Trastuzumab emtansine (T-DM1) versus trastuzumab in Chinese patients with residual invasive disease after neoadjuvant chemotherapy and HER2-targeted therapy for HER2-positive breast cancer in the phase 3 KATHERINE study

• Published in: Breast cancer research and treatment 2021-06, Vol.187 (3), p.759-768
• Main Authors: Huang, Chiun-Sheng, Yang, Youngsen, Kwong, Ava, Chen, Shin-Cheh, Tseng, Ling-Ming, Liu, Mei-Ching, Shen, Kunwei, Wang, Shusen, Ng, Ting-Ying, Feng, Yi, Sun, Guofang, Yan, Iris Renfei, Shao, Zhimin
• Format: Article
• Language: English
• Subjects: Adjuvant treatment; Ado-Trastuzumab Emtansine; Adverse events; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Breast cancer; Breast Neoplasms - drug therapy; Cancer; Cancer research; Care and treatment; Chemotherapy; China; Clinical Trial; Comparative analysis; Complications and side effects; ErbB-2 protein; Female; Hemorrhage; Humans; Invasiveness; Maytansine - adverse effects; Medicine; Medicine & Public Health; Metastases; Metastasis; Monoclonal antibodies; Neoadjuvant Therapy; Oncology; Oncology, Experimental; Patients; Receptor, ErbB-2 - genetics; Surgery; Targeted cancer therapy; Thrombocytopenia; Trastuzumab; Trastuzumab - adverse effects
• ISSN: 0167-6806; 1573-7217
• DOI: 10.1007/s10549-021-06166-y

Purpose In the KATHERINE study (NCT01772472), patients with HER2-positive early breast cancer (EBC) and residual invasive disease after neoadjuvant chemotherapy plus HER2-targeted therapy who were treated with adjuvant trastuzumab emtansine (T-DM1) had a 50% reduction in the risk of an invasive disease-free survival (IDFS) event compared to patients treated with adjuvant trastuzumab. In metastatic disease, T-DM1 has resulted in higher rates of thrombocytopenia in Asian versus non-Asian patients. Here, we report safety and efficacy in Chinese patients from KATHERINE. Methods Patients with HER2-positive EBC and residual invasive disease after taxane- and trastuzumab-containing neoadjuvant chemotherapy followed by surgery were randomized 1:1 to 14 cycles of adjuvant T-DM1 or trastuzumab. The primary endpoint was time to an IDFS event. Results Among Chinese patients (T-DM1 n  = 51, trastuzumab n  = 50), T-DM1 treatment resulted in a 43% reduction in risk of an IDFS event compared to trastuzumab (HR = 0.57; 95% CI 0.25–1.31), with similar results for secondary endpoints. As in the global population, Chinese patients receiving T-DM1 versus trastuzumab had more grade ≥ 3 adverse events (AEs; 39.2% versus 4.1%) and AEs leading to treatment discontinuation (27.5% versus 0%). The most common grade ≥ 3 AE with T-DM1 was thrombocytopenia (21.6%), a frequency higher than the frequency in the global population (5.7%). Grade ≥ 3 hemorrhage was reported in 1 patient (T-DM1 arm). Conclusions In the KATHERINE study, T-DM1 demonstrated increased efficacy compared to trastuzumab in Chinese patients. Consistent with previous data in Asian patients, T-DM1 was associated with more grade ≥ 3 AEs, and AEs leading to discontinuation, which was driven by an increase in thrombocytopenia.