Larotrectinib in TRK fusion differentiated thyroid carcinoma: updated trial data.

Authors

• Steven G Waguespack
• Marcia S Brose
• Jessica J Lin
• Ray McDermott
• Mohammed Almubarak
• Jessica Bauman
• Michela Casanova
• Shivaani Kummar
• Se-Hoon Lee
• Damian T Rieke
• Do-Youn Oh
• Changsong Qi
• Natascha Neu
• Domnita-Ileana Burcoveanu
• Chiara E Mussi
• Alexander Drilon
• David S Hong
• Maria E Cabanillas

Publication/Presentation Date

8-1-2026

Abstract

Larotrectinib is a first-in-class, highly selective, central nervous system-active tropomyosin receptor kinase (TRK) inhibitor approved for tumour-agnostic use in TRK fusion cancer. It has previously demonstrated rapid and durable disease control and favourable safety in patients with advanced TRK fusion thyroid carcinoma (TC). After an additional 4 years of follow-up with the inclusion of two additional patients, and utilising an independent review committee (IRC) to assess overall response rate (ORR), we report updated pooled analyses from three phase 1-2 larotrectinib clinical trials, focusing only on patients with TRK fusion differentiated TC (DTC). The primary endpoint was the IRC-determined ORR per RECIST v1.1. Duration of response (DoR), progression-free survival (PFS), overall survival (OS) and safety were also assessed. Twenty-four patients (papillary TC, n = 21; follicular TC, n = 2; poorly DTC, n = 1) were included (data cut-off: 20 July 2024). ORR was 79% (95% confidence interval (CI): 58-93); best responses were complete response in 3 (13%) patients, partial response in 16 (67%), stable disease in 3 (13%), progressive disease in 1 (4%) and not evaluable in 1 (4%). Median DoR and PFS were 35 (95% CI: 22-not estimable (NE)) and 44 (95% CI: 35-NE) months, respectively; 6-year OS rate was 71% (95% CI: 50-91). Six patients remained on treatment. Treatment-related adverse events (TRAEs) were mainly grade 1/2; no patients permanently discontinued treatment due to TRAEs. Larotrectinib continues to demonstrate durable disease control, extended survival and a favourable long-term safety profile in patients with advanced TRK fusion DTC requiring systemic therapy.

Volume

33

Issue

8

ISSN

1479-6821

Published In/Presented At

Waguespack, S. G., Brose, M. S., Lin, J. J., McDermott, R., Almubarak, M., Bauman, J., Casanova, M., Kummar, S., Lee, S. H., Rieke, D. T., Oh, D. Y., Qi, C., Neu, N., Burcoveanu, D. I., Mussi, C. E., Drilon, A., Hong, D. S., & Cabanillas, M. E. (2026). Larotrectinib in TRK fusion differentiated thyroid carcinoma: updated trial data. Endocrine-related cancer, 33(8), e250531. https://doi.org/10.1530/ERC-25-0531

Disciplines

Medicine and Health Sciences

PubMedID

42454511

Department(s)

Hematology-Medical Oncology Division

Document Type

Article