Abstract P6-17-14: Eribulin, trastuzumab, and pertuzumab as first-line therapy for patients with HER2-positive metastatic breast cancer: A multicenter, collaborative, open-label, phase II clinical trial for the SBCCSG-36 investigators
Authors: Inoue K , Ninomiya J , Okubo K , Nakakuma T , Yamada H , Kimizuka K , Higuchi T , Saito T 
Published: May 2019

Abstract
Background: Docetaxel, trastuzumab, and pertuzumab (DTP) therapy is established first-line therapy for patients with HER2-positive metastatic breast cancer (HER2 + MBC). However, the poor tolerability of docetaxel impedes its long-term administration. The safety of eribulin, trastuzumab, and pertuzumab (ETP) therapy for HER2 + MBC has been confirmed in Japan. We examined the primary endpoint—overall response rate, the secondary endpoints—time to treatment failure, progression-free survival, and overall survival, as well as adverse events (AEs) of ETP therapy. (University Hospital Medical Information Network identifier:000021585)
Methods: Eribulin 1.4 mg/m2/day iv (days 1 and 8), trastuzumab 8 mg/kg iv over 90 min (initial dose) and 6 mg/kg iv over 30 min (second and subsequent doses), and pertuzumab 840 mg/body over 60 min (initial dose) and 420 mg/body over 30 min (second and subsequent doses) were administered. Cycles consisting of 2 doses of eribulin and 1-week drug holiday were repeated. Patients were treated with trastuzumab and pertuzumab when AEs developed that did not allow medication continuation by reducing the dose of eribulin. Antitumor effect was assessed according to RECIST version 1.1. and toxicities to CTCAE Japanese version 4.0. All patients provided written informed consent before enrollment. The study protocol was approved by the Institutional or Central Ethics Committee, and the study was conducted in accordance with the Declaration of Helsinki, Good Clinical Practice, and local ethical and legal regulations.
Results: 25 female patients (median age: 57 years [41-75]) were enrolled from April 18, 2016, through November 22, 2017. Twenty-four had performance status (PS) 0, 1 PS 1, 8 stage 4 breast cancer, and 17 metastatic breast cancer. Anthracycline, taxane, and trastuzumab were administered as neoadjuvant and adjuvant pharmacotherapies to 13, 15, and 14 patients, respectively. Primary tumor was positive for estrogen and progesterone receptors in 12 and 6 patients, respectively. Lung, liver, and bone metastases occurred in 9, 9, and 6 patients, respectively. Three (12%), 17 (68%), 1 (4%), 1 (4%), and 2 (8%) patients showed complete response (CR), partial response (PR), long-term stable disease (LSD; stable disease ≥24 weeks), stable disease (SD; stable disease &lt;24 weeks), and progression disease (PD), respectively; 1 (4%) was unassessable because ETP therapy could not be conducted due to the grade 3 infusion reaction of pertuzumab. Major AEs were neutropenia, anemia, fatigue, peripheral neuropathy, alopecia, and anorexia. The overall response rate (CR+PR) was 80.0% (95% confidence interval 59.3-93.2%). The median follow-up was 10.1 months [3.9-21.5]. Six and 3 patients showed tumor deterioration and died of breast cancer, respectively.
Conclusions: Similar to DTP, ETP showed high response rates and good safety as first-line therapy for HER2 + MBC.
Citation Format: Inoue K, Ninomiya J, Okubo K, Nakakuma T, Yamada H, Kimizuka K, Higuchi T, Saito T. Eribulin, trastuzumab, and pertuzumab as first-line therapy for patients with HER2-positive metastatic breast cancer: A multicenter, collaborative, open-label, phase II clinical trial for the SBCCSG-36 investigators [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P6-17-14.