Patients with early HER2-positive/hormone receptor (HR)-positive breast cancer who receive neoadjuvant trastuzumab emtansine (T-DM1) with or without endocrine therapy (ET) for only 12 weeks may achieve a clinically meaningful pathologic complete response (pCR), according to a study published in the Journal of Clinical Oncology.1
Prior studies suggest that T-DM1 may be as effective as current standard therapy — chemotherapy plus anti-HER2 compounds — and has fewer toxic effects.
For this phase 2, prospective trial (ClinicalTrials.gov Identifier: NCT01745965), researchers randomly assigned 375 patients with early HER2-positive/HR-positive breast cancer 1:1:1 to 12 weeks of T-DM1 (3.6mg/kg every 3 weeks for 4 cycles) with or without ET, or to trastuzumab (8mg/kg loading dose, then 6mg/kg every 3 weeks for 4 cycles) with ET.
pCR was confirmed by surgery within 3 weeks of experimental treatment or by histologic confirmation of non-pathologic complete response. Patients also received adjuvant therapy per treatment standards.
pCR, the primary endpoint of the study, was achieved in 41% of patients in the T-DM1 arm, 41.5% in the T-DM1 plus ET arm, and 15.1% in the trastuzumab plus ET arm (P < .001).
The safety profile was favorable across all 3 treatment arms, but a significantly higher prevalence of grade 1 to 2 adverse events (AEs) was observed in the T-DM1 arms. The most frequently reported AEs in T-DM1 were thrombocytopenia, nausea, and elevation of liver enzymes.
The study authors concluded that “T-DM1 may be an efficient and safe alternative for patients who are not suited for systemic chemotherapy in this setting.”
- Harbeck N, Gluz O, Christgen M, et al. De-escalation strategies in human epidermal growth factor receptor 2 (HER2)–positive early breast cancer (BC): final analysis of the west german study group adjuvant dynamic marker-adjusted personalized therapy trial optimizing risk assessment and therapy response prediction in early BC HER2- and hormone receptor–positive phase II randomized trial—efficacy, safety, and predictive markers for 12 weeks of neoadjuvant trastuzumab emtansine with or without endocrine therapy (ET) versus trastuzumab plus ET. J Clin Oncol. 2017 Jul 6. doi: 10.1200/JCO.2016.71.9815 [Epub ahead of print]