Biomarker NTRK Coverage from Every Angle

Use of Larotrectinib for in Sarcoma of the Chest: Case Study Focused on TMTC2-NTRK3 Fusion

By: Cordi Craig, MS
Posted: Thursday, December 16, 2021

Undifferentiated high-grade pleomorphic sarcoma is a rare, highly invasive soft-tissue sarcoma that often presents late due to an absence of early symptoms. Previous studies have suggested that the TRK inhibitor larotrectinib may be of benefit in patients with locally advanced and metastatic solid tumors. In a case study report, Zhengfu Fan, MD, of Peking University, Beijing, China, and colleagues identified a novel TMTC2-NTRK3 fusion–positive tumor in a patient with this rare sarcoma of the chest who responded to larotrectinib therapy. The research was published in Research Square as a preliminary report and has not undergone peer review.   

In May 2019, a 69-year-old man presented with a mass nodule on the left chest wall. The research team used next-generation sequencing to determine potential therapeutic options and detected a novel TMTC2-NTRK3 fusion in the surgical tissue. Pan-TRK immunostaining and NTRK break-apart fluorescence in situ hybridization revealed a strong fusion-positive tumor.

Following diagnosis, the patient received four cycles of postoperative radiotherapy. The patient did not report nausea, vomiting, abdominal pain, diarrhea, fever, or exertion and was discharged from the hospital. After 7 months, CT scans revealed multiple metastases in the lungs. In July 2020, the patient was treated with larotrectinib; after 3 months, no noticeable adverse reactions were reported. After 6 months of larotrectinib treatment, the patient reported stable disease, although the metastases in both lungs were enlarged.

“This report broadens the spectrum of NTRK fusions in undifferentiated high-pleomorphic sarcoma of the chest and highlights a new target for treatment,” the researchers concluded.

Disclosure: The study authors reported no conflicts of interest.

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