Larotrectinib in TRK fusion differentiated thyroid carcinoma: updated trial data

Area of Science:

• Oncology
• Pharmacology
• Genetics

Background:

• Larotrectinib is a first-in-class TRK inhibitor for TRK fusion cancers.
• Previous studies showed larotrectinib's efficacy in advanced TRK fusion thyroid carcinoma (TC).

Purpose of the Study:

• To report updated pooled analyses of larotrectinib in TRK fusion differentiated TC (DTC).
• To assess long-term outcomes, including overall response rate (ORR), duration of response (DoR), progression-free survival (PFS), and overall survival (OS).

Main Methods:

• Pooled analysis of 3 phase 1-2 clinical trials including 24 patients with TRK fusion DTC.
• Independent Review Committee (IRC) assessment of ORR per RECIST v1.1.
• Long-term follow-up for DoR, PFS, OS, and safety.

Main Results:

• IRC-assessed ORR was 79% (95% CI 58-93), with 13% complete responses.
• Median DoR was 35 months (95% CI 22-NE) and median PFS was 44 months (35-NE).
• The 6-year OS rate was 71% (95% CI 50-91), with 6 patients remaining on treatment.
• Treatment-related adverse events (TRAEs) were predominantly Grade 1/2, with no permanent discontinuations due to TRAEs.

Conclusions:

• Larotrectinib demonstrates durable disease control and extended survival in advanced TRK fusion DTC.
• The drug maintains a favorable long-term safety profile in this patient population.
• Larotrectinib is a viable systemic therapy option for patients with advanced TRK fusion DTC.