Platinum-refractory metastatic urothelial carcinoma is the most common type of bladder cancer. Cabozantinib is a small molecule inhibitor of the tyrosine kinases c-Met and VEGFR2, along with AXL and RET. This study aims to investigate the activity of cabozantinib in patients with platinum-refractory metastatic urothelial carcinoma.

This single-arm, open-label, three-cohort phase 2 trial included a total of 68 patients aged 18 or older with histologically confirmed urothelial carcinoma. The patients were assigned to receive cabozantinib 60 mg orally once daily in 28-day cycles until disease progression or unacceptable toxicity. The primary outcome of the study was the objective response rate (investigator-assessed) as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.

During the median follow-up of 61.2 months, one complete response and seven partial responses were observed, with an objective response rate of 19%. The most commonly occurring grade 3 & 4 adverse events were fatigue (9%), hypertension (7%), proteinuria (6%), and hypophosphatemia (6%). No treatment-related deaths occurred during the trial period.

The research concluded that cabozantinib exhibited single-agent clinical activity in patients with heavily pretreated platinum-refractory metastatic urothelial carcinoma. The treatment had a healthy response rate of 19% and was generally well-tolerated.