. Author manuscript; available in PMC: 2022 May 1.

Published in final edited form as: Curr Opin Oncol. 2021 May 1;33(3):212–220. doi: 10.1097/CCO.0000000000000721

Table 3:

Clinical trials reporting data on locally advanced or metastatic nccRCC

Treatment	Clinical trial	Mechanism of action	Control	Cohort (Line of therapy)	Endpoint(s)
Sunitinib	SUPAP [44] NCT00541008	VEGFR & PDGFR inhibitor	N/A	pRCC (1^st)	Type I Median PFS: 6.6 mo, 95% CI 2.8–14.8 mo Median OS: 17.8 mo, 95% 5.7–26.1 mo Type II Median PFS: 5.5 mo, 95% CI 3.8–7.1 mo Median OS: 12.4 mo, 95% 8.2–14.3 mo
Everolimus	RAPTOR [68] NCT00688753	mTOR inhibitor	N/A	pRCC (1^st)	Median PFS: 4.1 mo, 95% CI 3.6–5.5 mo Median OS: 21.4 mo, 95% CI 15.4–28.4 mo
Sunitinib	ESPN [45] NCT01185366	VEGFR & PDGFR inhibitor	Everolimus	nccRCC Sarcomatoid RCC	Median PFS: 6.1 vs 4.1 mo, p=0.6 Median OS: 16.2 vs 14.9 mo, p=0.18
Sunitinib	ASPEN [46]	VEGFR & PDGFR inhibitor	Everolimus	nccRCC	PFS: HR1.41, 80% CI 1.03–1.92; p=0.16
Sunitinib (1^st) Everolimus (2^nd)	RECORD-3 [69] NCT00903175	VEGFR & PDGFR inhibitor mTOR inhibitor	Everolimus (1^st) Sunitinib (2^nd)	ccRCC (1^st) nccRCC (1^st)	PFS: HR 1.2, 95% CI 0.9–1.6 Median OS: HR 1.1, 95% 0.9–1.4
Sunitinib	NCT01219751 [70]	VEGFR & PDGFR inhibitor	N/A	nccRCC	Median PFS: 6.4 mo, 95% CI 4.2–8.6 mo 1-year PFS rate: 40%
Foretinib	NCT00726323 [47]	MET & VEGFR2 inhibitor	N/A	pRCC (1^st/2^nd)	ORR: 13.5% Median PFS: 9.3 mo
Crizotinib	CREATE [48] NCT01524926	MET, ALK, ROS1 inhibitor	N/A	Type I pRCC (1^st)	MET+ ORR: 50%, 95% CI 6.8–93.2% 1-yr PFS: 75%, 95% CI 12.8–96.1% 1-yr OS: 75%, 95% CI 12.8–96.1% MET− ORR: 6.3%, 95% CI 0.2–30.2% 1-yr PFS: 27.3%, 95% CI 8.5–50.4% 1-yr OS: 71.8%, 95% CI 41.1–88.4%
Erlotinib	SWOG S0317 [71] NCT00060307	EGFR inhibitor	N/A	pRCC	ORR: 11%, 95% CI 3–24% Median OS: 27 mo, 95% CI 13–36 mo
Tivantinib Erlotinib	SWOG S1107 [72] NCT01688973	MET inhibitor EGFR inhibitor	Tivantinib	pRCC (1^st/2^nd)	RR 0% (Study closed early) Median PFS 2 mo vs 3.9 mo
Savolitinib	SAVOIR [49] NCT03091192	MET inhibitor	Sunitinib	MET-driven, pRCC (1^st/2^nd)	PFS: HR 0.71, 95% CI 0.37–1.36, p=0.31 OS: HR 0.51, 95% CI 0.21–1.17, p=0.11
Savolitinib Durvalumab	CALYPSO [52,53] NCT02819596	MET inhibitor PD-L1 inhibitor	N/A	pRCC (1^st/2^nd)	ORR: 27% Median PFS: 4.9 mo, 95% CI 2.5–12 mo
Atezolizumab Bevacizumab	NCT02724878 [73]	Anti-PD-L1 mAb Anti-VEGF mAb	N/A	nccRCC Sarcomatoid RCC	ORR: 26% nccRCC and 50% sarcomatoid Median PFS: 8.3 mo, 95% CI 5.7–10.9 mo
Ipilimumab Nivolumab	CheckMate 214 [55] Post hoc analysis	Anti-PD1 mAb Anti-CTLA4 mAb	Sunitinib	Sarcomatoid RCC	Median OS: HR 0.45, 95% CI 0.3–0.7, p=0.0004 PFS: HR 0.54, 95% CI 0.33–0.86, p=0.0093 ORR: 60.8% vs 23.1% CR: 18.9% vs 3.1%
Atezolizumab Bevacizumab	IMmotion151 [54] Subgroup analysis	Anti-PD-L1 mAb Anti-VEGF mAb	Sunitinib	Sarcomatoid RCC	PFS: HR 0.52, 95% CI 0.34–0.79 ORR: 49% vs 14% CR: 10% vs 3%

PD-L1: programmed death-ligand 1; VEGFR2: vascular endothelial growth factor receptor 2; EGFR: epidermal growth factor receptor; PDGFR: platelet-derived growth factor receptor; mTOR: mammalian target of rapamycin; PD-1: programmed cell death protein 1; CTLA4: cytotoxic T-lymphocyte associated protein 4; mAb: monoclonal antibody; pRCC: papillary renal cell carcinoma; nccRCC: non-clear cell renal cell carcinoma; ccRCC: clear cell renal cell carcinoma; PFS: progression-free survival; OS: overall survival; ORR: overall response rate; CR: complete response; HR: hazard ratio