Objective Response and Prolonged Disease Control of Advanced Adrenocortical Carcinoma with Cabozantinib.
Adrenal Cortex Neoplasms
/ drug therapy
Adrenocortical Carcinoma
/ drug therapy
Adult
Aged
Anilides
/ therapeutic use
Cohort Studies
Disease Progression
Female
Germany
/ epidemiology
Humans
Male
Middle Aged
Neoplasm Staging
Progression-Free Survival
Pyridines
/ therapeutic use
Registries
Retrospective Studies
Salvage Therapy
Treatment Outcome
United States
/ epidemiology
Young Adult
ACC
adrenal cancer
cabozantinib
tyrosine kinase inhibitors
Journal
The Journal of clinical endocrinology and metabolism
ISSN: 1945-7197
Titre abrégé: J Clin Endocrinol Metab
Pays: United States
ID NLM: 0375362
Informations de publication
Date de publication:
01 05 2020
01 05 2020
Historique:
received:
02
09
2019
accepted:
30
12
2019
pubmed:
5
1
2020
medline:
10
2
2021
entrez:
5
1
2020
Statut:
ppublish
Résumé
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. To investigate the clinical efficacy and safety of CABO monotherapy in ACC patients. Retrospective cohort study. Three referral centers for ACC (Germany, United States). 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. 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.
Sections du résumé
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.
Identifiants
pubmed: 31900481
pii: 5695965
doi: 10.1210/clinem/dgz318
pmc: PMC8204945
pii:
doi:
Substances chimiques
Anilides
0
Pyridines
0
cabozantinib
1C39JW444G
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© Endocrine Society 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
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