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35P ABACUS trial: Abiraterone acetate in the management of Cushing’s syndrome associated to adrenocortical carcinoma

2024; Elsevier BV; Volume: 9; Linguagem: Inglês

10.1016/j.esmoop.2024.102424

2059-7029

D. Cosentini, Soraya Puglisi, S. Grisanti, Valentina Basile, M. Laganà, Vittorio Ferrari, A. Abate, Anna Calabrese, E. Rossini, Guido Alberto Massimo Tiberio, A. Pia, Sandra Sigala, Massimo Terzolo, Alfredo Berruti,

Cancer, Hypoxia, and Metabolism

Adrenocortical carcinomas (ACC) are often associated with cortisol and/or androgen hypersecretion. Metirapone and osilodrostat are used for syndrome control despite they induce androgen levels increase. Abiraterone acetate (AA) is an irreversible inhibitor of 17α-hydroxylase/C17, 20-lyase (CYP17) that blocks the adrenal synthesis of cortisol and androgens. The aim of this study was to assess the efficacy of AA in ACC patients with Cushing's syndrome. ABACUS (NCT 03145285) is a phase II trial aiming to assess the activity of AA in normalizing 24-h urinary free cortisol (UFC) excretion within 1 month from treatment start in two cohorts of patients (I: pretreated patients; II: mitotane-naïve patients). Secondary endpoints were to assess: the activity of AA in attaining 50% reduction of 24-h UFC excretion; AA safety. 15 ACC patients, 7 in cohort I and 8 in cohort II, were treated with AA. In 8 patients, multiple steroid secretion was found. Overall, median 24-h UFC (measured by gas-mass spectrometry) was 368 μg/24h (121-7422) at baseline and 94 μg/24h (20-1793) at end of treatment (p=0.01). A normalization of 24-h UFC was obtained in 8 patients (53%), 57% in cohort I and 50% in cohort II. Androgen were also significantly reduced by AA treatment in patients with multiple secretion. In cohort I, a >50% decrease in 24-h UFC was seen in 7 patients (100%) with a median time to effect of 22 days (14-163). After AA, 6 patients received a further line of chemotherapy with a median OS of 5.4 months (0.9-23.2). In cohort II, a >50% decrease in 24-h UFC was seen in 6 patients (75%) with a median time to effect of 16 days (9-29). After AA, 6 patients received at least one line of chemotherapy and 1 patient underwent abdominal surgery, the median OS was 5.8 months (0.9-76). At the end of AA treatment all patients experienced syndrome relapse. AA was well tolerated. Only 1 patient developed a drug-related toxicity (G2 transaminitis), reversible with AA interruption. The results of this proof-of-concept study show that AA is a promising drug to control both cortisol and androgen excess sustained by ACC. Short duration of the study does not allow us to obtain information on long term drug efficacy.