An Evaluation of Cabozantinib for the Treatment of Renal Cell Carcinoma: Focus on Patient Selection and Perspectives

Figures & data

Table 1 European Recommendation of Systemic First and Second Line Treatment of ccRCC^26–38

	Favorable IMDC Risk Group	Intermediate and Poor IMDC Risk Groups
First line recommended ICI based therapy	Axitinib Pembrolizumab
	Lenvatinib Pembrolizumab
	Cabozantinib Nivolumab
		Nivolumab Ipilimumab
First line alternatives When ICI based therapy is contraindicated or not available	Sunitinib
	Pazopanib
	Tivozanib	Cabozantinib
Second line VEGFR systemic therapy that has not been given previously	Axitinib Cabozantinib Pazopanib Sunitinib Tivozanib Lenvatinib-Everolimus

Table 2 Summary of Efficacy of the Combination in 1st Line

	KEYNOTE 426^Citation34	CLEAR^Citation37	CheckMate 9ER^Citation35,Citation36	CheckMate 214^Citation32
Treatment option	Axitinib + Pembrolizumab	Lenvatinib + Pembrolizumab	Cabozantinib + Nivolumab	Nivolumab + Ipilimumab
Comparative arm	Sunitinib	Sunitinib	Sunitinib	Sunitinib
Primary endpoint	OS and PFS	PFS	PFS	OS and PFS
Median PFS (months)	15.4 vs 11.1 HR 0.71 p<0.0001*	23.9 vs 9.2 HR 0.39 p<0.001*	16.6 vs 8.3 HR 0.51 p<0.0001*	11.6 vs 8.4 HR 0. 82 p=0.03*
Median OS (months)	Not reached vs 35.7 HR 0.68 p<0.001*	Not reached vs not reached HR 0.66 p=0.005**	Not reached vs not reached HR 0.60 p=0.0010**	Not reached vs 26HR 0.63 p<0.001*

Notes: *Primary or coprimary endpoint. **Secondary endpoint.

Table 3 Summary of the Incidence of Drug Interruption in Patients Treated with Cabozantinib, Nivolumab, or with First-Line Combination Therapies

Agents (Trial)	Setting	Incidence of Interruption (%)	Reference
Cabozantinib (METEOR)	L2+	9	Choueiri NEJM 2015^Citation13
Ipilimumab+Nivolumab (Checkmate 214) ITT	L1	22.1	Motzer NEJM 2021^Citation32
Axitinib+Pembrolizumab (Keynote 426)	L1	25.9 -21%pembrolizumab only	Rini NEJM 2019^Citation34
		-20% axitinib only
		-7% both
Cabozantinib + nivolumab (Checkmate 9ER)	L1	19.7  -6.6% nivolumab only  -7.5% cabozantinib onlyseul  -5.6% both	Choueiri NEJM 2021^Citation35
Lenvatinib + Pembrolizumab (CLEAR)	L1	37.2  –28.7% pembrolizumab  -25.6% lenvatinib onlyseul  -13.4% both	Motzer NEJM 2021^Citation37

Note: L, treatment line.

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