Comparison of the efficacy of trastuzumab emtansine between patients with metastatic human epidermal growth factor receptor 2-positive breast cancers previously treated with combination trastuzumab and pertuzumab and with trastuzumab only in Japanese population

Shoko Noda-Narita,Chikako Shimizu,Kazuki Sudo,Kan Yonemori,Yasuhiro Fujiwara,Emi Noguchi,Kenji Tamura,Akihiko Shimomura,Hitomi Sumiyoshi-Okuma,Tatsunori Shimoi,Asuka Kawachi

doi:10.1007/s12282-019-00949-4

Abstract

BackgroundTrastuzumab emtansine (T-DM1) has been approved since 2013 for patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC) who had received trastuzumab (Tmab) and taxane. However, no clinical trial has evaluated the efficacy of T-DM1 in those who have previously received pertuzumab (Pmab). This study aimed to compare the efficacy of T-DM1 between patients who had received Tmab and Pmab and those who had received Tmab only in Japanese population.MethodsWe identified all patients with HER2-positive MBC who received T-DM1 between April 1, 2014 and February 28, 2017 in our institution. The patients were divided into the Tmab group (i.e., those who received only Tmab before T-DM1 treatment) and the Tmab/Pmab group (i.e., those who received Tmab and Pmab before T-DM1 treatment), and progression-free survival (PFS) and best response were compared between the two groups.ResultsA total of 42 patients were enrolled for outcome analysis. The median follow-up period was 4.8 months, and the median number of prior chemotherapy regimens for metastatic disease before T-DM1 was 1 (range 1–2) in the Tmab/Pmab group and 2 (range 0–6) in the Tmab group. The median PFS was 2.8 months in the Tmab/Pmab group (95% confidence interval [CI] 1.7–4.8 months) and 7.8 months in the Tmab group (95% CI 5.5–15.9 months) (p = 0.0030). The best response was lower in the Tmab/Pmab group (11.1% vs. 25.0%).ConclusionsPatients with HER2-positive MBC who received Tmab and Pmab treatment before T-DM1 have fewer benefits from T-DM1.

Highlights

The introduction of trastuzumab (Tmab), a monoclonal antibody targeting human epidermal growth factor receptor 2 (HER2), has substantially improved the prognosis of HER2-positive breast cancer
T-DM1 treatment was discontinued in 40 patients due to Progressive disease (PD) (n = 38, 95%), diagnosis of another tumor, and because of treatment-related anorexia (n = 1, 2.5%). This is the first report to demonstrate the efficacy of T-DM1 in patients who had previously received Tmab and Pmab compared with patients who had received only Tmab in Japanese population
Our study showed the shorter median progressionfree survival (PFS) of 2.8 months and lower Tumor response rate (TRR) of 11.1% in the Tmab/Pmab group compared to the Tmab group

Summary

Introduction

The introduction of trastuzumab (Tmab), a monoclonal antibody targeting human epidermal growth factor receptor 2 (HER2), has substantially improved the prognosis of HER2-positive breast cancer. T-DM1 is an antibody-drug conjugate consisting of Tmab and the cytotoxic agent emtansine It showed substantial benefits in progression-free survival (PFS) and overall survival (OS) compared with capecitabine and Lapa in patients with HER2-positive MBC who had previously received Tmab and taxane in the phase III EMILIA trial (median PFS, 9.6 months vs 6.4 months; hazard ratio [HR] 0.65) [1, 2]. It was approved as second-line therapy for patients with HER2-positive MBC who previously received Tmab and a taxane by the United States Food and Drug Administration in February 2013 and in September 2013 in Japan. Conclusions Patients with HER2-positive MBC who received Tmab and Pmab treatment before T-DM1 have fewer benefits from T-DM1

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