Safety of adjuvant trastuzumab emtansine for the treatment of HER2-positive early breast cancer with invasive residual disease

Objective/Purpose: Trastuzumab emtansine (T‐DM1) was approved by the European Medicines Agency (EMA) based on the results of the pivotal trial (PT) “KATHERINE”, for use in the adjuvant treatment of adult patients with HER2‐positive early breast cancer (EBC) who have invasive residual disease, in breast and/or lymph nodes, after neoadjuvant taxane‐based treatment and HER‐2 targeted therapy. T‐DM1 demonstrated a significant benefit achieving an 11% reduction in relapse at 3 years compared to trastuzumab. Our aim is to describe the use of TDM‐1 in patients with HER2‐positive EBC, evaluating its safety profile in clinical practice and comparing it with PT results. Study Design/Methods: Retrospective descriptive study that included patients with HER2‐positive EBC on neoadjuvant T‐DM1 treatment from 01/2021 to 10/ 2022. The following variables were collected from the clinical history and the onco‐haematology prescription programme: age, Eastern Cooperative Oncology Group (ECOG), hormone receptor (HR) status, Ki67, neoadjuvant chemotherapy schedule, T‐DM1 cycles received and end of adjuvant therapy. To assess the safety profile, the occurrence of adverse events (AE), use of filgrastim, dose reductions, delays and treatment interruptions were collected. AE were classified according CTCAE scale v5.0. Results/Key Findings: 14 women with a median age of 55 years (36‐83) were included. ECOG: 0 (78,6%) and 1 (21,4%). HR was positive in 71,4% with a mean Ki67 value of 21%. 50% received neoadjuvant treatment based on Trastuzumab+Docetaxel+Carboplatin (TCH), 14,3% TCH+Pertuzumab, 21,4% Doxorubicin +Cyclophosphamide followed by Paclitaxel with Trastuzumab+Pertuzumab. Of the remaining patients one received Trastuzumab+Pertuzumab and the other Nab‐paclitaxel+Carboplatin+Trastuzumab. Median of T‐DM1 cycles received: 9,5 (1‐14). At the time of analysis 4 patients had completed adjuvant therapy. AE were observed in 85,7% of patients, all grade 1‐2. Most commonly: fatigue 42,9%, increased transaminases 42,9%, anemia 35,7%, platelet count decreased 35,7%, nausea 28,6%, althralgia 28,6%, hypertension 21,4%, headache 14,3%, neutrophil count decreased 14,3%, dyspnea 14,3%, dysphagia 14,3%, dizziness 14,3% and abdominal distension 14,3%. No AE grade ≥ 3 was observed. 28,6% patients received filgrastim, 28,6% had dose reduction, 28,6% experienced delays due to toxicities and no one had treatment discontinuation. In the PT, AE were observed in 98,8% of patients, the most frequent were: fatigue 49,5%, nausea 41,6%, platelet count decreased 28,5%, AST increased 28,4%, headache 28,4%, althralgia 25,9% and ALT increased 23,1%. AE grade ≥ 3 was experienced by 25.7% of patients. 10,4% had dose reduction and 18% treatment discontinuation. Delays in treatment were not recorded in the PT. Conclusion/Recommendations: The AE profile of T‐DM1 in our study was similar to that reported in the PT, however these results should be interpreted with caution considering our limitations of small sample size and short time period; they could be complemented with results obtained in other real‐world cohorts and their comparison with the PT.