CABOSUN Trial: Overall Survival and Progression Free Survival with Cabozantinib versus Sunitinib as Initial Therapy for Metastatic Renal Cell Carcinoma

25 Oct, 21

Introduction

VEGFR-targeted therapy is the current standard first-line treatment for patients with advanced renal cell carcinoma (RCC). Cabozantinib is an oral inhibitor of MET, AXL, and VEGFR2 that is approved for treatment of patients with advanced RCC after prior antiangiogenic therapy. CABOSUN trial compared cabozantinib versus sunitinib as initial targeted therapy in patients with metastatic RCC of intermediate or poor risk by IMDC criteria.

Aim

To report progression free survival (PFS) and objective response rate (ORR) updated overall survival (OS) for the CABOSUN trial in patients with advanced RCC of intermediate or poor risk.

Patient Profile

Patients with metastatic RCC with a clear-cell component and measurable disease per investigator without previous systemic treatment for RCC

Methods

Study Endpoints

The primary end-point was PFS assessed by investigator.
Secondary end-points were ORR per investigator, OS, and safety. PFS, ORR and best change in tumour target lesions

Results

Progression free survival

Cabozantinib significantly improved PFS compared with sunitinib (Figure 1)

Figure 1: Median PFS with cabozantinib versus sunitinib

PFS based on stratification of factors and MET expression level (Table 1)
- Subgroup analyses of PFS based on MET expression level favored cabozantinib over sunitinib (HR < 1) regardless of MET status

Table 1: Subgroup analyses of PFS per IRC assessment based on the stratification factors and MET expression level

Endpoint	MET positive (n=62)		MET negative (n=69)
	Cabozantinib	Sunitinib	Cabozantinib	Sunitinib
mPFS months	13.8	3.0	6.9	6.1
	(HR 0.32)		(HR 0.67)

Reduction in tumour target lesions by IRC assessment was observed in 63 (80%) of 79 patients with cabozantinib compared with 39 (50%) of 78 patients with sunitinib

Table 2: Tumour Response

Tumour response	Cabozantinib (N=79)	Sunitinib (N=78)
Objective response rate	20%	9%
Best overall response
Confirmed partial response	16 (20%)	7 (9%)
Stable disease	43 (54%)	30 (38%)
Progressive disease	14 (18%)	23 (29%)
Unevaluable or missing	6 (8%)	18 (23%)

Overall Survival

OS analysis showed a HR <1, observationally favouring cabozantinib

Figure 2: Median overall survival

Adverse events

Adverse events of any grade regardless of causality were recorded
- 75 (96%) cabozantinib-treated patients
- 71 (99%) sunitinib-treated patients
The most common adverse events were diarrhoea, hypertension, fatigue, and AST increased with cabozantinib and fatigue, platelet count decreased and diarrhoea with sunitinib.

Table 3: All-causality adverse events

Adverse event	Cabozantinib (N = 78)			Sunitinib (N = 72)
	Grade 1-2	Grade 3	Grade 4	Grade 1-2	Grade 3	Grade 4
Any adverse event	19 (24%)	45 (58%)	8 (10%)	17 (24%)	42 (58%)	5 (7%)
Diarrhoea^a	49 (63%)	8 (10%)	0	31 (43%)	8 (11%)	0
AST increased^a	45 (58%)	1 (1%)	1 (1%)	20 (28%)	2 (3%)	0
Fatigue^a	45 (58%)	5 (6%)	0	37 (51%)	12 (17%)	0
ALT increased^a	39 (50%)	3 (4%)	1 (1%)	20 (28%)	0	0
Decreased appetite	33 (42%)	4 (5%)	0	22 (31%)	1 (1%)	0
Dysgeusia	32 (41%)	0	0	21 (29%)	0	0
Hypertension^a	30 (39%)	22 (28%)	0	17 (24%)	14 (19%)	1 (1%)
Platelet count decreased^a	29 (38%)	1 (1%)	0	36 (50%)	6 (8%)	2 (3%)
PPES^a	27 (35%)	6 (8%)	0	21 (29%)	3 (4%)	0
Anaemia	25 (32%)	1 (1%)	0	31 (43%)	2 (3%)	0
Stomatitis	25 (32%)	4 (5%)	0	17 (24%)	4 (6%)	0
Nausea	23 (29%)	2 (3%)	0	25 (35%)	3 (4%)	0
Weight decreased	22 (28%)	3 (4%)	0	12 (17%)	0	0
Dyspepsia	21 (27%)	0	0	12 (17%)	0	0
Hypothyroidism	18 (23%)	0	0	4 (6%)	0	0
Blood creatinine increased	17 (22%)	2 (3%)	0	13 (18%)	2 (3%)	0
Vomiting	17 (22%)	1 (1%)	0	14 (19%)	2 (3%)	0
Dizziness	16 (21%)	1 (1%)	0	16 (22%)	0	0
Dysphonia	16 (21%)	1 (1%)	0	1 (1%)	1 (1%)	0
Hyperglycaemia	16 (21%)	0	0	7 (10%	4 (6%)	0
Neutrophil count decreased^a	12 (15%)	0	0	22 (31%)	3 (4%)	0
White blood cell count decreased	9 (12%)	0	0	23 (32%)	2 (3%)	0

Adverse events of any grade regardless of causality were recorded for 75 (96%) cabozantinib-treated patients and 71 (99%) sunitinib-treated patients

^a Solicited adverse event.

Conclusion

Cabozantinib treatment demonstrated clinically meaningful and statistically significant prolongation of PFS per IRC compared with sunitinib as initial targeted therapy in patients with advanced RCC in this phase 2 trial
The findings indicated that cabozantinib is a potential treatment option as initial therapy for patients with advanced RCC of intermediate or poor risk

Reference

European Journal of Cancer. 2018);94:115e125