CABOPRE: Evaluating Perioperative Cabozantinib’s Efficacy and Biomarkers for Cytoreductive Nephrectomy in Advanced Renal Cell Carcinoma

Background/Objectives: Despite advances in metastatic renal cell carcinoma (mRCC), long-term survival is poor and biomarkers are lacking. Optimal integration of cytoreductive nephrectomy (CN) in the current era remains controversial. CABOPRE, the first phase II trial assessing perioperative cabozantinib in mRCC patients eligible for CN, aimed to determine its effects in this setting, integrating tumor outcomes with molecular profiling.

Methods

CABOPRE (NCT06377722) is a multicentre, single-arm, phase II study conducted in Spanish academic hospitals. Patients with resectable metastatic clear cell RCC (ccRCC) eligible for post-treatment CN received perioperative cabozantinib (60 mg/day for 12 weeks; n = 18). The primary endpoint was the objective response rate (ORR) at 12 weeks assessed by RECIST v1.1. Exploratory analyses included longitudinal plasma miRNA and spatial transcriptomic profiling to identify candidate biomarkers. The trial closed early because of slow accrual, after enrolling 18 of 50 planned patients and without completing the 26-patient first stage of the Simon two-stage design; the planned interim analysis was therefore never performed.