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

Abstract

e12025

Background: We evaluated tailored neoadjuvant chemotherapy (NAC) with sequential EC followed by nab-Paclitaxel. OncotypeDX assay was used to select women with Hormone Receptor (HR) + early BC. Methods: Between 4/2013 and 1/2015, patients with stage II (T > 2cm) or III BC received 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 was added to nab-paclitaxel in HER2+ patients. The primary cohort consisting of forty women (15 HER2+, 15 triple negative and 10 patients with OncotypeDX assay Recurrence Score ≥ 25) were evaluated for rate of pathologic Complete Response (pCR). Eleven women with HR+ BC and RS < 25 were treated in a separate exploratory cohort of neoadjuvant hormonal treatment. The primary endpoint was rate of pCR in the breast. Response Rate (RR) for the null hypothesis was set at 30% and for the alternative (worthy of further study) at 50% (CI 95%) i.e., if 17 or more patients achieve pCR at the end of the study, the regimen will be deemed worthy of further study. Secondary endpoints include pCR in breast and lymph nodes, rate of breast conservation, toxicity (measured by CTCAE v.4), PFS and a number of translational endpoints using pre- and post-chemotherapy MRIs and tissue analysis. Clinicaltrials.gov #: NCT01830244. Results: Median age was 50 years (34-76) in the primary cohort (n = 40). Clinical stage at diagnosis is outlined in Table 1. Clinical lymph node involvement at diagnosis was confirmed with needle biopsy in 20 out of the 27 patients with N1-3 stage BC. An independent data safety board regularly reviewed study conduct and the chemotherapy regimen was well tolerated with < 10% rate of grade 3 - 4 adverse events. Conclusions: Selection of BC patients for NAC using our NEONAB study approach including use of Oncotype DX in the neoadjuvant setting was feasible with acceptable toxicities. The clinical endpoint including PCR rate in the breast and lymph nodes, toxicity, radiologic response rates and rates of breast conservation will be reported at the annual meeting. Clinical trial information: NCT01830244.

Characteristic No % T stage T2 26 67.5 T3 10 25 T4 3 7.5 cN stage N0 13 32.5 N1 16 40 N2 9 22.5 N3 2 5