Targeting human EGFR 2 (HER2) in salivary gland carcinoma.

INTRODUCTION: 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.

AREAS COVERED: 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).

EXPERT OPINION: 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.