Trastuzumab deruxtecan (HER2 ADC) drives 67% RECIST responses in HER2-low/HER2-mutant salivary/lacrimal cancers

Trastuzumab deruxtecan (T-DXd; DS-8201), a HER2-directed antibody–drug conjugate delivering a topoisomerase I inhibitor payload, was given to patients with recurrent/metastatic secretory gland cancers of the head and neck with HER2-low (IHC 1+ or IHC 2+/ISH−) or HER2-activating mutations in an MD Anderson case series (any line; largely off-label). In 9 patients (SGC n=8; LGC n=1; HER2-low n=7; HER2-mutant n=2), 6 were RECIST-evaluable and 4/6 achieved a partial response (66.7%), including 1 complete response in target lesions; the 3 non–RECIST-evaluable patients had clinician-documented clinical and/or radiographic improvement, and median time on treatment for the full cohort was 8.9 months. While cross-trial comparisons are shaky, this activity looks at least in the ballpark of HER2-positive SGC benchmarks (e.g., T-DXd in HER2-expressing SGC ORR ~59% [10/17] with median PFS 20.5 months in a pooled phase I analysis; and trastuzumab+pertuzumab in HER2-amplified/overexpressing SGC ORR 60% with median PFS 8.6 months), but here the key novelty is responses in HER2-low/HER2-mutant disease where “standard” systemic options are typically limited and less targetable.