Timing of NTRK Gene Fusion Testing and Treatment Modifications Following TRK Fusion Status Among US Oncologists Treating TRK Fusion Cancer.

Abstract

BACKGROUND:

Neurotrophic tyrosine receptor kinase (NTRK) gene fusions are oncogenic drivers with an estimated prevalence of less than 1% across all solid tumors. Tropomyosin receptor kinase inhibitors (TRKis) block the constitutively activated tyrosine receptor kinase (TRK) fusion protein produced in NTRK gene fusion positive (NTRK+) tumors from downstream signaling. Tropomyosin receptor kinase inhibitors are now first-line (1L) or subsequent treatment options for TRK fusion cancers.

OBJECTIVE:

This study assessed timing of NTRK gene fusion testing and treatment modifications among patients with TRK fusion cancers.

PATIENTS AND METHODS:

This was a one-time physician questionnaire with a retrospective, multisite patient chart abstraction of oncology practices in the USA. From June to September 2020, medical oncologists from the Oncology Provider Extended Network (OPEN) who treated patients with NTRK+ advanced/metastatic solid tumors abstracted information into electronic case report forms (eCRFs) for adult patients with advanced/metastatic solid tumors and a NTRK+ tumor test result with a known fusion partner. Use of NTRK testing in routine clinical practice among patients with advanced/metastatic solid tumors was assessed. Data included demographic, clinical, and NTRK gene fusion testing characteristics. Responses were summarized using descriptive statistics.

RESULTS:

Twenty-eight community-based medical oncologists who had managed or treated 148 patients with advanced/metastatic TRK fusion cancer between 01/01/2016 and 12/31/2019 completed the survey. Lung (27%), thyroid (18%), salivary gland (14%), and colorectal (12%) were the most commonly reported tumor types. A majority (68%) tested NTRK status prior to 1L initiation; testing after disease progression on 1L (36%), 2L (25%), and 3L (21%) was also noted. Most oncologists (96%) reported no difficulty interpreting NTRK reports. Nearly all (96%) indicated using next-generation sequencing (NGS) for determining NTRK status. The majority (57%) indicated that age, tumor type, and performance status did not impact NTRK testing decisions. Less than half (46%) include TRKi therapy following NTRK+ determination. NTRK testing guidelines were commonly reviewed by physicians (89%).

CONCLUSION AND RELEVANCE:

Among patients with advanced/metastatic TRK fusion cancer, medical oncologists reported testing for NTRK fusions at diagnosis or prior to 1L. Future research should elucidate why fewer than half of oncologists surveyed (46%) would not use TRKis after NTRK+ status confirmation, assess clinical practices among NTRK+ patients, and characterize treatment patterns and clinical outcomes in real-world settings.

• Authors: Andrew J Klink, Abhishek Kavati, Awa T Gassama, Tom Kozlek, Ajeet Gajra, Ruth Antoine
• Journal: Targeted oncology (Target Oncol) Vol. 17 Issue 3 Pg. 321-328 (05 2022) ISSN: 1776-260X [Electronic] France
• PMID: 35716252 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2022. The Author(s).

Chemical References

• Oncogene Proteins, Fusion
• Protein Kinase Inhibitors
• Tropomyosin
• Receptor Protein-Tyrosine Kinases
• Receptor, trkA

Topics

• Adult
• Gene Fusion
• Humans
• Neoplasms (drug therapy, genetics, pathology)
• Oncogene Proteins, Fusion (genetics)
• Oncologists
• Protein Kinase Inhibitors (therapeutic use)
• Receptor Protein-Tyrosine Kinases (metabolism)
• Receptor, trkA (genetics, metabolism)
• Retrospective Studies
• Tropomyosin (genetics, therapeutic use)