Table 1.

Summary of pivotal Phase III trials for targeted therapies in advanced RCC

Agent	MOA	FDA approval	Pivotal trial comparator	Pivotal trial population	Primary endpoint	Outcome	References
Tivozanib	VEGF TKI	Pending	Sorafenib	Treatment naïve; one prior non-VEGF/non-mTORi allowed	PFS	PFS 11.9 months (tivozanib) vs 9.1 months (sorafenib), P = 0.042; treatment naïve subset: 12.7 months vs 9.1 months, P = 0.037	24
Sorafenib	VEGF TKI	Approved	Placebo	Prior cytokine allowed	PFS	PFS 5.5 months (sorafenib) vs 2.2 months (placebo), P < 0.000001	17,18
Sunitinib	VEGF TKI	Approved	IFN	Treatment naïve	PFS	PFS 11 months (sunitinib) vs 5 months (IFN), P = 0.001	13,14
Temsirolimus	mTORi	Approved	IFN Temsirolimus/IFN	Treatment naïve	OS	OS 10.9 months (temsirolimus) vs 7.3 months (IFN), P < 0.001	19
Everolimus	mTORi	Approved	Placebo	One or two prior VEGF TKI	PFS	PFS 4.9 months (everolimus) vs 1.9 months (placebo), P = 0.001	20,21
Bevacizumab/IFN	Monoclonal VEGF Ab	Approved	IFN	Treatment naïve	PFS	AVOREN trial: PFS 10.2 months (bevacizumab/IFN) vs 5.4 months (IFN), P < 0.0001	9–12
						CALGB trial: PFS 8.5 months (bevacizumab/IFN) vs 5.2 months (IFN), P = 0.0001
Pazopanib	VEGF TKI	Approved	Placebo	Treatment naïve or prior cytokine allowed	PFS	PFS 9.2 months (pazopanib) vs 4.2 months (placebo), P < 0.0001	15
Axitinib	VEGF TKI	Approved	Sorafenib	One prior therapy (sunitinib, bevacizumab, cytokine, or temsirolimus) allowed	PFS	PFS 6.7 months (axitinib) vs 4.7 months (sorafenib), P < 0.0001	16

Abbreviations: Ab, antibody; IFN, interferon; mTORi, mammalian target of rapamycin inhibitor; OS, overall survival; PFS, progression-free survival; RCC, renal cell carcinoma; VEGF TKI, vascular endothelial growth factor tyrosine kinase inhibitor; MOA, mechanism of action; FDA, Federal Drug Administration.