss drives tumor angiogenesis and accounts for the clinical activity of VEGF receptor (VEGFR) tyrosine kinase inhibitors (TKIs), the first-line standard of care for advanced RCC. Within the last year, three new second-line treatments have received FDA approval for use after anti-angiogenic therapy: the immune checkpoint inhibitor nivolumab, the TKI cabozantinib, and the combination of the TKI lenvatinib and the mTOR inhibitor everolimus. Cabozantinib inhibits VEGFRs, MET, and AXL, kinases that promote tumorigenesis, angiogenesis, metastasis, and drug resistance. Compared with everolimus, cabozantinib has shown statistically significant improvements in the three key efficacy endpoints of overall survival, progression-free survival, and objective response rate in patients with RCC who were previously treated with a VEGFR TKI. Herein, we summarize the translational research and clinical development that led to approval of cabozantinib as second-line therapy in RCC.
KW - AXL
KW - Angiogenesis
KW - Cabozantinib
KW - MET
KW - RCC
KW - Renal cell carcinoma
KW - VEGF receptor
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U2 - 10.1007/s11912-017-0566-9
DO - 10.1007/s11912-017-0566-9
M3 - Review article
C2 - 28247252
AN - SCOPUS:85014415543
SN - 1523-3790
VL - 19
JO - Current oncology reports
JF - Current oncology reports
IS - 2
M1 - 14
ER -