Trilostane, an effective signal transduction inhibitor for advanced ER+ve and ER-ve post-menopausal breast cancer

Abstract

540 Background: Acquired endocrine resistance to both SERMs and AIs, is a major clinical problem and a leading cause of treatment failure in post menopausal women with advanced breast cancer. Trilostane (Modrenal) has been shown to modulate binding of estrogen to both estrogen receptor alpha (ERa) and estrogen receptor beta (ERβ) and block cell proliferation in breast cancer cells mediated through both ERE and AP1-dependent pathways. Methods: A total of 714 post-menopausal women with assessable progressing advanced breast cancer were treated with trilostane in eleven centers world-wide. All patients had received prior endocrine and/or chemotherapy. Results: Of the 714 patients, 616 (86%) were known or assumed to be ER+ and of these, 164 (27%) had an objective response (OR = CR + PR = 3 mths) and a further 65 (10%) had disease stabilisation (DS = 6 mths), giving an overall clinical benefit rate (CBR) of 37%. Within this ER+ cohort, 453 patients received trilostane for >12 weeks and achieved an OR of 36% and a CBR of 55%. In the ER- cohort (=15 fmol/mg cytosol protein), the CBR was 18% for all patients and 29% in those receiving trilostane for >12 weeks. Chemotherapy given prior to trilostane therapy affected the response rate: 42% (170/408) patients achieved a CBR with trilostane when previously exposed to other endocrine therapies only; compared to 25% (77/306) patients achieving a CBR with trilostane if previously treated with chemotherapy. Discussion: Trilostane is an effective endocrine agent in advanced breast cancer and, because of its unique mode of action, can also be used in patients with acquired endocrine resistance. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bioenvision Limited Bioenvision Limited