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

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.