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Targeting human EGFR 2 (HER2) in salivary gland carcinoma
Michael Wotman1, Adel El-Naggar2, Renata Ferrarotto1
1Department of Thoracic-Head & Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
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.
Insights
HER2-positive salivary gland carcinomas (SGC) can be targeted with anti-HER2 therapies in advanced stages. Several treatment options exist for metastatic HER2-positive SGC, with ongoing research for optimal sequencing and novel approaches.
Area of Science:
- Oncology
- Molecular targeted therapy
Background:
- Human epidermal growth factor receptor 2 (HER2) is a therapeutic target in a subset of salivary gland carcinomas (SGC).
- HER2 overexpression and amplification are observed in specific SGC histologies, notably salivary duct carcinoma.
Purpose of the Study:
- To review the evidence and expert opinion on HER2-targeting strategies for HER2-positive SGC.
- To guide treatment selection for patients with advanced, unresectable, recurrent, or metastatic HER2-positive SGC.
Main Methods:
- Review of prospective trials and retrospective series on anti-HER2 therapies in SGC.
- Analysis of expert opinion for treatment recommendations in the palliative setting.
Main Results:
- Anti-HER2 therapies are supported by prospective trials in advanced HER2-positive SGC.
- Treatment options include trastuzumab-based combinations, trastuzumab emtansine (T-DM1), and trastuzumab deruxtecan (T-Dxd).
Conclusions:
- HER2-targeting is recommended for advanced HER2-positive SGC.
- Treatment selection may depend on disease burden and performance status.
- Future research should focus on predictive biomarkers and novel therapeutic combinations.
