Document Type

Article

Publication Date

4-1-2025

Comments

This article is the author's final published version in JCO Precision Oncology, Volume 9, April 2025, Article number e2400500.

The published version is available at https://doi.org/10.1200/PO-24-00500.

Copyright © 2025 by American Society of Clinical Oncology

Abstract

PURPOSE: Neurotrophic tyrosine receptor kinase gene fusions are oncogenic drivers of various solid tumors. Larotrectinib is a highly selective tropomyosin receptor kinase (TRK) inhibitor approved for patients with TRK fusion cancer on the basis of single-arm trials. This study was a matched comparative effectiveness study of larotrectinib in clinical trials versus standard of care (SOC) in the real-world (RW) setting.

METHODS: Adult patients with advanced/metastatic TRK fusion non-small cell lung cancer, colorectal cancer, soft tissue sarcoma, thyroid cancer, or salivary gland carcinoma were included. Deduplicated data from RW patients were from US and ex-US data sources. Patients in the larotrectinib cohort (pooled data from three trials, ClinicalTrials.gov identifiers: NCT02122913, NCT02576431, and NCT02637687) were matched 1:1 to RW patients on the basis of tumor type and line of therapy (LOT). A propensity score (weighting) model was used to balance key characteristics between cohorts. The primary outcome was overall survival (OS).

RESULTS: In total, 164 patients were matched 1:1 on tumor type and LOT (82 in each cohort). Balance in the baseline covariates was achieved after weighting. Larotrectinib-treated patients had longer OS (median, not reached [NR] v 37.2 months; hazard ratio [HR], 0.44 [95% CI, 0.23 to 0.83]), time to next treatment (median, NR v 10.6 months; HR, 0.22 [95% CI, 0.13 to 0.38]), duration of therapy (median, 30.8 v 3.4 months; HR, 0.23 [95% CI, 0.15 to 0.33]), and progression-free survival (median, 36.8 v 5.2 months; HR, 0.29 [95% CI, 0.18 to 0.46]) compared with RW patients after propensity score weighting.

CONCLUSION: In TRK fusion cancers, treatment with larotrectinib was associated with longer OS and prolonged time to event compared with SOC in all categories measured. These RW data provide context to support larotrectinib effectiveness in this population.

Creative Commons License

Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.

PubMed ID

40267388

Language

English

Download

Share

COinS