Evaluating the efficacy of cabozantinib in patients with advanced renal cell carcinoma with bone metastasis: An open-label phase 2 study.

535 Background: Bone metastasis negatively impacts patients with advanced renal cell carcinoma (aRCC), leading to poor prognosis and quality of life. Some tyrosine kinase inhibitors, including cabozantinib, have been used as standard care for aRCC. However, there have been no reports demonstrating the effects of cabozantinib on bone metastasis. Here, we report the clinical effects of cabozantinib on bone metastasis in patients with aRCC. Methods: Patients with aRCC who had at least one measurable bone target lesion were enrolled. Patients received cabozantinib 60 mg once daily until disease progression or intolerable toxicity. The primary endpoint was objective response rate (ORR) of bone target lesions based on independent review committee (IRC) assessment using the MD Anderson Cancer Center (MDA) criteria, which are the response criteria specific to bone metastases. Key secondary endpoints included disease control rate (DCR), bone metastasis-free survival (BMFS), progression-free survival (PFS), overall survival (OS), frequency of symptomatic skeletal events (SSE) and safety. Results: In total, 31 patients were enrolled, with a median age of 70.0 years, and most patients (77.4%) had a history of systemic treatments for aRCC. All patients had bone metastasis. The ORR of bone target lesions by IRC-assessed MDA criteria was 6.5% (90% CI: 1.2–18.9), with a disease control rate (DCR) of 90.3% (90% CI: 76.8–97.3). No progressive disease was observed. The median BMFS was not reached (95% CI: 11.5–NR). The median PFS and OS were 11.9 (95% CI: 5.7–NR) months and 24.9 (95% CI: 19.1–NR) months, respectively. Three patients (9.7%) experienced SSE. No new safety concerns were identified. Conclusions: Cabozantinib demonstrated favorable clinical effects on bone metastasis in patients with aRCC, as suggested by a high DCR. Our results may provide useful insights for selecting optimal treatments for the management of aRCC with bone metastasis. Clinical trial information: jRCTs031210220 .