Human epidermal receptor 2–amplified salivary duct carcinoma: Regression with dual human epidermal receptor 2 inhibition and anti–vascular endothelial growth factor combination treatment

Abstract

Background Salivary ductal carcinoma is a rare cancer with poor prognosis and limited treatment options. HER2-directed treatment has been attempted in HER2-amplified or overexpressed salivary gland malignancies with limited success. Methods We report resolution of measurable disease and minimal residual disease in a patient with salivary duct cancer treated with trastuzumab, lapatinib, and bevacizumab, with treatment ongoing for more than two years. Results This treatment has been tolerated well except for grade 2 diarrhea and mucositis, which required a dose reduction of lapatinib to 1000 mg daily. The response observed was achieved in spite of receiving extensive prior therapy, including trastuzumab and/or chemotherapy for 20 months on which his tumors progressed. Conclusions The combination of trastuzumab, lapatinib, and bevacizumab may warrant investigation as a non-cytotoxic alternative for treatment of HER2-amplified or overexpressed salivary duct carcinoma and other HER2-amplified or overexpressed salivary gland tumors, particularly those not responsive to trastuzumab monotherapy.

Profiling of 149 Salivary Duct Carcinomas, Carcinoma Ex Pleomorphic Adenomas, and Adenocarcinomas, Not Otherwise Specified Reveals Actionable Genomic Alterations

“…Additionally, we also identified a high number of ERBB2 GAs in ductal ca ex PA. New to this study was the identification of activating ERBB2 mutations in adenocarcinoma, NOS, SDC, and ductal ca ex PA. HER2 targeted therapies, such as trastuzumab, have previously demonstrated efficacy in ERBB2 amplified salivary gland cancers, and contributed a partial response in our series (41,42). Select GAs in genes with precision drugs currently commercially available included ROS1, MET, and BRAF, though BRAF GAs were seen less frequently that previously reported (11).…”

A phase I trial of combination trastuzumab, lapatinib, and bevacizumab in patients with advanced cancer

“…A HER2-amplified salivary duct cancer patient in this study achieved resolution of measurable disease and minimal residual nonmeasurable disease for 27+ months. This patient was heavily pretreated with trastuzumab used in combination with radiation therapy or cytotoxic chemotherapy after which his tumor progressed suggesting that the combination overcame prior resistance to trastuzumab [46]. A HER2-mutant non-small cell lung cancer patient also achieved prolonged stable disease on this study combination, after progressing on prior systemic chemotherapy [41].…”

Salivary duct carcinoma treated with cetuximab-based targeted therapy: A case report

“…This type of cancer resembles intraductal and infiltrating mammary duct carcinomas with a variety of histoarchitectural and cytological patterns. Approximately 61-100% of the cases are reported to be human epidermal growth factor receptor 2 (HER2)-positive (13,14), and a correlation has been identified between HER2 expression and prognosis (13)(14)(15)(16). Additionally, 50-70% of SDCs express epidermal growth factor receptor (EGFR; HER1) (17)(18)(19), and anti-EGFR-targeted therapies, such as cetuximab, are expected to be useful as novel SDC treatments.…”