Abstract OT3-1-04: A phase 2 study of eribulin in combination with pertuzumab and trastuzumab for advanced or recurrent human epidermal growth factor receptor 2 (HER2)-positive breast cancer (SONG-02)
Authors: Abe Hajime , Kamigaki Shunji , Komoike Yoshifumi , Matsunami Nobuki , Nakano Yoshiaki , Tezuka Kenji , Tsurutani Junji , Yamamura Jun , Yamazaki Keiichi 
Published: May 2015

Abstract
Background: Pertuzumab, an anti-HER2 humanized monoclonal antibody that inhibits receptor dimerization, has a mechanism of action that is complementary to that of trastuzumab, and the combination of pertuzumab plus trastuzumab plus taxanes, when used as first-line treatment for HER2-positive metastatic breast cancer, significantly prolonged progression-free survival (PFS). However, in the second and later line treatment of HER2-positive advanced or recurrent breast cancer, it has not settled whether it should be treated with pertuzumab plus trastuzumab plus chemotherapy or with trastuzumab plus chemotherapy. Eribulin mesylate is a non-taxane microtubule dynamics inhibitor that has been proved to prolong the overall survival of advanced or recurrent breast cancer patients compared with the treatment of physician's choice. The benefit of eribulin in combination with trastuzumab for patients with locally recurrent or metastatic HER2-positive breast cancer has been reported. However, the efficacy and safety of eribulin in combination with pertuzumab and trastuzumab for advanced or recurrent HER2-positive breast cancer patients has not been reported. The purpose of this study is to evaluate the efficacy and safety of eribulin in combination with pertuzumab and trastuzumab as second and later line therapy for patients with advanced or recurrent HER2-positive breast cancer.
Trial Design: This is a multicenter single arm phase 2 study for advanced or recurrent HER2-positive breast cancer patients who have experienced progression with anti-HER2 therapy. Patients received eribulin mesylate 1.4mg/m2 administered via intravenous (IV) infusion over 2 to 5 minutes on Days 1 and 8 each 21-day cycle and pertuzumab 840mg/kg IV and trastuzumab 8mg/kg IV over 90 minutes on Day 1 of Cycle 1. Thereafter eribulin mesylate 1.4mg/m2 and pertuzumab 420mg/kg and trastuzumab 6mg/kg was infused each 21-day cycle until disease progression or the appearance of toxic effects that could not be effectively managed. The primary endpoint is PFS of the combination therapy, based on local assessment of response using RECIST 1.1 criteria. Secondary endpoints are overall response rate (ORR), safety and tolerability. In addition, we examine PFS and safety according to the most recent treatment regimen. The study was conducted in accordance with the Declaration of Helsinki (2008), and the protocol and informed consent forms were submitted for approval to institutional review boards by the primary investigators. All patients provided written informed consent before undergoing any study-related procedures
Statistical Method: All efficacy analyses were based primarily on the full analysis set (FAS), which included all patients who received over 1 dose(s) of study treatment. The PFS and ORR were calculated 95% confidence intervals (CIs). Treatment of 39 evaluable patients with the identified phase 2 doses will detect this difference with a power of 80% and alpha=5% (one-sided test). Accounting for a 10% invaluable rate and lead-in patients, a total of 43 patients will be enrolled on the study. Clinical trial information UMIN000014107.
Citation Format: Hajime Abe, Shunji Kamigaki, Yoshifumi Komoike, Nobuki Matsunami, Yoshiaki Nakano, Kenji Tezuka, Junji Tsurutani, Jun Yamamura, Keiichi Yamazaki. A phase 2 study of eribulin in combination with pertuzumab and trastuzumab for advanced or recurrent human epidermal growth factor receptor 2 (HER2)-positive breast cancer (SONG-02) [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr OT3-1-04.