Tailored neoadjuvant epirubicin and cyclophosphamide and nanoparticle albumin bound (nab)-paclitaxel for newly diagnosed breast cancer

Abstract

Background: Neoadjuvant chemotherapy for breast cancer allows response to be assessed depending on subtype, and to judge impact of response to therapy on progression-free survival (PFS). Methods: This study enrols women with breast tumours > 2cm and high likelihood of response, to receive Epirubicin 90mg/m2 and Cyclophosphamide 600mg/m2 Q3 weeks x 4 followed by nab-Paclitaxel (125mg/m2 IV days 1, 8, 15 Q4 weeks) for 12 weeks. Trastuzumab Q3 weeks, will be added to nab-paclitaxel in HER2 positive patients. Forty women; 15 HER2 positive, 15 triple negative and 10 patients with Oncotype DX assay Recurrence Score (RS) >25 will be evaluated for response. We will screen 50 hormone positive women to identify 10 with Oncotype DX assay RS ≥25 and the patients with RS <25 will be included as an exploratory cohort to receive neoadjuvant hormonal treatment. The primary endpoint is rate of pathologic Complete Response (pCR) in the breast. In previous studies, Response Rate (RR) ranged from 12 to 30%. Accordingly, we set RR rate for the null hypothesis (uninteresting) at 30% and for the alternative (worthy of further study) at 50% (CI 95%). Forty patients will be evaluated to discern between RR of 30% and 50% (6% type I error and 87% power). If at the end of the study, 17 or more patients achieve pCR, the regimen will be deemed worthy of further study. Secondary end points include rate of breast conservation, safety and tolerability, PFS and a number of translational endpoints using pre- and post-chemotherapy MRIs and tissue. Translational endpoints include determination of NQO1*2 genotype (P187S) status that may predict anthracycline resistance, isolating cancer stem cells, passing fresh tumour to xenograft, implanting tumours, using aptamers to target implanted tumours and targeting breast cancer stem cells with novel agents including cyclin D and histone deacetylatase inhibitors. Current status: Recruitment began April 2013. A total of 20 patients have been enrolled on to the study as of Feb 2014. Clinical trial information: NCT01830244.