Abstract OT1-1-09: Opti-HER HEART: A prospective, multicenter, single-arm, phase II study to evaluate the safety of neoadjuvant liposomal doxorubicin plus paclitaxel, trastuzumab, and pertuzumab in patients with operable HER2-positive breast cancer.
Authors: Gavilá J , Llombart A , Guerrero A , Ruiz A , Guillem V 
Published: August 2014

Abstract
Background: In recent years, the concomitant use of two anti-HER2 therapies has been generating great expectations. Of note, despite the high activity reported by several studies, none has ever included a chemotherapeutic regimen with anthracyclines. The therapeutic value of anthracyclines in HER2-positive breast cancer (BC) has been well established. However, the feasibility of their combination with trastuzumab is still controversial. Liposomal anthracyclines, on the other hand, may offer a safer alternative. Of note, in our institutional experience using a regimen of liposomal doxorubicin plus weekly paclitaxel and trastuzumab as standard neoadjuvant therapy for stage II-III breast cancer (BC) patients reach a pathological complete response (pCR) rate of 65%, without any grade 3/4 cardiac toxicity.
Trial Design: This study seeks to optimize the treatment of patients with operable HER2-positive BC, while minimizing cardiac risk, by combining dual anti-HER2 blockade plus a taxane and a liposomal anthracycline. In this single-arm, phase II clinical trial, patients will receive neoadjuvant therapy for six 21-day cycles. Regimen consists of: trastuzumab 4 mg/kg loading dose on Day 1 of Cycle 1, then 2 mg/kg on Days 8 and 15 and on Days 1, 8, and 15 of subsequent cycles; pertuzumab 840 mg loading dose on Day 1 of Cycle 1, then 420 mg on Day 1 of the following cycles; liposome-encapsulated doxorubicin 50 mg/m2 on Day 1 of each cycle; and, paclitaxel 80 mg/m2 on Days 1, 8, and 15 of each cycle. ECG will be performed at baseline and every planned visit. Left ventricular ejection fraction (LVEF) decline will be assessed at baseline, weeks 6 and 12, before surgery, and every 3 months thereafter during the adjuvant period, for a total of 12 months. In order to assess biomarkers of cardiac injury, blood samples will be collected at the same time points. An initial safety run-in phase is included, in which the first ten enrolled patients undergo an intensified safety monitoring for cardiac and hematological adverse events.
Eligibility: Female patients 18–74 years old with primary HER2-positive invasive breast cancer eligible for definitive surgery, with adequate cardiac function.
Specific aims: The primary objective is to assess cardiac safety, measured by the incidence of symptomatic cardiac events and by asymptomatic LVEF decline. Secondary objectives include efficacy, breast conservation rate, additional safety and tolerability, and predictive biomarkers of cardiotoxicity.
Statistical methods: Assuming that the incidences of cardiac events with regimens containing anti-HER2 agents are 3% for symptomatic and 15% for asymptomatic, 83 patients will be required to reject the null hypothesis with 80% confidence. Additionally, efficacy will be evaluated by pCR rates.
Target accrual: Recruitment started in September 2012 and will include 83 patients across 20 sites in Spain. Trastuzumab and pertuzumab are kindly provided by Roche. The trial is supported by a grant from TEVA.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr OT1-1-09.