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Human epidermal growth factor receptor 2 (HER2) protein overexpression, gene amplification, and activating mutations have been identified in a subset of salivary gland carcinoma (SGC) histologies (HER2-positive), especially in salivary duct carcinoma, and represent an important therapeutic target. The evidence for targeting HER2 in the adjuvant setting is limited to small retrospective series. Conversely, there are prospective trials supporting the use of anti-HER2 therapy in patients with unresectable, recurrent, or metastatic HER2-positive SGC, including trastuzumab plus docetaxel, trastuzumab plus pertuzumab, trastuzumab-pkrb plus nanoxel, trastuzumab emtansine (T-DM1), and trastuzumab deruxtecan (T-Dxd). HER2-targeting should be considered for patients with advanced HER2-positive SGC. There are no data to guide the selection of one anti-HER2 agent over another in the palliative setting. Trastuzumab plus docetaxel can be considered for patients with a high disease burden, while trastuzumab plus pertuzumab is a good option for patients with low disease burden or borderline performance status. T-DM1 or T-Dxd can be considered upon disease progression on trastuzumab-combination therapies, although these antibody-drug conjugates can also be used upfront. Future research should investigate predictive biomarkers, the combination of HER2 and androgen blockade, and the application of novel therapies from breast cancer.

Targeting human EGFR 2 (HER2) in salivary gland carcinoma