A Phase Ii Trial of Abiraterone Acetate Plus Prednisone in Patients with Molecular Apocrine (Her2-Negative) Locally Advanced or Metastatic Breast Cancer: a Ucbg Study

Background: The molecular apocrine breast cancer subset has recently been identified. These tumours are estrogen receptor (ER) negative but are characterised by the expression of many genes expressed by ER-positive luminal tumours and, interestingly, are androgen receptor (AR) positive. One third of these tumours are HER2-negative. Abiraterone acetate (AA) is a novel, selective, irreversible, and potent inhibitor of CYP17 enzymatic activity that reduces testosterone levels in the blood to undetectable range. Trial design: We are conducting an uncontrolled, open-label, prospective, multicentric, phase II trial to evaluate the clinical activity of AA in patients with molecular apocrine inoperable locally advanced or metastatic breast cancer. Before inclusion, tumour samples (primary or metastatic) from patients presenting with a triple negative cancer are screened centrally for confirmation of ER/PgR/HER2 negativity and assessment of AR positivity. Additionally patients could be chemotherapy naive or have received any number of lines of chemotherapy with measurable or non-measurable disease. Patients receive AA 1,000 mg and prednisone 10 mg daily until progression or unacceptable toxicity. The primary endpoint is the clinical benefit rate (CR + PR + SD ≥ 24 weeks). Secondary objectives include objective response rate, duration of response, overall survival, progression-free survival and safety. The translational research study focuses on identifying AA response biomarkers as well as improving the molecular definition of apocrine breast cancer, and describing the variation of circulating tumour cells levels. The target accrual is 31 patients. This is a single stage design to discriminate between a 15% and 35% clinical benefit (power 80%, Alpha 5%). As of April 2014, 28 French centers are open for enrolment (first site opened since June 2013). 18 centers have registered 59 patients. Of 55 centrally reviewed tumours, 25 (45%) were tested as ER/PgR/HER2 negative and AR positive leading to the inclusion of 19 patients for now. Disclosure: All authors have declared no conflicts of interest.