TY - JOUR
T1 - Objective Response and Prolonged Disease Control of Advanced Adrenocortical Carcinoma with Cabozantinib
AU - Kroiss, Matthias
AU - Megerle, Felix
AU - Kurlbaum, Max
AU - Zimmermann, Sebastian
AU - Wendler, Julia
AU - Jimenez, Camilo
AU - Lapa, Constantin
AU - Quinkler, Marcus
AU - Scherf-Clavel, Oliver
AU - Habra, Mouhammed Amir
AU - Fassnacht, Martin
PY - 2020/5/1
Y1 - 2020/5/1
N2 - 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.
AB - 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.
KW - ACC
KW - adrenal cancer
KW - cabozantinib
KW - tyrosine kinase inhibitors
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U2 - 10.1210/clinem/dgz318
DO - 10.1210/clinem/dgz318
M3 - Article
C2 - 31900481
SN - 0021-972X
VL - 105
JO - The Journal of clinical endocrinology and metabolism
JF - The Journal of clinical endocrinology and metabolism
IS - 5
ER -