TY - JOUR
T1 - Phase II Study of Dehydroepiandrosterone in Androgen Receptor-Positive Metastatic Breast Cancer
AU - Pietri, Elisabetta
AU - Massa, Ilaria
AU - Bravaccini, Sara
AU - Ravaioli, Sara
AU - Tumedei, Maria Maddalena
AU - Petracci, Elisabetta
AU - Donati, Caterina
AU - Schirone, Alessio
AU - Piacentini, Federico
AU - Gianni, Lorenzo
AU - Nicolini, Mario
AU - Campadelli, Enrico
AU - Gennari, Alessandra
AU - Saba, Alessandro
AU - Campi, Beatrice
AU - Valmorri, Linda
AU - Andreis, Daniele
AU - Fabbri, Francesco
AU - Amadori, Dino
AU - Rocca, Andrea
N1 - Publisher Copyright:
© AlphaMed Press; the data published online to support this summary are the property of the authors
PY - 2019/6
Y1 - 2019/6
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85059118003&partnerID=8YFLogxK
U2 - 10.1634/theoncologist.2018-0243
DO - 10.1634/theoncologist.2018-0243
M3 - Article
SN - 1083-7159
VL - 24
SP - 743-e205
JO - Oncologist
JF - Oncologist
IS - 6
ER -
