Breast Cancer Research and Treatment | 2021
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
Abstract
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. 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. Among Chinese patients (T-DM1 n\u2009=\u200951, trastuzumab n\u2009=\u200950), T-DM1 treatment resulted in a 43% reduction in risk of an IDFS event compared to trastuzumab (HR\u2009=\u20090.57; 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\u2009≥\u20093 adverse events (AEs; 39.2% versus 4.1%) and AEs leading to treatment discontinuation (27.5% versus 0%). The most common grade\u2009≥\u20093 AE with T-DM1 was thrombocytopenia (21.6%), a frequency higher than the frequency in the global population (5.7%). Grade\u2009≥\u20093 hemorrhage was reported in 1 patient (T-DM1 arm). 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\u2009≥\u20093 AEs, and AEs leading to discontinuation, which was driven by an increase in thrombocytopenia.