Objective Response and Prolonged Disease Control of Advanced Adrenocortical Carcinoma with Cabozantinib

• Published in: The journal of clinical endocrinology and metabolism Vol. 105; no. 5; pp. 1461 - 1468
• Main Authors: Kroiss, Matthias, Megerle, Felix, Kurlbaum, Max, Zimmermann, Sebastian, Wendler, Julia, Jimenez, Camilo, Lapa, Constantin, Quinkler, Marcus, Scherf-Clavel, Oliver, Habra, Mouhammed Amir, Fassnacht, Martin
• Format: Journal Article
• Language: English
• Published: US Oxford University Press 01.05.2020; Copyright Oxford University Press
• Subjects: Adrenal Cortex Neoplasms - drug therapy; Adrenal Cortex Neoplasms - epidemiology; Adrenal Cortex Neoplasms - pathology; Adrenocortical Carcinoma - drug therapy; Adrenocortical Carcinoma - epidemiology; Adrenocortical Carcinoma - pathology; Adult; Aged; Anilides - therapeutic use; Axl protein; Cancer; Chemotherapy; Clinical s; Clinical trials; Cohort Studies; Cytotoxicity; Disease control; Disease Progression; Drug interaction; Female; Germany - epidemiology; Humans; Kidney cancer; Liver cancer; Male; Middle Aged; Neoplasm Staging; Neuroendocrine tumors; Patient outcomes; Progression-Free Survival; Pyridines - therapeutic use; Registries; Retrospective Studies; Salvage Therapy; Targeted cancer therapy; Thyroid carcinoma; Treatment Outcome; United States - epidemiology; Vascular endothelial growth factor; Vascular endothelial growth factor receptor 2; Young Adult; United States; Germany; tyrosine kinase inhibitors; ACC; adrenal cancer; cabozantinib
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/clinem/dgz318

Abstract Background Objective response of advanced adrenocortical carcinoma (ACC) to mitotane and cytotoxic chemotherapy regimen is only ~20% and early tumor progression is frequent. Previous clinical trials with oral multikinase inhibitors were negative, which has been attributed in part to inadvertent drug interaction with mitotane. Cabozantinib (CABO) is an inhibitor of c-MET, vascular endothelial growth factor receptor 2, AXL, and RET and approved for advanced kidney cancer, liver carcinoma after previous sorafenib, and medullary thyroid carcinoma. Objective To investigate the clinical efficacy and safety of CABO monotherapy in ACC patients. Design Retrospective cohort study. Setting Three referral centers for ACC (Germany, United States). Results Sixteen patients (13 female) with progressive ACC received CABO after previous mitotane in 15/16 and 3 (median, range 0-8) further systemic treatments. Prior CABO therapy, mitotane was discontinued in all patients. Mitotane plasma concentration was <2 mg/L in 7/16 patients and discontinued >12 months in 6 additional patients before CABO use. In 4/5 cases with available plasma samples, CABO concentration was in the expected steady-state range. Adverse events of grade 1/2 and 3 were observed in 13 and 3 patients, respectively, and consistent with the known safety profile of CABO. Best response was partial response in 3, stable disease in 5, and progressive disease in 8 patients. Median progression-free and overall survival was 16 and 58 weeks, respectively. Conclusion CABO monotherapy appears to be safe and effective as a monotherapy in advanced ACC after failing prior treatments. Therefore, prospective investigation of CABO in ACC patients is warranted.