Abstract OT1-01-03: A phase II trial of neoadjuvant epirubicin/cyclophosphamide followed by weekly nanoparticle albumin-bound paclitaxel with trastuzumab for HER2-positive breast cancer
Authors: Kodera A , Hirano A , Inoue H , Ogura K , Hattori A , Sakaguchi S , Yukawa H , Matsuoka A , Tanaka N , Kamimura M , Jibiki N , Fujibayasi M , Naritaka Y , Shimizu T 
Published: March 2017

Abstract
Background
Paclitaxel (PTX) is a standard treatment for metastatic breast cancer (MBC) and it is often used as adjuvant and neoadjuvant chemotherapy for patients with early-stage disease. Nanoparticle albumin-bound (Nab)-PTX was also effective in patients with metastatic and early-stage. A comparison of weekly and triweekly nab-PTX regimens suggested that weekly nab-PTX resulted in superior progression-free survival. However, the optimal dose and schedule of weekly nab-PTX have not been determined. The efficacy and tolerability of epirubicin/cyclophosphamide (EC) followed by weekly nab-PTX (125 mg/m2) ± trastuzumab in node-positive breast cancer was determined in our previous trial. A high pathologic complete response (pCR) rate was obtained in HER2-positive patients. However, because nab-PTX administration was frequently postponed and discontinued, the optimal dose needs to be determined. In the previous trial, the median relative dose intensity of nab-PTX was 80% among patients with pCR. Therefore the dose of nab-PTX was reduced by 20% in this newly designed trial.
Trial design
This phase II trial aimed to evaluate the efficacy and toxicity of neoadjuvant EC followed by weekly nab-PTX with trastuzumab in patients with HER2-positive breast cancer. Patients will receive 4 cycles of epirubicin (90 mg/m2) and cyclophosphamide (600 mg/m2) every 3 weeks, followed by 4 cycles of nab-PTX (100 mg/m2) on days 1, 8, and 15, over a 28-day cycle. Fifteen cycles of trastuzumab (2 mg/kg, loading dose: 4 mg/kg) will be added to the nab-PTX regimen.
Eligibility criteria
Surgery and chemotherapy-naïve patients with pathologically confirmed T2-4 N0-3 invasive breast cancer, as diagnosed by core needle biopsy, are included. Eligibility criteria include age 20–70 years, a performance status of 0–2, and adequate organ function.
Specific aims
The primary endpoint is the pCR rate in the breast and axilla. Secondary endpoints include the breast conservation rate, toxicities, relative dose intensities, feasibility, and overall survival. A pCR is defined as the disappearance of invasive cancer cells, including in the axilla; residual intraductal cancer is acceptable.
Statistical methods
The sample size was calculated using the Simon method, with a type I error of 5% and a study power of 80%. The expected rate of pCR is 72% with a threshold pCR rate of 45%. The required number of patients was estimated to be 25.
Present and target accrual
Patient accrual within two medical centers began in May 2014. A final study population of 30 patients is expected (Trial registration: UMIN000013886).
Citation Format: Kodera A, Hirano A, Inoue H, Ogura K, Hattori A, Sakaguchi S, Yukawa H, Matsuoka A, Tanaka N, Kamimura M, Jibiki N, Fujibayasi M, Naritaka Y, Shimizu T. A phase II trial of neoadjuvant epirubicin/cyclophosphamide followed by weekly nanoparticle albumin-bound paclitaxel with trastuzumab for HER2-positive breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr OT1-01-03.