Efficacy and safety of larotrectinib in patients with TRK fusion-positive thyroid carcinoma

Steven G. Waguespack, Alexander Drilon, Jessica J. Lin, Marcia S. Brose, Ray McDermott, Mohammed Almubarak, Jessica Bauman, Michela Casanova, Anuradha Krishnamurthy, Shivaani Kummar, Serge Leyvraz, Do Youn Oh, Keunchil Park, Davendra Sohal, Eric Sherman, Ricarda Norenberg, Josh D. Silvertown, Nicoletta Brega, David S. Hong, Maria E. Cabanillas

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

Objective: Larotrectinib is a highly selective tropomyosin receptor kinas e (TRK) inhibitor with demonstrated efficacy across various TRK fusion-positive solid tumours. We assessed t he efficacy and safety of larotrectinib in patients with TRK fusion-positive thyroid carcinoma (TC). Methods: We pooled data from three phase I/II larotrectinib clinical trials (NCT02576431, NCT02122913, and NCT02637687). The primary endpoint was the investigator-assessed objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors v1.1. Secondary endpoints i ncluded duration of response (DoR), progression-free survival (PFS), overall survival (OS), and safety. Data cut-off: July 2020. Results: Twenty-nine patients (median age: 60; range: 6-80) with TRK fu sion-positive TC were treated. Tumour histology was papillary (PTC) in 20 (69%) patients, follicular (FTC) in 2 (7%), and anaplastic (ATC) in 7 (24%) patients. Among 28 evaluable patients, ORR was 71% (95% CI: 51-87); best responses were complete response in 2 (7%) patients, partial response in 18 (64%), stable disease in 4 (14%), progressive di sease in 3 (11%), and undetermined in 1 (4%) due to clinical progression prior to the first post-baseline assessment . ORR was 86% (95% CI: 64-97) for PTC/FTC and 29% (95% CI 4-71) for ATC. Median time to response was 1.87 months (range 1.64-3.68). The 24-month DoR, PFS, and OS rates were 81, 69, and 76%, respectively. Treatment-related adv erse events were mainly grades 1-2. Conclusion: In TRK fusion-positive TC, larotrectinib demonstrates rapid an d durable disease control and a favourable safety profile in patients with advanced disease requiring syste mic therapy.

Original languageEnglish (US)
Pages (from-to)631-643
Number of pages13
JournalEuropean journal of endocrinology
Volume187
Issue number1
DOIs
StatePublished - Jun 2022
Externally publishedYes

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

Fingerprint

Dive into the research topics of 'Efficacy and safety of larotrectinib in patients with TRK fusion-positive thyroid carcinoma'. Together they form a unique fingerprint.

Cite this