Background and importance Trastuzumab-emtansine (T-DM1) is a treatment approved by the European Medicines Agency (EMA) in 2020 as a single agent for the adjuvant treatment of adult patients with HER2-positive early breast cancer (EBC) who have residual invasive disease, in the breast and/or lymph nodes, after neoadjuvant taxane-based and HER2-targeted therapy, in which it demostrated a significant improvement in invasive disease-free survival compared with trastuzumab.¹

Aim and objectives Aim: to describe our experience with T-DM1 adjuvant for EBC treatment in real-world conditions (RWC). We analysed the T-DM1 safety profile and compared it with a pivotal trial (PT).¹

Material and methods Retrospective study in a tertiary hospital. 100% patients with EBC treated with adjuvant T-DM1 between 2019 and 2021.

Demographic data, basal Eastern Cooperative Oncology Group (ECOG), neoadjuvant therapy schedule, T-DM1 cycles received, adverse events (AEs), pegfilgastrim use, intentional dose delays, treatment interruptions and dose reductions were collected.

Results 29 patients received T-DM1. 100% women, average age 52 (range 27–75) years. 2/29 basal ECOG ≥1.

20/29 received neoadjuvant treatment based on doxorubicin (lyposomal or conventional) and cyclophosphamide followed by taxanes (19/20 paclitaxel, 1/20 docetaxel) with trastuzumab and pertuzumab. 24/29 presented toxicities to neoadjuvant treatment (15/29 thrombocytopenia).

T-DM1 starting dose: 3.6 mg/kg/21 days in 28/29 patients. In 1/29, 3 mg/kg due to persistent thrombocytopenia. 10/29 receiving therapy at the time of the study. 8/19 received <14 cycles, 5/8 discontinued due to toxicities.

19/29 experienced ≥1 AE. Grade ≥3 thrombocytopenia was the most common (12/29), followed by increase in liver enzymes (ILE) (6/29), grade ≥2 neuropathy and grade ≥2 asthenia (5/29).

2/29 received pegfilgrastim.

3/29 patients had dose reduction (2/29 one, 1/29 two dose-level reductions). 7/29 experienced dose delays due to toxicities.

Comparison RWC vs PT: any grade AE 65.5% vs 98.8%; grade ≥3 thrombocytopenia 41.4% vs 5.7%; grade ≥2 neuropathy 34.5% vs 1.5%; ILE 20.7% vs 5.6%; discontinuation due to toxicities 17.2% vs 18.0%; dose reductions 10.3% vs 10.4%. Dose delays and reduced initial dose were not considered in the PT.

Conclusion and relevance Safety profile of T-DM1 in RWC is consistent with the PT results. Overall AEs in RCW were lower than in the PT. Grade ≥2 AEs were higher in RWC but not related to increased discontinuations or dose reductions. Our results should be interpreted with caution due to the sample size.

References and/or acknowledgements 1. von Minckwitz G, et al. Trastuzumab emtansine for residual invasive HER2-positive breast cancer. N Engl J Med 2019;380(7):617–628.

Conflict of interest No conflict of interest