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Creative Treatment Approach to Advanced Salivary Gland Cancer With ETV6-NTRK3 Fusion: Case Study

By: Julia Fiederlein
Posted: Thursday, August 19, 2021

A case of ETV6-NTRK3 fusion–positive secretory carcinoma of the minor salivary glands, which ultimately responded to treatment with the small-molecule TRK inhibitor larotrectinib, was described by Jong Chul Park, MD, of Massachusetts General Hospital and Harvard Medical School, Boston, and colleagues in the journal Cancer Reports. This patient profile underscores the importance of accurate diagnosis and molecular testing.

“Secretory carcinoma is a more recently described subtype of salivary gland carcinoma that may pose diagnostic challenges,” the investigators remarked. “[It] frequently harbors NTRK fusions that may successfully be targeted by TRK inhibitors in advanced disease.”

A 56-year-old woman presented with a chronic sore throat. Laryngoscopy revealed a malignant mass originating from the base of the tongue; histopathologic analyses detected diffuse positivity for cytokeratin 7; weak, nonspecific staining for GATA3 and estrogen receptor; and negative staining for PAX-8, CDX-2, TTF1, p40, and cytokeratin 5/6. The patient was subsequently diagnosed with cT2N2cM0 adenocarcinoma with papillary features. She underwent debulking surgery followed by definitive chemoradiation therapy with carboplatin plus paclitaxel weekly and radiotherapy, with a cumulative dose of 70 Gy in 35 fractions; however, after the completion of chemoradiation therapy, possible persistent disease was detected.

After further testing, the mass was diagnosed as a high-grade secretory carcinoma. As an alternative to salvage surgery, which may have resulted in significant swallowing and speech function impairment, the patient initiated targeted therapy with larotrectinib against an identified ETV6-NTRK3 gene fusion. This TRK inhibitor was found to be well tolerated, with no adverse serologic features reported. In addition, the patient experienced a durable complete response while maintaining good swallowing and speech function.

Disclosure: For full disclosures of the study authors, visit onlinelibrary.wiley.com.



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