Document Type
Article
Publication Date
8-5-2026
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.
Recommended Citation
Waguespack, Steven; Brose, Marcia; Lin, Jessica J; McDermott, Ray; Almubarak, Mohammed; Bauman, Jessica; Casanova, Michela; Kummar, Shivaani; Lee, Se-Hoon; Rieke, Damian; Oh, Do-Youn; Qi, Changsong; Neu, Natascha; Burcoveanu, Domnita-Ileana; Mussi, Chiara; Drilon, Alexander; Hong, David; and Cabanillas, Maria, "Larotrectinib in TRK Fusion Differentiated Thyroid Carcinoma: Updated Trial Data" (2026). Department of Medical Oncology Faculty Papers. Paper 349.
https://jdc.jefferson.edu/medoncfp/349
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
PubMed ID
42454511
Language
English
Comments
This article is the author’s final published version in Endocrine-Related Cancer, Volume 33, Issue 8, 2026, Article number e250531.
The published version is available at https://doi.org/10.1530/ERC-25-0531. Copyright © 2026 the author(s).