Survival Outcomes of Patients With Tropomyosin Receptor Kinase Fusion-Positive Cancer Receiving Larotrectinib Versus Standard of Care - A Matching-Adjusted Indirect Comparison Using Real-World Data

Sep 24, 2026

Larotrectinib, a highly specific TRK inhibitor, showed high response rates in prior single-arm trials, yet comparative effectiveness versus standard-of-care (SoC) regimens in routine practice remained limited before broad TRK use. A matching-adjusted indirect comparison balanced population characteristics to compare overall survival (OS) between larotrectinib and non–TRK-inhibitor SoC using individual patient data from three trials and real-world data from Flatiron Health/Foundation Medicine. Results indicated longer median OS with larotrectinib and a substantially reduced death risk after matching.

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original reports TARGETED DRUG THERAPY Survival Outcomes of Patients With Tropomyosin Receptor Kinase Fusion-Positive Cancer Receiving Larotrectinib Versus Standard of Care: A Matching-Adjusted Indirect Comparison Using Real-World Data Carsten Bokemeyer, MD1; Noman Paracha, MSc2; Ulrik Lassen, MD, PhD3; Antoine Italiano, MD4; Sean D. Sullivan, PhD5; Marisca Marian, MD2; Nicoletta Brega, MD2; and Jesus Garcia-Foncillas, MD, PhD6 abstract PURPOSE Larotrectinib, a highly speciﬁc tropomyosin receptor kinase (TRK) inhibitor, previously demonstrated high response rates in single-arm trials of patients with TRK fusion-positive cancer, but there are limited data on comparative effectiveness against standard-of-care (SoC) regimens used in routine health care practice, before widespread adoption of TRK inhibitors as SoC for TRK fusion-positive cancers. Matching-adjusted indirect comparison, a validated methodology that balances population characteristics to facilitate cross-trial comparisons, was used to compare the overall survival (OS) of larotrectinib versus non–TRK-inhibitor SoC. MATERIALS AND METHODS Individual patient data from three larotrectinib trials ([ClinicalTrials.gov](ClinicalTrials.gov) identiﬁers: NCT02122913 , NCT02637687, and NCT02576431) were compared with published aggregate real-world data from patients with locally advanced/metastatic TRK fusion-positive cancer identiﬁed in the Flatiron Health/ Foundation Medicine database. OS was deﬁned as the time from advanced/metastatic disease diagnosis to death. After matching population characteristics, the analyses included (1) a log-rank test of equality to test whether the two groups were similar before larotrectinib initiation; and (2) estimation of treatment effect of larotrectinib versus non–TRK-inhibitor SoC. These analyses are limited to prognostic variables available in realworld data. RESULTS Eighty-ﬁve larotrectinib patients and 28 non-TRK-inhibitor SoC patients were included in the analyses. After matching, log-rank testing showed no difference in baseline characteristics between the two groups (P = .31) . After matching, larotrectinib was associated with a 78% lower risk of death, compared with non–TRK-inhibitor SoC (adjusted hazard ratio,0 .22 [95% CI, 0 .09 to0 .52]; P = .001);median OS was39 . 7months (95%CI: 16 .4, NE [not estimable]) for larotrectinib and 10 .2 months (95% CI: 7 .2, 14 . 1) for SoC. CONCLUSION Matching-adjusted indirect comparison analyses suggest longer OS with larotrectinib, compared with non–TRK-inhibitor SoC, in adult patients with TRK fusion-positive cancer. JCO Precis Oncol 7:e2200436 . © 2023 by American Society of Clinical Oncology Creative Commons Attribution Non-Commercial No Derivatives 4.0 License ASSOCIATED CONTENT Appendix Author affiliationsand support information (if applicable) appear atthe end of this article. Accepted on November 21, 2022 and published at [ascopubs.org/journal/](ascopubs.org/journal/)[ ](ascopubs.org/journal/)po on January 23, 2023: DOI [https://doi](https://doi). org/10.1200/PO.22 . 00436 INTRODUCTION Neurotrophic receptor tyrosine kinase genes (NTRK1,2,3) encode tropomyosin receptor kinases (TRK) that regulate development of neuronal function. Chromosomal rearrangements can result in somatic NTRK gene fusions whose encoded TRK fusion proteins are constitutively active/overexpressed and drive oncogenesis.1 Such fusions occur at low frequency in pediatric and adult cancers of the lung, breast, and GI, and in melanomasand sarcomas, and are enriched in infantile ﬁbrosarcoma, secretory carcinoma of the salivary gland, secretory breast carcinoma, and cellular congenital mesoblastic nephroma.2-8 Larotrectinib is a highly selective, potent, CNS-active, orally administered, small-molecule, TRK inhibitor, approved in the United States (2018) and European Union (2019), on the basis of the ﬁndings from three multicenter, single-arm, clinical trials of patients with locally advance

FAQs

What study question does the document address?

It compares overall survival of larotrectinib versus non–TRK-inhibitor standard of care in adult patients with TRK fusion-positive cancer using a matching-adjusted indirect comparison with real-world data.

How were the treatment groups compared?

Individual patient data from three larotrectinib trials were matched to aggregate real-world data in the Flatiron Health/Foundation Medicine database, followed by log-rank testing and treatment effect estimation.

What were the main survival outcomes after matching?

After matching, larotrectinib was associated with a 78% lower risk of death versus non–TRK-inhibitor SoC, with median OS of 39.7 months versus 10.2 months, respectively.

Sep 24, 2026

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