Efficacy of cabozantinib and sunitinib for the treatment of intermediate/poor risk renal cell carcinoma based upon UK real-world data

Background

The purpose of this study was to explore the effectiveness of cabozantinib versus sunitinib for the treatment of first-line metastatic renal cell carcinoma in intermediate/poor risk patients.

Materials and methods

Retrospective review of cases between 1 January 2018 and 30 June 2021 across 17 UK centres. Univariable and multivariable Cox proportional hazards modelling to identify prognostic factors. Inverse probability of treatment weighting, to estimate the causal effect of first-line treatment type.

Results

Cabozantinib patients (n = 106) had poorer risk status, less prior nephrectomy, shorter time to therapy, and more clear cell histology than sunitinib patients (n = 218). More sunitinib patients received a second or third line of subsequent treatment (56% and 23% versus 43% and 13%). Though there was no significant difference between treatments in overall survival (OS) or progression-free survival (PFS) across models, the difference in PFS bordered on significant in a multipredictor analysis (benefit in favour of cabozantinib; P = 0.06). When the Kaplan–Meier curves were stratified by risk status (intermediate versus poor), patients had similar OS within the risk groups. PFS appeared to differ with poor risk patients performing better on cabozantinib. Inverse probability of treatment weighting analysis showed little difference from the unadjusted results: OS hazard ratio = 1.119 (95% confidence interval (CI) 0.823-1.521); PFS hazard ratio 0.825 (95% CI 0.636-1.070) for cabozantinib versus sunitinib.

Conclusions

Our results showed no significant difference in either OS or PFS between treatments. Cabozantinib trended towards improved PFS and reduced OS. Decision-making for tyrosine kinase inhibitor monotherapy should consider later-line treatment options. This analysis is of particular relevance as sunitinib is now off-patent meaning that the cost of a course of treatment has considerably reduced.