Estimating the Prognostic Value of the NTRK Fusion Biomarker for Comparative Effectiveness Research in The Netherlands

Irene Santi*, Heleen Vellekoop, Matthijs M Versteegh, Simone A Huygens, Winand N.M. Dinjens, Maureen Rutten van Mölken

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

Objectives: 

We evaluated the prognostic value of the neurotrophic tyrosine receptor kinase (NTRK) gene fusions by comparing the survival of patients with NTRK+ tumours with patients without NTRK+ tumours. 

Methods: 

We used genomic and clinical registry data from the Center for Personalized Cancer Treatment (CPCT-02) study containing a cohort of cancer patients who were treated in Dutch clinical practice between 2012 and 2020. We performed a propensity score matching analysis, where NTRK+ patients were matched to NTRK− patients in a 1:4 ratio. We subsequently analysed the survival of the matched sample of NTRK+ and NTRK− patients using the Kaplan–Meier method and Cox regression, and performed an analysis of credibility to evaluate the plausibility of our result. 

Results:

Among 3556 patients from the CPCT-02 study with known tumour location, 24 NTRK+ patients were identified. NTRK+ patients were distributed across nine different tumour types: bone/soft tissue, breast, colorectal, head and neck, lung, pancreas, prostate, skin and urinary tract. NTRK fusions involving the NTRK3 gene (46%) and NTRK1 gene (33%) were most common. The survival analysis rendered a hazard ratio (HR) of 1.44 (95% CI 0.81–2.55) for NTRK+ patients. Using the point estimates of three prior studies on the prognostic value of NTRK fusions, our finding that the HR is > 1 was deemed plausible. 

Conclusions: 

NTRK+ patients may have an increased risk of death compared with NTRK− patients. When using historic control data to assess the comparative effectiveness of TRK inhibitors, the prognostic value of the NTRK fusion biomarker should therefore be accounted for.

Original languageEnglish
Pages (from-to)319-328
Number of pages10
JournalMolecular Diagnosis and Therapy
Volume28
Issue number3
DOIs
Publication statusPublished - May 2024

Bibliographical note

Publisher Copyright:
© The Author(s) 2024.

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