Metastatic Parotid Gland Carcinoma With ERBB2 Amplification With Complete Response to Fam‐Trastuzumab Deruxtecan

Abstract

HER2 mutations have been shown to be targetable in select cases of salivary gland cancers with overexpression or amplification of the HER2 oncogene. Fam-trastuzumab deruxtecan, a novel antibody–drug conjugate that combines trastuzumab with a topoisomerase I inhibitor, has recently demonstrated efficacy as a third-line agent in HER2-overexpressing breast cancer after trastuzumab failure. These promising results in breast cancer suggest a potential paradigm for use in other tumors with known HER2 alterations, including salivary gland cancer. This report describes a 67-year-old man with HER2-positive metastatic parotid gland carcinoma who experienced disease progression after parotidectomy with adjuvant cisplatin-based chemoradiation, neratinib, and ado-trastuzumab emtansine. After disease progression on the latter HER2-directed therapy, his malignancy demonstrated complete response to fam-trastuzumab deruxtecan, which has been sustained for the past 7 months. Fam-trastuzumab deruxtecan appears to be a well-tolerated therapeutic option in patients with HER2-positive salivary gland carcinoma, with activity demonstrated after progression on ado-trastuzumab emtansine and HER2-directed kinase inhibition. Further studies should be conducted to explore the use of this agent in HER2-positive salivary gland cancers.

Metastatic Salivary Duct Carcinoma with ERBB2 Amplification and Sequential Response to Ado-Trastuzumab Emtansine and Neratinib: A Case Report

“…Prospective registries might evaluate how far relatively innovative drugs can also overcome potential HER2 resistances and improve the patient outcome [14][15][16][17]. Indicatively, one recent case report documented a complete response to fam-trastuzumab deruxtecan after disease progression on neratinib and T-DM1 [8]. We also observed the importance and relevance of personalized and adaptive treatments,…”

“…With respect to demographics and tumor biology, an increasing number of reports on targeted treatments, in particular AR blockade and HER-2-targeted drugs such as T-DM1 and neratinib, can be found in the literature [4]. Disease control with both anti-hormonal strategies and growth factor receptor blockade demonstrates disease control comparable to conservative chemotherapeutic regimens, albeit with much lower collateral side effects [4][5][6][7][8]. However, as to our knowledge, a patient with sequential bicalutamide, enzalutamide, T-DM1, and neratinib therapy resulting in disease control of almost 3 years has not been reported previously.…”

“…Prospective registries might evaluate how far relatively innovative drugs can also overcome potential HER2 resistances and improve the patient outcome [14‒17]. Indicatively, one recent case report documented a complete response to fam-trastuzumab deruxtecan after disease progression on neratinib and T-DM1 [8]. We also observed the importance and relevance of personalized and adaptive treatments, especially in patients with rare tumors, like SDC, according to the tumor’s biology and stress the significance of exploring treatment options and reimbursement streams progressively based also on real-world well-being and performance as is reported by the patient (electronically captured patient-reported outcomes) [12].…”

“…Next-generation sequencing (NGS, FoundationOne ® CDx) had also been performed, which revealed that the AKT1 gene and the CDK6 gene were amplified. However, due to the limited availability of reliable treatments for these two genes, it was decided to target primarily the ERBB2 pathway as two recent studies had revealed an overall high response rate in patients with HER-2-amplified salivary gland carcinomas treated with ado-trastuzumab emtansine (T-DM1), an antibody-drug conjugate consisting of the monoclonal antibody trastuzumab linked to the microtubule poison DM1 [ 8 ]. Therefore, the patient initiated treatment with T-DM1, in August 2020.…”

“…Due to an obvious progression in July 2021, we then initiated monotherapy with neratinib (240 mg/day), an irreversible tyrosine kinase inhibitor [ 9 ]. Clinical data on the efficacy of neratinib as a treatment of SDCs are described with clinical benefits of several months [ 8 ] and in patients suffering from SDC with brain metastases [ 10 ]. Although up to 85% of patients may suffer from diarrhea during treatment with neratinib, this compound was well tolerated by our patient, and he achieved good stable disease during this course of treatment [ 9 ].…”