ECE2022 Oral Communications Oral Communications 2: Adrenal and Cardiovascular Endocrinology 1 (6 abstracts)
Activity of abiraterone acetate in the management of cushing syndrome associated to advanced adrenocortical carcinoma: results of the ABACUS trial
Soraya Puglisi 1 , Deborah Cosentini 2 , Salvatore Grisanti 2 , Vittoria Basile 1 , Marta Laganà 2 , VittorioDomenico Ferarri 2 , Andrea Abate 3 , Anna Calabrese 1 , Elisa Rossini 3 , Paola Perotti 1 , Laura Saba 1 , Anna Pia 1 , Sandra Sigala 3 , Alfredo Berruti 2 & Massimo Terzolo 1
1Internal Medicine, Department of Clinical and Biological Sciences, San Luigi Hospital, University of Turin, Orbassano, Italy; 2Medical Oncology, Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, Spedali Civili Hospital, University of Brescia, Brescia, Italy; 3Section of Pharmacology, Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy
Background: More than 50% of adrenocortical carcinomas (ACC) in adults are associated with cortisol excess that makes tumor management challenging and has a negative impact on patient outcome. Abiraterone acetate (AA) is an irreversible inhibitor of the 17α-hydroxylase/C17, 20-lyase (CYP17 enzyme) that is used in patients with prostate cancer, in whom it leads to suppression of cortisol and androgens. The aim of this study was to assess the activity of AA to control cortisol excess in patients with advanced ACC and overt Cushing syndrome.
Methods: We designed the phase II trial ABACUS (NCT 03145285) whose primary endpoint was normalization of 24-h urinary free cortisol (UFC) excretion within 1 month from treatment start. Inclusion criteria were histologically proven ACC, locally advanced or metastatic disease, and Cushing syndrome confirmed by two 24-h UFC >1.5 times the upper normal limit with suppressed ACTH. No concomitant treatment with mitotane or chemotherapy was allowed for the first 4 weeks of the study. AA was given orally at the daily dose of 1000 mg. Data are expressed as median and interquartile range.
Results: From 2017 to 2019, we included 17 patients with ACC (2 stage III, 15 stage IV), 13 women (76%), aged 51 years (18-76), of whom 8 have been heavily pretreated and 9 were treatment naïve. In 8 patients, multiple steroid secretion was found. Patients were treated with AA for 17 days (7-163). Median 24-h UFC was 368 μg/24 h (121-7422) at baseline and 94 μg/24 h (20-1793) at end of treatment (P=0.01). Normalization of 24-h UFC was attained in 8 patients (53%) and a >50% decrement in 11 patients (73%). The median time to effect was 21 days and median 24-h UFC reduction 81.8% (-97.7 - +25.9). Androgen and precursor steroids were also significantly reduced by AA treatment. Cushing Syndrome Score and blood pressure significantly decreased during treatment. In 2 patients, treatment was discontinued for toxicity. Seven patients died of ACC progression during follow-up with an overall survival of 5.4 months (0.5-39.3).
Conclusions: A was able to control rapidly cortisol excess in most patients with a good safety profile. The results of this proof-of-concept study show that AA looks promising and may be viewed as an additional weapon to manage Cushing syndrome in patients with ACC. These findings pose the basis for power calculation and implementation of a prospective long-term study to establish AA efficacy in patients with a steroid-secreting ACC.
Volume 81
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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