Abstract
This retrospective study. CERES (NCT03696407), describes early clinical experience with cabozantinib in patients with advanced renal cell carcinoma (aRCC) enrolled in the UK managed access programme (MAP). Cabozantinib demonstrated clinically meaningful activity in all patients across multiple lines of therapy. Charlson Comorbidity Index score warrants further investigation as a prognostic/predictive marker. Our results provide a benchmark for future real-world studies in aRCC.
Background: Cabozantinib monotherapy is approved in the UK for patients with treatment-naive intermediate-or poor-risk advanced renal cell carcinoma (aRCC), or patients who received prior vascular endothelial growth factor-targeted therapy. Data are limited on the real-world use of cabozantinib for aRCC. Patients and Methods: CERES (NCT03696407) was a retrospective study of patients with aRCC who received cabozantinib through he UK managed access programme (MAP; August 2016-July 2017), at which time cabozantinib had European regulatory approval for second- or later-line use only. The study objectives were to characterize aRCC treatment patterns and evaluate cabozantinib effectiveness. Outcomes were stratified by cabozantinib treatment line, MAP treatment date (months 0-7 vs. 8-12) and (post hoc) Charlson Comorbidity Index (CCI; >= 6 vs. < 6). Results: Of 100 patients included, 99% had stage IV disease, 63% had a CCI >= 6 and 81% had an Eastern Cooperative Oncology Group Performance Status 0-1. Median (range) duration of follow-up was 10.8 (0.4-33.5) months. Cabozantinib was administered as second-line, third-line and fourth- or later-line in 41%. 31% and 28% of patients, respectively. Most patients (84%) initiated cabozantinib at 60 mg. Average (range) cabozantinib dose was 45.5 (19.6-59.8) mg/day; 66% of patients had >= 1 dose reduction. Disease progression was the most common reason for discontinuation (65.1%). Median (95% confidence interval) progression-free survival (PFS) and overall survival (OS) were 6.01 (5.16-785) and 10.84 (7.92-16.85) months, respectively. Overall response rate was 34.5%; disease control rate 70.1% and duration of response 6.9 (1.8-26.9) months. No significant differences M survival estimates were observed between treatment line or treatment date subgroups. Total CCI score <= 6 (vs. > 6) was associated with prolonged median PFS and OS. Conclusion: Cabozantinib demonstrated clinical activity in this UK real-world aRCC population. The results provide a benchmark tor future real-world studies in aRCC. (C) 2021 The Authors. Published by Elsevier Inc.