Trastuzumab for the Treatment of Salivary Duct Carcinoma

Abstract

Objectives. Salivary duct carcinoma (SDC) is a rare and aggressive malignancy with high mortality and poor response to treatment. A significant fraction of SDCs are HER2 positive. This retrospective review examines HER2 testing in SDC and the outcome of trastuzumab-based therapy in adjuvant and palliative settings. Methods. A total of 13 patients with SDC and HER2/neu expression by immunohistochemistry of 1-3ϩ were treated with trastuzumab in adjuvant (n ϭ 8) or palliative (n ϭ 5) setting. Adjuvant therapy consisted of concurrent radiation and chemotherapy with weekly paclitaxel, carboplatin, and trastuzumab (TCH) for 6 weeks followed by TCH for 12 weeks and trastuzumab alone for 1 year. Palliative treatment for metastatic disease consisted of TCH every 3 weeks for 6 cycles followed by trastuzumab for variable time periods with or without second-line chemotherapy for progression. All patients had fluorescence in situ hybridization testing for HER2/ neu gene amplification. Results. The median duration of follow-up was 27 months (range: 8 -48 months). In all, 62% of adjuvant patients (5/8) had no evidence of disease more than 2 years from completion of therapy. All patients with metastatic disease (5/5 patients) responded to treatment with TCH. One patient achieved a complete response and remains with no evidence of disease 52 months after initiation of TCH. The median duration of response was 18 months (range: 8 -52 months). Conclusion. HER2/neu positivity and treatment with trastuzumab correlated well with long-term survival and response in our patients. Based on this data, we propose that HER2/neu status be examined routinely in all patients with SDCs and the treatment be directed accordingly. The Oncologist 2013;18: 294 -300 Implications for Practice: Salivary duct carcinoma (SDC) is an extremely rare and aggressive type of salivary gland cancer with high morbidity and mortality. Current treatment options of surgery with or without radiation therapy provide limited benefit. Conventional chemotherapeutic agents have been utilized in the palliative setting with modest results. Randomized prospective clinical trials are difficult due to the rarity of the disease. Newer treatment strategies are needed to improve outcomes. At DanaFarber Cancer Institute, we treated HER2 positive SDCs with trastuzumab-based therapy with excellent results. Patients with HER2 positive SDC received a combination of paclitaxel, carboplatin and trastuzumab (TCH) in the palliative or adjuvant setting. Although the results below are from a small cohort of patients, treatment with trastuzumab correlated well with long-term survival and response to therapy. The unique application of this treatment in the adjuvant and palliative setting is practice changing and could have direct clinical implications.

Somatic mutations in salivary duct carcinoma and potential therapeutic targets

“…There are several reports of patients treated with androgen deprivation therapy, Trastuzumab and Venmurafinib for metastatic SDCa with partial to complete response [30][31][32][33][34][35]. However, these modalities have not been accepted as mainstream treatments for SDCa.…”

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

“…Recent studies of novel treatment strategies for SDC investigated the systemic use of molecularly targeted therapies (14)(15)(16)(35)(36)(37). Trastuzumab, which targets HER2, effectively prevents the recurrence of metastatic HER2-positive breast cancer.…”

“…SDC histologically resembles intraductal and infiltrating mammary duct carcinoma, and previous studies reported the therapeutic efficacy of adjuvant or palliative trastuzumab, carboplatin and paclitaxel for SDC, which frequently overexpresses HER2 (14-16,35-37). Limaye et al described 8 patients with HER2-positive SDC who were treated with concurrent radiation and chemotherapy consisting of weekly paclitaxel, carboplatin and trastuzumab after surgical resection, followed by adjuvant trastuzumab monotherapy (16). Of the patients who received adjuvant therapy, 38% experienced recurrence, but all patients with metastatic disease responded to treatment with trastuzumab.…”

“…Of the patients who received adjuvant therapy, 38% experienced recurrence, but all patients with metastatic disease responded to treatment with trastuzumab. One patient achieved a CR and currently has no evidence of disease (16). Furthermore, trastuzumab was found to be superior to conventional chemotherapy for the treatment of distant metastasis, and palliative and adjuvant trastuzumab-based therapy should be considered for all patients with HER2-positive SDC (14-16,35-37).…”

“…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.…”