Objective Response and Prolonged Disease Control of Advanced Adrenocortical Carcinoma with Cabozantinib
Open Access
- 4 January 2020
- journal article
- research article
- Published by The Endocrine Society in Journal of Clinical Endocrinology & Metabolism
- Vol. 105 (5), 1461-1468
- https://doi.org/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 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.Keywords
Funding Information
- Deutsche Forschungsgemeinschaft (314061271—TRR 205)
- NIH
This publication has 39 references indexed in Scilit:
- Combination of sorafenib and everolimus impacts therapeutically on adrenocortical tumor modelsEndocrine-Related Cancer, 2012
- Phase II study of weekly paclitaxel and sorafenib as second/third-line therapy in patients with adrenocortical carcinomaActa Endocrinologica, 2012
- Mitotane has a strong and a durable inducing effect on CYP3A4 activityActa Endocrinologica, 2011
- Sunitinib inhibits cell proliferation and alters steroidogenesis by down-regulation of HSD3B2 in adrenocortical carcinoma cellsFrontiers in Endocrinology, 2011
- New response evaluation criteria in solid tumours: Revised RECIST guideline (version 1.1)European Journal Of Cancer, 2009
- Limited prognostic value of the 2004 International Union Against Cancer staging classification for adrenocortical carcinomaCancer, 2009
- Adjuvant Mitotane Treatment for Adrenocortical CarcinomaNew England Journal of Medicine, 2007
- Prognostic Parameters of Metastatic Adrenocortical CarcinomaJournal of Clinical Endocrinology & Metabolism, 2007
- Management of patients with adrenal cancer: recommendations of an international consensus conferenceEndocrine-Related Cancer, 2005
- Pathologic Features of Prognostic Significance in Adrenocortical CarcinomaThe American Journal of Surgical Pathology, 1989