Table 1. Studies comparing OS and PFS with VEGF TKI-mTORi versus VEGF TKI-VEGF TKI (HR<1 favors second-line mTORi versus VEGF TKI).

Study	DataSource	InclusionCriteria	mTORiincluded	VEGFTKIincluded	RetrospectiveCohort	Adjustment	Multicenter	N,mTORi	N,VEGFTKI	OS HR(95% CI)a	PFS HR(95% CI)b
Buschet al.2011	Medicalrecords from2 centers inGermany	Progression on first-line VEGF TKI	Everolimus	Sunitinibandsorafenib	Y	Yd	Y	62	46	0.79(0.43, 1.45)	0.86(0.57–1.28)d
Chenet al.2012	US claimsdata	Received sunitinib	Everolimus	Sorafenib	Y	Y	Y	117	65	1.03(0.59, 1.79)	N/A
Henget al.2012c	Internationalregistry(Canada,UnitedStates,Singapore, andDenmark)b	Received first-line VEGF TKI	Everolimusandtemsirolimus	Sunitinibandsorafenib	Y	Yd	Y	277	541	0.84(0.67, 1.06)	1.18(0.92–1.5)d
Wonget al.2013	Nationwidechart reviewin the UnitedStates	Failed first-line VEGF TKI	Everolimus	Sorafenib	Y	Y	Y	233	123	0.65(0.42, 0.99)	0.75(0.53–1.07)
Parket al.2012	Medicalrecords froma singlecenter inSouth Korea	Failed first-line VEGF TKI	Everolimusandtemsirolimus	Sunitinibandsorafenib	Y	Yd	N	42	41	1.71(0.86, 3.4)	1.03(0.62–1.69)d
Goreet al.2013	Multicenter,Australia,Brazil,Canada,Europe,United States	Received first-line sunitinib in a randomized trial	Everolimus,temsirolimus,SirolimusandSGN-75	Sunitinibandsorafenib	Y	N	Y	42	171	1.05(0.71, 1.54)	N/A
Harrisonet al.2012	Multicenter,United States	Patients alive since January 2007 and diagnosed between January 1, 2007, and February 7, 2011	Notspecified	Notspecified	N	N	Y	33	32	3.13 (0.96, 10.22)	N/A
Ruizet al.2013	Single-institution,Spain	Received at least 1 line of target therapy between 2007 and 2011	Everolimusandtemsirolimus	Sunitinib,sorafenib,bevacizumab,pazopanib,axitinibe,dovitinib	Y	N	N	19	34	1.10(0.56, 2.17)	N/A
Buschet al.2013	Medicalrecords from2 centers inGermany	Failure of first-line VEGF TKI	Everolimusandtemsirolimus	Sunitinibandsorafenib	N	Yd	Y	41	62	0.86(0.51, 1.44)	0.76(0.43–1.35)d
Iacovelliet al.2013	Medicalrecords frommultiplecenters inItaly	Patients consecutively treated with 3 targeted therapies	Everolimusandtemsirolimus	Sunitinibandsorafenib	N	Y	Y	95	152	2.59(1.59, 4.22)	N/A
Elaidiet al.2013	Medicalrecords from7 centers inEurope	Received VEGF TKI-VEGF TKI or VEGF TKI-mTORi	Everolimusandtemsirolimus	Sunitinib,sorafenib,pazopanib,axitinibe	Y	Y	Y	123	118	N/A	1.56(1.11–2.22)
Signorovitchet al.2013	Chart review,multicenter,United States	Started second-line targeted therapy in 2010 or later	Everolimusandtemsirolimus	Sunitinib,sorafenib,pazopanib,axitinibe	Y	Y	Y	138	79	N/A	0.74(0.48, 1.15)

CI, confidence interval; HR, hazard ratio; mTORi, mammalian target of rapamycin inhibitor; N/A, not available; OS, overall survival; PFS, progression-free survival; VEGF TKI, vascular endothelial growth factor tyrosine kinase inhibitor.

^aOS HRs and 95% CIs were imputed for Harrison et al. 2012, Gore et al. 2013, and Ruiz et al. 2013.

^bPFS HRs and 95% CIs were imputed for Heng et al. 2012 and Busch et al. 2013.

^cHeng et al. 2012 used prospective data collection. However, the comparative analysis was performed retrospectively.

^dThe PFS results for Busch et al. 2011, Heng et al. 2012, Park et al. 2012, and Busch et al. 2013 were unadjusted. Y in column adjustment refers to the OS results.

^eOnly one patient received axitinib in Elaidi et al. 2013. The number of patients who received axitinib was not reported in Ruiz et al. 2013. The number receiving axitinib was n = 10 in Signorovitch et al. 2013 (personal communication).