Evaluating post-trastuzumab deruxtecan treatment strategies in HER2-positive metastatic breast cancer

Trastuzumab deruxtecan (T-DXd) is an antibody-drug conjugate (ADC) approved for the treatment of HER2-positive metastatic breast cancer (mBC). Despite its efficacy, eventual resistance and disease progression are common. A retrospective study at Memorial Sloan Kettering Cancer Center (New York, NY) analyzed post-T-DXd treatment strategies. The study included 81 patients, who received 199 lines of therapy collectively. Post-T-DXd therapies included other ADCs, chemotherapy, HER2-targeted antibodies, hormone-based therapy, tyrosine kinase inhibitors, and clinical trials. The median overall survival after stopping T-DXd treatment was 19 months, with a median progression-free survival of 3.7 months per subsequent treatment line. No single therapeutic approach was clearly superior, although subsets of patients appeared to benefit from hormone therapy or TKIs. Patients who discontinued T-DXd due to toxicity, rather than disease progression, had significantly better outcomes on subsequent therapy lines. The authors conclude that patients emerge from T-DXd treatment with highly refractory disease, highlighting the urgent need for optimized treatment strategies and novel therapeutic options for this patient population.