Using Targeted Therapies for NTRK-Fusion-Positive Thyroid Cancer


Lori Wirth, MD, discusses her experience with NTRK-targeted therapies for patients with thyroid cancer.

Lori Wirth, MD, associate professor of medicine at Harvard Medical School and medical director for the Center for Head and Neck Cancers at Massachusetts General Hospital, discusses her experience with NTRK-targeted therapies for patients with thyroid cancer.

Wirth says that her practice has participated in phase 1 and phase 2 clinical trials of the NTRK inhibitors larotrectinib (Vitrakvi) and entrectinib (Rozlytrek) in patients with NTRK fusions, which are common in thyroid cancer. The FDA approved larotrectinib and entrectinib for patients with any metastatic or unresectable solid tumors and an NTRK fusion, who have no satisfactory alternative treatment. Patients with differentiated thyroid cancer as well as salivary gland tumors are more likely to harbor NTRK fusions.

Patients with iodine-refractory thyroid cancer with an NTRK fusion are candidates for NTRK inhibition. According to Wirth, targeted inhibition does not need to be used immediately if the disease is asymptomatic and is measured to be low volume and slow growing, but it should be considered at disease progression. She says she has continued to use larotrectinib for patients with NTRK fusion-positive thyroid cancer following its approval.


0:08 | In our practice, in our head and neck oncology group, we do use larotrectinib for the treatment of patients with advanced cancers driven by NTRK fusions. We did have the larotrectinib and entrectinib trials open. So we've used both of those 2 therapies for a number of years in our patients, when we were initially enrolling patients in the early phase 1 and 2 trials of larotrectinib and entrectinib. Now that larotrectinib is commercially available, we do use it in our head and neck cancer patient population. We do see patients with advanced differentiated thyroid cancer and then also salivary gland tumors that can occasionally harbor NTRK fusions, particularly ETV6-NTRK3 fusions in salivary gland secretory carcinomas.

1:12 | So when patients with thyroid cancer are identified to harbor an NTRK fusion, we will use therapy when we know that they have iodine-refractory disease and when they have some measurable disease that's growing. Many patients with thyroid cancer will have low-volume disease that grows very slowly. So we don't always need to start therapy right away in patients with very low-volume, asymptomatic, slow-growing disease. But when there's disease progression, that's always a good time to consider whether or not a drug like larotrectinib should be started. But since the clinical trials are no longer enrolling, I have started a number of patients with NTRK fusion-positive thyroid cancer on larotrectinib.

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