Safety Evaluation of Trastuzumab Emtansine in Japanese Patients with HER2-Positive Advanced Breast Cancer

Abstract

Abstract. Background/Aim: Tolerability and safety of trastuzumab emtansine (T-DM1) was investigated inThe human epidermal growth factor receptor 2 (HER2) has been shown to play an important role in the development and progression of certain types of breast cancer. HER2 is overexpressed in ~20% of patients with breast cancer and is associated with a more aggressive tumor growth and poor clinical outcome (1-3). Since trastuzumab, an anti-HER2 humanized monoclonal antibody, demonstrated the significant survival benefit in patients with HER2-positive metastatic breast cancer (4), combination of anti-HER2 therapy with standard chemotherapy has been used as an effective therapeutic approach for patients with HER2-positive advanced breast cancer. In addition, dual blockade of HER2 with combination of pertuzumab and trastuzumab plus chemotherapy showed significant improvement in overall survival compared to trastuzumab plus chemotherapy (5). To date, several novel anti-HER2 therapeutic agents, including trastuzumab, lapatinib, pertuzumab, and trastuzumab emtansine, have been developed.Trastuzumab emtansine, known as T-DM1, is an antibody drug conjugate incorporating trastuzumab with microtubuleinhibitory agent DM1 (derivative of maytansine); the anti-HER2 antibody and cytotoxic agent are conjugated via a 493 This article is freely accessible online.

Research progress of antibody-drug conjugates therapy for HER2-low expressing gastric cancer

“…In recent years, with the research and development of tumor molecular biology, it has been found that the positive expression of the HER2 receptor is associated with the poor prognosis of GC [3] . It is considered a new biomarker diagnostic factor and the preferred target for cancer therapy, bringing tumor treatment into a new era [13] , [14] , [15] , [16] . Inhibiting HER2 activity with monoclonal antibodies, ADC, or small molecular kinase inhibitors are common methods for the treatment of HER2-positive GC.…”

Low Eosinophil Percentages as a New Predictive Marker for Infusion Reactions Due to Trastuzumab

“…Additionally, the incidence of IRs in Japanese patients who had received the trastuzumab emtansine was 1.7% (4/232) and much lower in this study (6). The difference could be explained by the fact that patients with previous treatment of trastuzumab and without severe IRs due to trastuzumab were included in the previous study.…”

Treatment-related adverse events associated with HER2-Targeted antibody-drug conjugates in clinical trials: a systematic review and meta-analysis

“…Of the 37 trials included in the systematic review, 13 were randomized controlled trials (RCTs) 11 , 12 , 14 , 15 , 18 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 and 24 were single-arm clinical trials. 13 , 16 , 17 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 The HER2-targeted ADCs used in eligible studies included T-DM1 (n = 25) and T-DXd (n = 14). The studies involved the treatment of breast cancer (n = 28), lung cancer (n = 4), gastric cancer (n = 4), colorectal cancer (n = 1), and mixed cancer types (n = 2).…”