Efficacy and Safety of Cabozantinib Rechallenge in Metastatic Renal Cell Carcinoma: A Retrospective Multicentric Study.

Background: Despite metastatic renal cell carcinoma (mRCC) expanded treatment options, disease progression ultimately occurs for most patients. Rechallenge may be a compelling strategy in a refractory setting. Cabozantinib is the standard of care in first and later lines of therapy, but its activity in rechallenge is unknown. Methods: This retrospective study assessed the efficacy and safety of cabozantinib re -challenge, as defined by a second exposure after an interval of >= 3 months without treatment or >= 1 other treatment line, in patients with mRCC. The primary endpoint was median pro-gression-free survival (PFS) at rechallenge. Secondary endpoints included overall survival, objective response rate, and safety at rechallenge. Results: We included 51 mRCC patients who received cabozantinib in a rechallenge setting between 2017 and 2022. Median age at diagnosis was 54 years, 78% were male, 90% had clear cell mRCC, and 92% had prior nephrectomy. 15 patients (29%) were rechallenged after a pause in treatment, whereas 36 (70.6%) had >= 1 other treatment lines between first cabo-zantinib exposure (CABO-1) and rechallenge (CABO-2). Median PFS was 15.1 months (mo, 95% Confidence interval 11.2-22.1) at CABO-1 and 14.4mo (95%CI 9.8-NR) at CABO-2. Median overall survival was 67.6mo for CABO-1 (95% CI 52.2-NR) and 27.4mo for CABO-2 (95%CI 17.2-NR); objective response rate was 70.6% for CABO-1 and 60% for CABO-2. CABO-2 PFS was higher for patients with CABO-1 PFS > 12 months, and for those who discontinued CABO-1 because of toxicity, without statistical significance. There were no unexpected adverse events. Conclusions: Cabozantinib rechallenge is a feasible treatment option with potential clinical benefit for mRCC patients. (c) 2023 Elsevier Ltd. All rights reserved.