Salivary gland cancers are a heterogeneous collection of malignancies defined primarily by different histologies, which include adenoid cystic carcinoma (ACC), mucoepidermoid carcinoma, and salivary duct carcinoma (SDC). In particular, SDC is a neoplasm known for both its poor prognosis and its rarity. Because of these characteristics, data are currently insufficient to confidently recommend a standard of care for these tumors.
Recently, clinical oncologists have had increasing access to tumor genomic profiling, which allows for identification of mutations, gene fusions, and copy number variants that may predict response to specific targeted therapies. This approach has been of particular interest in so-called difficult-to-treat cancers, which include rare malignancies such as SDC, that have a very limited evidence base to guide treatment decisions. This report presents a patient with a widely metastatic SDC harboring a BRAF p.V600E mutation that was treated with a precision oncology approach developed in conjunction with the University of Alabama at Birmingham (UAB) Molecular Tumor Board (MTB).1 To our knowledge, this is the first reported use of combined BRAF and MEK inhibition for the treatment of metastatic BRAF-mutated SDC in the frontline setting.
The authors have disclosed that they have no financial interests, arrangements, affiliations, or commercial interests with the manufacturers of any products discussed in this article or their competitors.
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HaradaSArendRDaiQ. Implementation and utilization of the molecular tumor board to guide precision medicine. Oncotarget2017;8:57845–57854.
AlfieriSGranataRBergaminiC. Systemic therapy in metastatic salivary gland carcinomas: a pathology-driven paradigm?Oral Oncol2017;66:58–63.
LaurieSAHoALFuryMG. Systemic therapy in the management of metastatic or locally recurrent adenoid cystic carcinoma of the salivary glands: a systematic review. Lancet Oncol2011;12:815–824.
PfefferMRTalmiYCataneR. A phase II study of imatinib for advanced adenoid cystic carcinoma of head and neck salivary glands. Oral Oncol2007;43:33–36.
WongSJKarrisonTHayesDN. Phase II trial of dasatinib for recurrent or metastatic c-KIT expressing adenoid cystic carcinoma and for nonadenoid cystic malignant salivary tumors. Ann Oncol2016;27:318–323.
NakanoKSatoYSasakiT. Combination chemotherapy of carboplatin and paclitaxel for advanced/metastatic salivary gland carcinoma patients: differences in responses by different pathological diagnoses. Acta Otolaryngol2016;136:948–951.
OsbornVGiviBLeeA. Characterization, treatment and outcomes of salivary ductal carcinoma using the National Cancer Database. Oral Oncol2017;71:41–46.
JaspersHCVerbistBMSchoffelenR. Androgen receptor-positive salivary duct carcinoma: a disease entity with promising new treatment options. J Clin Oncol2011;29:e473–476.
DalinMGDesrichardAKatabiN. Comprehensive molecular characterization of salivary duct carcinoma reveals actionable targets and similarity to apocrine breast cancer. Clin Cancer Res2016;22:4623–4633.
TakahashiHMasubuchiTFushimiC. Trastuzumab and docetaxel for HER2-positive unresectable salivary gland carcinoma: updated results of a phase II trial [abstract]. Presented at the 2016 AHNS Annual Meeting; July16–202016; Seattle, Washington.
van BoxtelWBoonEWeijsWL. Combination of docetaxel, trastuzumab and pertuzumab or treatment with trastuzumab-emtansine for metastatic salivary duct carcinoma. Oral Oncol2017;72:198–200.
FanCYWangJBarnesEL. Expression of androgen receptor and prostatic specific markers in salivary duct carcinoma: an immunohistochemical analysis of 13 cases and review of the literature. Am J Surg Pathol2000;24:579–586.
YamamotoNMinamiSFujiiM. Clinicopathologic study of salivary duct carcinoma and the efficacy of androgen deprivation therapy. Am J Otolaryngol2014;35:731–735.
PlanchardDBesseBGroenHJ. Dabrafenib plus trametinib in patients with previously treated BRAF(V600E)-mutant metastatic non-small cell lung cancer: an open-label, multicentre phase 2 trial. Lancet Oncol2016;17:984–993.
PettirossiVSantiAImperiE. BRAF inhibitors reverse the unique molecular signature and phenotype of hairy cell leukemia and exert potent antileukemic activity. Blood2015;125:1207–1216.
SubbiahVKreitmanRJWainbergZA. Dabrafenib and trametinib treatment in patients with locally advanced or metastatic BRAF V600–mutant anaplastic thyroid cancer. J Clin Oncol2018;36:7–13.
LongGVHauschildASantinamiM. Adjuvant dabrafenib plus trametinib in stage III BRAF-mutated melanoma. N Engl J Med2017;377:1813–1823.
PlanchardDSmitEFGroenHJ. Dabrafenib plus trametinib in patients with previously untreated BRAFV600E-mutant metastatic non-small-cell lung cancer: an open-label, phase 2 trial. Lancet Oncol2017;18:1307–1316.
KlempnerSJGershenhornBTranP. BRAFV600E mutations in high-grade colorectal neuroendocrine tumors may predict responsiveness to BRAF-MEK combination therapy. Cancer Discov2016;6:594–600.
WhitePSPudusseriALeeSLEtonO. Intermittent dosing of dabrafenib and trametinib in metastatic BRAFV600E mutated papillary thyroid cancer: two case reports. Thyroid2017;27:1201–1205.
MoschettaMMakGHauserJ. Dabrafenib and trametinib activity in a patient with BRAF V600E mutated and microsatellite instability high (MSI-H) metastatic endometrial cancer. Exp Hematol Oncol2017;6:1.
NardiVSadowPMJuricD. Detection of novel actionable genetic changes in salivary duct carcinoma helps direct patient treatment. Clin Cancer Res2013;19:480–490.
SmalleyKSLioniMDalla PalmaM. Increased cyclin D1 expression can mediate BRAF inhibitor resistance in BRAF V600E-mutated melanomas. Mol Cancer Ther2008;7:2876–2883.
NazarianRShiHWangQ. Melanomas acquire resistance to B-RAF(V600E) inhibition by RTK or N-RAS upregulation. Nature2010;468:973–977.
LitoPSaborowskiAYueJ. Disruption of CRAF-mediated MEK activation is required for effective MEK inhibition in KRAS mutant tumors. Cancer Cell2014;25:697–710.
CohenRBDelordJPDoiT. Preliminary results for the advanced salivary gland carcinoma cohort of the phase 1b KEYNOTE-028 study of pembrolizumab [abstract]. J Clin Oncol2016;34(Suppl):Abstract 6017.