Trastuzumab Deruxtecan in HER2-Low or HER2-Mutant Recurrent/Metastatic Secretory Gland Cancers of the Head and Neck: A Case Series

Trastuzumab deruxtecan (T-DXd) has shown efficacy in HER2-positive (immunohistochemistry [IHC] 3+ or IHC 2+/in situ hybridization [ISH]+) recurrent/metastatic (R/M) secretory gland cancers of the head and neck. However, there are minimal published data regarding the use of T-DXd in HER2-low (IHC 1+ or IHC 2+/ISH−) or HER2 -mutant tumors. This case series aimed to describe the clinical characteristics and outcomes of patients with HER2-low or HER2 -mutant R/M salivary gland cancer (SGC) or lacrimal gland cancer (LGC) who received T-DXd in any line of therapy. Patients included in this series had a confirmed diagnosis of SGC or LGC, were evaluated at the MD Anderson Head and Neck Center, and received at least one dose of T-DXd. HER2 status was evaluated according to ASCO/CAP guidelines for breast cancer as recommended by NCCN. HER2 -activating mutations were identified with tissue-based next-generation sequencing. Best overall response to T-DXd per RECIST v1.1 was evaluated for patients with adequate imaging and measurable disease. The final cohort comprised 9 patients (SGC, n=8; LGC, n=1), including 7 with HER2-low and 2 with HER2 -mutant tumors. T-DXd was given off-label in 7 patients; 2 received T-DXd on a clinical trial. Among 6 patients who were eligible for RECIST, 4 (66.7%) had a partial response, including 1 complete response in target lesions. The 3 patients who were not eligible for RECIST had oncologist-documented clinical and/or radiographic improvement. The median time on T-DXd among all patients was 8.9 months. T-DXd demonstrated promising and durable antitumor activity. This antibody–drug conjugate should be considered a viable therapeutic option for HER2-low and HER2 -mutant R/M SGC/LGC, with potential use in the frontline setting when preferred systemic therapies are unavailable.