Ravi Kumar1, Anil Kapoor. 1. aDivision of Urology, Department of Surgery, The Ottawa Hospital, University of Ottawa, Ottawa bDivision of Urology, Department of Surgery, Juravinski Cancer Centre, McMaster University, Hamilton, Ontario, Canada.
Abstract
PURPOSE OF REVIEW: Targeted therapies have recently replaced cytokine treatments as the gold standard for management of metastatic renal cell carcinoma (mRCC). Currently approved treatments include the tyrosine kinase inhibitors sunitinib, pazopanib, axitinib, sorafenib, cabozantinib and lenvatinib; the vascular endothelial growth factor (VEGF) inhibitor bevacizumab; the mammalian target of rapamycin (mTOR) inhibitors everolimus and temsirolimus; and the immunologic nivolumab. The purpose of this review is to provide an updated analysis of the clinical data supporting the use of these agents in the first-line and second-line setting. RECENT FINDINGS: In the first-line setting, pazopanib may be better tolerated than sunitinib, an individualized dosing sunitinib regimen based on toxicity might improve survival and cabozantinib appears to be an emerging option. In the second-line setting, three new therapies (cabozantinib, lenvatinib/everolimus and nivolumab) have shown superiority against everolimus, the previous standard therapy. The International Metastatic RCC Database Consortium prognostic model may be useful in guiding the selection of subsequent therapy and patients eligible for metastasectomy. SUMMARY: Targeted therapies are the standard treatment for mRCC. Despite advancements in survival, progression-free survival and tolerability, these targeted therapies remain largely noncurative. Further characterization of the RCC oncogenic pathway, and the ongoing clinical trials should help optimize the management of mRCC.
PURPOSE OF REVIEW: Targeted therapies have recently replaced cytokine treatments as the gold standard for management of metastatic renal cell carcinoma (mRCC). Currently approved treatments include the tyrosine kinase inhibitors sunitinib, pazopanib, axitinib, sorafenib, cabozantinib and lenvatinib; the vascular endothelial growth factor (VEGF) inhibitor bevacizumab; the mammalian target of rapamycin (mTOR) inhibitors everolimus and temsirolimus; and the immunologic nivolumab. The purpose of this review is to provide an updated analysis of the clinical data supporting the use of these agents in the first-line and second-line setting. RECENT FINDINGS: In the first-line setting, pazopanib may be better tolerated than sunitinib, an individualized dosing sunitinib regimen based on toxicity might improve survival and cabozantinib appears to be an emerging option. In the second-line setting, three new therapies (cabozantinib, lenvatinib/everolimus and nivolumab) have shown superiority against everolimus, the previous standard therapy. The International Metastatic RCC Database Consortium prognostic model may be useful in guiding the selection of subsequent therapy and patients eligible for metastasectomy. SUMMARY: Targeted therapies are the standard treatment for mRCC. Despite advancements in survival, progression-free survival and tolerability, these targeted therapies remain largely noncurative. Further characterization of the RCC oncogenic pathway, and the ongoing clinical trials should help optimize the management of mRCC.
Authors: Rola M Saleeb; Mina Farag; Zsuzsanna Lichner; Fadi Brimo; Jenni Bartlett; Georg Bjarnason; Antonio Finelli; Fabio Rontondo; Michelle R Downes; George M Yousef Journal: Mol Oncol Date: 2018-08-23 Impact factor: 6.603