Table III. Summary of available efficacy data (divided by age) for approved targeted agents for metastatic renal cell carcinoma (mRCC).

Study	Treatment	Patient population	Age [y; median (range)]a		Efficacy
			overall	by treatment group	outcome: age group (y)	HR (95% CI)
AVOREN
Escudier et al.[5,62]	Bevacizumab + IFN vs placebo + IFN	Treatment-naive mRCC [n = 649]	60–61 (18–82)	Bevacizumab + IFN: 61 (30–82) [n = 327] Placebo + IFN: 60 (18–81) [n = 322]	OS: <65 [n = 410] ≥65 [n = 239] PFSb: <40 [n = 26] 40–64 [n = 384] ≥65 [n = 239]	0.83 (0.65, 1.05) 1.07 (0.80, 1.45) 0.65 (0.28, 1.52) 0.54 (0.43, 0.68) 0.77 (0.58, 1.03)
TARGET
Escudier et al.,[6,106] Eisen et al.[57]	Sorafenib vs placebo	Clear-cell mRCC with one previously failed systemic therapy [n = 903]	59 (19–86)	Sorafenib: 58 (19–86) [n = 451] <70: 57 (19–69) [n = 381] ≥70: 72 (70–86) [n = 70] Placebo: 59 (29–84) [n = 452] <70: 58 (29–69) [n = 407] ≥70: 73 (70–84) [n = 45]	PFS: <70 [n = 788] ≥70 [n = 115]	0.55 (0.47, 0.66) 0.43 (0.26, 0.69)
ARCC
Hudes et al.,[8] Dutcher et al.[64]	Temsirolimus vs IFN vs temsirolimus + IFN	Treatment-naive, advanced RCC with poor prognosis [n = 626]	59 (23–86) <65 [n = 440] ≥65 [n = 186]	Temsirolimus: 58 (32–81) [n = 209] <65: [n = 145] ≥65: [n = 64] IFN: 60 (23–86) [n = 207] <65: [n = 142] ≥65: [n = 65] IFN + temsirolimus: 59 (32–82) [n = 210] <65: [n = 153] ≥65: [n = 57]	OS (temsirolimus vs IFN): <65 [n = 287] ≥65 [n = 129] PFS (temsirolimus vs IFN): <65 [n = 287] ≥65 [n = 129]	0.62 (0.47, 0.82) ND 0.61 (0.47, 0.79) ND
Sunitinib vs IFN
Motzer et al.[2,59]	Sunitinib vs IFN	Treatment naive, clear-cell mRCC [n = 750]	59–62 (27–87)	Sunitinib: 62 (27–87) [n = 375] IFN: 59 (34–85) [n = 375]	PFS: <65 [n = 475] ≥65 [n = 275]	ND ND
CALGB 90206
Rini et al.,[61] Halabi et al.[107]	Bevacizumab + IFN vs IFN	Treatment naive, clear-cell mRCC [n = 732]	61 (55–70)	Bevacizumab + IFN: 61 (56–70)c [n = 369] IFN: 62 (55–70)c [n = 363]	OS: <65 [n = 363] ≥65 [n = 369]	0.80 (0.64, 1.01)d 0.95 (0.75, 1.21)d
VEG105192
Sternberg et al.[3]	Pazopanib vs placebo	Treatment-naive and cytokine-pretreated locally advanced and/or clear-cell mRCC [n = 435]	59 (25–85)	Pazopanib: 59 (28–85) [n = 290] Placebo: 60 (25–81) [n = 145]	PFS: <65 [n = 281] ≥65 [n = 154]	0.41 (0.28, 0.61)e 0.52 (0.33, 0.82)f
RECORD-1
Motzer et al.,[7,108] Osanto et al.[105]	Everolimus vs placebo	VEGFR-TKI-refractory, clear-cell mRCC [n = 416, final analyses; n = 410, interim analyses]	61 (27–85)	Final analyses: Everolimus: 61 (27–85) [n = 277] ≥65: 69 (65–85) [n = 112] ≥70: 74 (70–85) [n = 53] Placebo: 60 (29–79) [n = 139] ≥65: 69 (65–79) [n = 41] ≥70: 73 (70–79) [n = 20] Interim analyses: Everolimus: 61 (27–85) [n = 272] Placebo: 60 (29–79) [n = 138]	Final analyses: PFS [n = 416]: <65 [n = 263] ≥65 [n = 153] Interim analyses: PFS [n = 410]: <65 [n = 259] ≥65 [n = 151]	0.33 (0.21, 0.51)g 0.19 (0.09, 0.37)g 0.32e,h 0.29e,h

^aExcept where otherwise stated.

^bNo significant interaction between age and PFS benefit.

^cInterquartile range.

^dp = not statistically significant.

^ep <0.0001.

^fp = 0.0005.

^gp<0.001.

^hConfidence interval not available.

HR = hazard ratio; IFN = interferon; ND = no data; OS = overall survival; PFS = progression-free survival; TKI = tyrosine kinase inhibitor; VEGFR = vascular endothelial growth factor receptor.