Post‐Marketing Surveillance of the Safety and Effectiveness of Cabozantinib in Japanese Patients With Advanced Renal Cell Carcinoma

OBJECTIVES: This post-marketing surveillance study evaluated the real-world safety and effectiveness of cabozantinib in Japanese patients with advanced renal cell carcinoma (aRCC). METHODS: This prospective, observational study enrolled patients with histologically or cytologically confirmed aRCC across 102 sites in Japan. Patients received cabozantinib as monotherapy or in combination with nivolumab according to approved label regimens and were monitored for 26 weeks. The primary outcome was the incidence of adverse drug reactions (ADRs) related to hepatic failure/dysfunction and pancreatitis. Secondary outcomes included grade 3 or higher ADRs, treatment discontinuation due to ADRs, and investigator-assessed objective response rate (ORR) using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. RESULTS: Of 388 enrolled patients, 385 were included in the analysis (median age, 71.0 years; 70.1% men). Patients receiving monotherapy (n = 322) and those receiving combination therapy (n = 63) reported ADRs related to hepatic failure/dysfunction (16.15% and 25.40%), pancreatitis-related ADRs (2.80% and 4.76%), grade 3 or higher ADRs (24.84% and 38.10%), and ADRs leading to treatment discontinuation (13.98% and 30.16%), respectively. The most common grade 3 or higher ADRs were hypertension (3.73%), reduced appetite (3.11%), and hand-foot syndrome (3.11%) in the monotherapy group, and diarrhea (4.76%) in the combination therapy group. The ORR was 32.9% for patients receiving monotherapy and 41.3% for those receiving combination therapy. CONCLUSIONS: Cabozantinib, as monotherapy or in combination with nivolumab, demonstrated safety and effectiveness in Japanese patients with aRCC in real-world settings, consistent with previous literature. No new safety concerns were identified. These findings support the use of cabozantinib-based regimens in Japanese clinical practice. TRAIL REGISTRATION: Japan Registry of Clinical Trials (JRCT), registration number: jRCT2031210003.