Table 1.

FDA-Approved systemic therapies for the treatment of metastatic renal cell carcinoma.

Therapy	FDA Approval	Treatment line	Mechanism of action	Route	Comparator arm	Primary endpoint
Interleukin-2	May-92	First	Cytokine immunotherapy	IV	Phase II- none	ORR
Sorafenib	Dec-05	Cytokine failure	VEGFR, PDGFR, RET, KIT Inhibitor	Oral	Placebo	OS
Sunitinib	Jan-06	First	VEGFR, PDGFR inhibitor	Oral	IFN-α	PFS
Temsirolimus	May-07	First	mTOR inhibitor	IV	IFN-α	OS
Everolimus	Mar-09	VEGFR failure	mTOR inhibitor	Oral	Placebo	PFS
Bevacizumab + IFN-α	Jul-09	First	Anti-VEGF monoclonal antibody	IV + SC	IFN-α ± placebo	OS
Pazopanib	Oct-09	First or cytokine failure	VEGFR, PDGFR, KIT inhibitor	Oral	Placebo	PFS
Axitinib	Jan-12	Second	VEGFR inhibitor	Oral	Sorafenib	PFS
Nivolumab	Nov-15	Second	Anti-PD1 monoclonal antibody	IV	Everolimus	OS
Cabozanitinib	Apr-16	Second	VEGFR, MET, AXL inhibitor	Oral	Everolimus	PFS
Lenvatinib + Everolimus	May-16	Second	VEGFR, FGFR, PDGFR, RET, KIT inhibitor, mTOR inhibitor	Oral	Everolimus or Lenvatinib	PFS
Axitinib + Pembrolizumab	Apr-19	First	VEGFR, anti-PD1 monoclonal antibody	Oral (Axitinib),	Sunitinib	ORR, PFS
				IV (Pembrolizumab)
Cabozanitinib + Nivolumab	Jan-21	First or cytokine failure	VEGFR, MET, AXL inhibitor, Anti-PD1 monoclonal antibody	Oral (Cabozanitinib),	Sunitinib	ORR, PFS
				IV (Nivolumab)
Lenvatinib + Pembrolizumab	Aug-21	First	VEGFR, FGFR, PDGFR, Anti-PD1 monoclonal antibody	Oral (Lenvatinib),	Sunitinib or Lenvatinib/Everolimus	ORR, PFS
				IV (Pembrolizumab)
Ipilimumab + Nivolumab	Apr-18	First	Anti-CTLA-4 monoclonal antibody, Anti-PD1 monoclonal antibody	IV	Sunitinib	ORR, OS, PFS
Axitinib + Avelumab	May-19	First	VEGFR inhibitor, Anti-PDL1 monoclonal antibody	IV (Avelumab),	Sunitinib	OS
				oral (Axitinib)
Tivozanib	Mar-21	Subsequent	TKI	Oral	Sorafenib	PFS

IV, intravenous; ORR, objective response rate; OS, overall survival; PFS, progression-free survival; SC, subcutaneous.

Adapted and modified from Shinder, B. M., Rhee, K., Farrell, D. et al. Surgical Management of Advanced and Metastatic Renal Cell Carcinoma: A Multidisciplinary Approach. Front Oncol, 7: 107, 2017. This is an open access article distributed under the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/).