Modi S, Park H, Murthy RK, et al. - Given the safety and the activity of trastuzumab deruxtecan [T-DXd, formerly DS-8201a, a new human epidermal growth factor receptor 2 (HER2)-targeted antibody drug conjugate with a topoisomerase I inhibitor payload] was assessed in patients with advanced HER2-expressing/mutated solid tumors in a dose escalation and expansion phase I study, researchers describe outcomes for T-DXd at the recommended doses for expansion (RDE) among patients with HER2-low (immunohistochemistry [IHC] 1+ or IHC 2+/in situ hybridization−) breast cancer. The cases that were eligible for inclusion had advanced/metastatic HER2-low–expressing breast cancer refractory to standard treatments. Until withdrawal of consent, unacceptable toxicity, or progressive disease, the RDE of 5.4 or 6.4 mg/kg T-DXd were given intravenously once every 3 weeks. The validated objective response rate by independent central review was found to be 20/54 and the median duration of response was 10.4 months. Findings revealed promising preliminary antitumor activity of T-DXd in patients with HER2-low breast cancer. Among the toxicities documented, most were GI or hematologic in nature. A crucial identified risk was interstitial lung disease, which requires close monitoring and proactive management.