Complete response to larotrectinib treatment in a patient with papillary thyroid cancer harboring an ETV6-NTRK3 gene fusion

Abstract

Larotrectinib, a highly selective TRK inhibitor, was administered to a patient with rapidly progressing radioactive iodine-refractory papillary NTRK3 fusion-positive thyroid cancer. The patient achieved a durable (sustained for 11 months) complete response after 2 months of treatment and complete intracranial responses in metastatic brain lesions after 7 months of treatment. Larotrectinib may provide a therapeutic route for patients with RAI-R-differentiated thyroid cancer who might otherwise have few treatment options.

Keywords: iodine uptake and iodine metabolism; thyroid cancer‐clinical; thyroid cancer‐genetics.

FIGURE 1

Treatment pathway of a patient with PTC who progressed on sorafenib and lenvatinib, and who achieved a complete response with larotrectinib treatment. AE, adverse event; PTC, papillary thyroid cancer; RAI, radioactive iodine

FIGURE 2

A diagnosis of RAI‐R thyroid cancer was based on the presence of multiple metastatic sites revealed with ¹⁸F‐FDG uptake in the first PET/CT scan conducted in April 2018. Diffuse lesions in soft and muscular tissues, multiple ¹⁸F‐FDG uptake in bones, and a large target lesion in the left lung were observed (arrow) (transverse view). ¹⁸ F‐FDG, 2‐deoxy‐2‐[fluorine‐18] fluoro‐D‐glucose; PET/CT, positron emission tomography/computed tomography; RAI‐R, radioiodine refractory

FIGURE 3

The extent of metastatic disease following treatment was determined by ¹⁸F‐FDG uptake in the PET/CT scan conducted in August 2019 after 6 months of sorafenib treatment (reduced to 600 mg/day) and 5 months of lenvatinib treatment (20 mg/day). Multiple lymph node metastases were observed in the neck and mediastinum, with multiple secondary lesions in subcutaneous tissues and muscles, the liver, adrenal gland, and right pleura were identified (coronal view). ¹⁸ F‐FDG, 2‐deoxy‐2‐[fluorine‐18] fluoro‐D‐glucose; PET/CT, positron emission tomography/computed tomography

FIGURE 4

After 4 weeks on larotrectinib treatment, an ¹⁸F‐FDG PET/CT scan showed a near‐complete response—only neck lymph node and lung (arrowed) lesions persisted in October 2019 after 4 weeks of larotrectinib (200 mg/day) treatment (transverse view); most lesions had disappeared. ¹⁸ F‐FDG, 2‐deoxy‐2‐[fluorine‐18] fluoro‐D‐glucose; PET/CT, positron emission tomography/computed tomography

FIGURE 5

Complete response after 8 weeks of larotrectinib (200 mg/day) treatment in November 2019. No lesions with ¹⁸F‐FDG uptake were observed during the PET/CT scan. ¹⁸ F‐FDG, 2‐deoxy‐2‐[fluorine‐18] fluoro‐D‐glucose; PET/CT, positron emission tomography/computed tomography

FIGURE 6

Intracranial response of metastatic lesions in the brain following larotrectinib (200 mg/day) treatment. MRI scans show substantial reductions in lesion sizes following 7 months of treatment. MRI, magnetic resonance imaging