The Real-World Clinical Outcomes of Heavily Pretreated HER2+ and HER2-Low Metastatic Breast Cancer Patients Treated with Trastuzumab Deruxtecan at a Single Centre.

backgroundTrastuzumab deruxtecan (TDXd) is an antibody-drug conjugate that has demonstrated impressive activity in randomized controlled clinical trials in the context of patients with HER2-amplified and HER2-low metastatic breast cancer. We aimed to review the activity and adverse event profile of TDXd in heavily pretreated breast cancer patients in real practice.

methodsWe describe a single-center retrospective case series of metastatic breast cancer patients who were treated with TDXd. The outcomes of interest were the overall response rate, overall survival, progression-free survival and grade 4-5 adverse events. Objective responses and PFS were assessed in accordance with RECIST 1.1 criteria.

resultsWe identified 38 patients treated with TDXd. Of these, 15 patients had classically defined HER2-positive (HER2+) breast cancer, 4 of whom had active central nervous system (CNS) metastases. A total of 23 patients had HER2-low breast cancer, 2 of whom had active CNS disease. Of the 33 patients evaluable for response, 21 (63%) patients had a response to treatment, including three (9%) complete responses. Outcomes were similar between patients with a HER2+ and HER2-low status, as well as in patients with or without CNS metastases. No patients experienced grade 4 or 5 toxicities, and four of thirty-eight patients (10.5%) experienced pneumonitis (two patients with grade 3 pneumonitis, one patient with grade 2 and one patient with grade 1), resulting in TDXd discontinuation for three patients (with steroid administration in two patients).

conclusionsTDXd demonstrates impressive activity with manageable adverse event profiles in this heavily pretreated population that includes patients with active CNS metastases.