Efficacy and toxicity of post-neoadjuvant trastuzumab emtansine in HER2-positive breast cancer patients treated at Institut Curie Hospitals.

In human epidermal growth factor receptor 2 (HER2) positive early breast cancer (EBC) patients, with residual invasive disease after neoadjuvant chemotherapy (NACT) plus HER2-targeted therapy, the KATHERINE trial demonstrated a 50% reduction in risk of recurrence or death with adjuvant trastuzumab emtansine (T-DM1) versus trastuzumab. A retrospective bicentric cohort study was set to assess the real-world efficacy and safety of T-DM1 as adjuvant therapy in HER2-positve EBC patients treated at Institut Curie Hospitals. N = 102 patients consecutively treated from September 2019 to January 2021 were included. All patients had previously received neoadjuvant trastuzumab (plus pertuzumab in one patient) and chemotherapy, N = 95 (93%) with anthracyclines. Post-neoadjuvant residual cancer burden was RCB I, II and III in N = 28 (27%), 62 (61%) and 11 (11%) patients, respectively, while N = 70 (69%) had an estrogen receptor-positive disease. After a median follow-up of 44 months (range 4.5-54), N = 7 (7%) patients experienced distant tumor recurrence, including central nervous system (CNS) metastases in N = 5 patients, leading to death in N = 2 patients, while no local recurrence was reported. The 4-years disease-free survival (DFS) rate was 92.5% (95%CI=[87;98]), lymph node involvement at diagnosis (cN+) being the only factor associated with a higher risk of relapse (p = 0.025, no event in the node negative group in our population). Dose reductions of T-DM1 were required in N = 34 patients (33%) after a median of 5 cycles, mainly because of peripheral neuropathy (N = 14), increased alanine and/or aspartate aminotransferase level (N = 9), and thrombopenia (N = 6). Adverse event leading to drug discontinuation occurred in N = 23 patients (23%), after a median of 9 cycles, mostly peripheral neuropathy (N = 10) and thrombopenia (N = 9). Grade 3-4 toxicity affected N = 9 patients (9%), with no related death to T-DM1. With a low relapse rate and although more dose reductions and treatment discontinuation were observed in our cohort, our results are consistent with those of the KATHERINE trial. CNS as the most frequent site of relapse points to a potential role for drugs with higher activity against CNS metastases.