Updated Efficacy and Safety of Larotrectinib in Patients with Advanced Tropomyosin Receptor Kinase (TRK) Fusion Positive Thyroid Carcinoma

Background

• Larotrectinib is a highly selective TRK inhibitor which has shown a 71% overall response rate (ORR) in 28 investigator-evaluable patients with TRK fusion-positive thyroid carcinoma (TC) as of July 2020.
• We report data on an expanded dataset of patients with TRK fusion-positive TC treated with larotrectinib.

Methods

• Patients from 3 larotrectinib clinical trials (NCT02576431, NCT02122913, NCT02637687) were included.
• Larotrectinib was administered at 100mg twice daily.
• Responses were assessed per independent review committee using RECIST version 1.1.

Results

• As of July 2021, 30 patients with TRK fusion-positive TC (medican age, 61.5 years [range, 6-80 years]) were enrolled, including 29 individuals with an additional year of follow-up.
• Seven patients (23%) had recieved 2 prior systemic therapies; 26 patients (87%) had recieved prior radioiodine.
• ORR was 63% (95% CI, 44%-80%). In all, 3 patients (10%) had complete responses, 16 patients (54%) had partial responses, 5 patients (17%) had stable disease (all with target lesion shrinkage), and 4 patients (13%) had progressive disease (3 with anaplastic TC [ATC]); responses in 2 patients (17%) were not determined.
• For patients classified as having differentiated TC (DTC; n = 23), ORR was 78% (95% CI, 56%-93%); for patients classified as having ATC (n = 7), ORR was 14% (95% CI, 0%-58%).
• In all responders, median time to response was 1.9 months, median duration of response (DOR) was 43.3 months (95% CI, 21.6 months to not estimable [NE]), and median follow-up was 28.8 months.
• Median progression-free survival (PFS) was 48.7 months (95% CI, 27.8 months to NE); median follow-up was 34.1 months.
• For DTC, the median DOR, PFS, and OS were 43.3 months, 48.7 months, and not reached, respectively.
• For ATC, the median DOR, PFS, and OS were 3.7, 2.2, and 8.8 months, respectively.
• Treatment-related adverse events (TRAEs) were mostly grade 1 or 2. Grade 3 anemia and decreased lymphocyte count were reported in 2 patinets (7%); none of the patients discontinued treatment due to TRAEs.

Conclusions

• Larotrectinib demonstrated a high ORR, rapid and durable disease control, and an overall favorable safety profile in patients with TRK fusion-positive DTC.
• These data support testing for TRK fusions in patients with advanced TC requiring systemic therapy.

Cabanillas ME, Lin JJ, Brose MS et al. Updated Efficacy and Safety of Larotrectinib in Patients with Advanced Tropomyosin Receptor Kinase (TRK) Fusion Positive Thyroid Carcinoma. Abstract presented at: 2022 American Tyroid Association Annual Meeting, October 19-23, 2022; Abstract# Poster 108. https://www.liebertpub.com/doi/epdf/10.1089/thy.2022.29137.abstracts