Early Clinical Experience with Cabozantinib for Advanced Renal Cell Carcinoma in the UK: Real-World Treatment Pathways and Clinical Outcomes.

Cabozantinib monotherapy is approved in the UK for patients with treatment-naïve 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.

CERES (NCT03696407) was a retrospective study of patients with aRCC who received cabozantinib through the 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).

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 (5.16-7.85) 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 in 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.

Cabozantinib demonstrated clinical activity in this UK real-world aRCC population. The results provide a benchmark for future real-world studies in aRCC.

Clinical genitourinary cancer. 2021 Oct 08 [Epub ahead of print]

Balaji Venugopal, Manon Pillai, Thomas Powles, Philip Savage, Agnieszka Michael, Kate Fife, Bhupinder Klair, Valerie Perrot, Bernadett Szabados

Beatson West of Scotland Cancer Centre, NHS Greater Glasgow and Clyde, UK. Electronic address: ., The Christie NHS Foundation Trust, Manchester, UK., Barts Cancer Institute, Queen Mary University of London, London, UK., Brighton and Sussex University Hospitals NHS Trust, Barry Building, Brighton, UK., Royal Surrey County Hospital NHS Foundation Trust, Guildford, UK., Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK., Ipsen, Slough, UK., Ipsen Pharmaceutical, Boulogne-Billancourt, Île-de-France, France.