Response to trastuzumab deruxtecan in a patient with HER2-low metastatic breast cancer previously treated with sacituzumab govitecan

The treatment landscape for metastatic triple negative breast cancer has shifted dramatically in the last few years with the introduction of PARP inhibitors, immunotherapy, and antibody drug conjugates. The two antibody drug conjugates, sacituzumab govitecan (SG) and trastuzumab deruxtecan (T-DXd), were approved by the FDA based on the ASCENT and Destiny-Breast04 trials, respectively. While the antibody targets (Trop-2 and HER2) and compound structures are notably different, both drugs have topoisomerase I inhibitor payloads. Given the payload similarity, the question of if you use one drug will a patient respond to the other one is raised. Here we report the case of a 54-year-old post-menopausal woman with relapsed triple-negative breast cancer in the skin and lymph nodes with a sustained response to T-DXd after progression on SG. We briefly review key differences in the drugs and considerations in therapy sequence. This case shows that T-DXd following SG can potentially have efficacy in patients with HER2-low metastatic breast cancer, though formal studies are needed to quantify the response rate and if the reverse sequence (T-DXd → SG) also has efficacy.