Immunotherapy: A new standard in the treatment of metastatic clear cell renal cell carcinoma

Table 1 Poor prognostic factor

Poor prognostic factor	MSKCC	IMDC
Time from diagnosis to treatment	< 12 mo	< 12 mo
Hemoglobin	< lower limit of normal	< lower limit of normal
Corrected serum calcium	> 10 mg/dl (2.5 mmol/L)	> upper limit of normal
Karnofsky performance score	< 80%	< 80%
Neutrophil count	/	> upper limit of normal
Platelet count	/	> upper limit of normal
Lactate dehydrogenase	> 1.5 x upper limit of normal	/
Good risk	0 risk factor	0 risk factor
Intermediate risk	1 or 2 risk factors	1 or 2 risk factors
Poor risk	3, 4 or 5 risk factors	3, 4, 5 or 6 risk factors

MSKCC: Memorial Sloan Kettering Cancer Center; IMDC: International mRCC Database Consortium.

Table 2 Results of phase 3 studies in first line treatment of patients with metastatic clear cell renal cell cancer

Drug/Study	No. of patients	Follow-up (mo)	PFS (mo)	OS (mo)	ORR, %	Ref.
Nivolumab/Ipilimumab vs Sunitinib (Checkmate 214)	1096	48	ITT 12.2 vs 12.3; HR 0.89; I/P risk 11.2 vs 8.3; HR 0.74	ITT NR vs 38.4; HR 0.69; I/P risk 48.1 vs 26.6; HR 0.65; F risk; HR 0.93	ITT 39.1 vs 32.4; I/P risk 41.9 vs 26.8; F risk 29.6 vs 51.6	[24]
Pembrolizumab/Axitinib vs Sunitinib (Keynote 426)	861	27	ITT 15.4 vs 11.1; HR 0.71; P < 0.0001	ITT NR vs 35.7; HR 0.68; P = 0.0003	ITT 60 vs 40	[39]
Avelumab/Axitinib vs Sunitinib (Javelin 101)	560	13	ITT 13.3 vs 8; HR 0.69; P < 0.0001; PD-L1 + 13.8 vs 7; HR 0.62; P < 0.0001	ITT NR; HR 0.80; P = 0.0392; PD-L1 + NR; HR 0.83; P = 0.1301	ITT 52.5 vs 27.3; PD-L1 + 55.9 vs 27.3	[44]
Nivolumab/Cabozantinib vs Sunitinib (Checkmate 9ER)	651	18.1	ITT 16.6 vs 8.3; HR 0.51; P < 0.0001	ITT NR vs NR; HR 0.60; P = 0.0010	ITT 55.7 vs 27.1	[45]
Pembrolizumab/Lenvatinib vs Everolimus/Lenvatinib vs Sunitinib (Clear/Keynote 581)	1069	26.6	ITT Pembro/lenva vs sunitinib 23.9 vs 9.2; HR 0.39; P < 0.000; Everolimus/lenva vs sunitinib; 14.7 vs 9.2; HR 0.65; P < 0.0001	ITT Pembro/lenva vs sunitinib NR vs NR; HR 0.66; P = 0.005; Evero/lenva vs sunitinib NR vs NR; HR 1.15; P = 0.30	ITT Pembro/lenva vs Evero/lenva vs sunitinib; 71% vs 53.5% vs 36.1%	[41]

Table 3 Results of checkpoint inhibitors in treatment of patients with metastatic clear cell renal cell cancer

Drug/Study	Phase	Indication	Follow-up	Results	Ref.
Pembrolizumab (Keynote 427)	II	mnccRR	11	ITT ORR 24.8%; ORR Papillary vs phromophobe vs unclasified 25.4% vs 9.5% vs 34.6%; 12 mo PFS 22.8%; 12 mo OS 72%	[50]
Nivolumab (Checkmate 374)	IIIb/IV	mnccRR	11	ITT; OS 16,3 mo; PFS 2,2 mo; ORR 13,6%	[51]
Atezolizumab/Cabozantinib (Cosmic 021)	Ib	mnccRR	9,2	ITT ORR 33%	[52]
Durvalumab/Savolitinib (Calypso)	Ib/II	mnccRCC-papillaryuntreated or previously treated	8,9	ITT; ORR 27%; PFS 3,3 mo; Untreated ORR 29%; PFS 12,2	[53]