LESSONS LEARNED: The androgen receptor (AR) is present in most breast cancers (BC), but its exploitation as a therapeutic target has been limited.This study explored the activity of dehydroepiandrosterone (DHEA), a precursor being transformed into androgens within BC cells, in combination with an aromatase inhibitor (to block DHEA conversion into estrogens), in a two-stage phase II study in patients with AR-positive/estrogen receptor-positive/human epidermal growth receptor 2-negative metastatic BC.Although well tolerated, only 1 of 12 patients obtained a prolonged clinical benefit, and the study was closed after its first stage for poor activity. BACKGROUND: Androgen receptors (AR) are expressed in most breast cancers, and AR-agonists have some activity in these neoplasms. We investigated the safety and activity of the androgen precursor dehydroepiandrosterone (DHEA) in combination with an aromatase inhibitor (AI) in patients with AR-positive metastatic breast cancer (MBC). METHODS: A two-stage phase II study was conducted in two patient cohorts, one with estrogen receptor (ER)-positive (resistant to AIs) and the other with triple-negative MBC. DHEA 100 mg/day was administered orally. The combination with an AI aimed to prevent the conversion of DHEA into estrogens. The main endpoint was the clinical benefit rate. The triple-negative cohort was closed early. RESULTS: Twelve patients with ER-positive MBC were enrolled. DHEA-related adverse events, reported in four patients, included grade 2 fatigue, erythema, and transaminitis, and grade 1 drowsiness and musculoskeletal pain. Clinical benefit was observed in one patient with ER-positive disease whose tumor had AR gene amplification. There was wide inter- and intra-patient variation in serum levels of DHEA and its metabolites. CONCLUSION: DHEA showed excellent safety but poor activity in MBC. Although dose and patient selection could be improved, high serum level variability may hamper further DHEA development in this setting.
|Data di pubblicazione:||2018|
|Titolo:||Phase II Study of Dehydroepiandrosterone in Androgen Receptor-Positive Metastatic Breast Cancer.|
|Autore/i:||Pietri, E; Massa, I; Bravaccini, S; Ravaioli, S; Tumedei, Mm; Petracci, E; Donati, C; Schirone, A; Piacentini, F; Gianni, L; Nicolini, M; Campadelli, E; Gennari, A; Saba, A; Campi, B; Valmorri, L; Andreis, D; Fabbri, F; Amadori, D; Rocca, A.|
|Digital Object Identifier (DOI):||10.1634/theoncologist.2018-0243|
|Codice identificativo ISI:||WOS:000471906300029|
|Codice identificativo Scopus:||2-s2.0-85059118003|
|Codice identificativo Pubmed:||30591548|
|Citazione:||Phase II Study of Dehydroepiandrosterone in Androgen Receptor-Positive Metastatic Breast Cancer / Pietri, E; Massa, I; Bravaccini, S; Ravaioli, S; Tumedei, Mm; Petracci, E; Donati, C; Schirone, A; Piacentini, F; Gianni, L; Nicolini, M; Campadelli, E; Gennari, A; Saba, A; Campi, B; Valmorri, L; Andreis, D; Fabbri, F; Amadori, D; Rocca, A.. - In: THE ONCOLOGIST. - ISSN 1083-7159. - (2018), pp. 1-1.|
|Tipologia||Articolo su rivista|
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