Real-World Evidence for Oncology Patients With Rare NTRK Gene Fusions: Final Results From the German Multicenter...

TRK inhibitors (TRKis) have transformed the therapeutic landscape for patients with neurotrophic tyrosine receptor kinase (NTRK) gene fusion-positive tumors. However, approval of TRKis is based on evidence derived mainly from small, pooled, single-arm clinical trial cohorts. The REALTRK registry aims to describe real-world molecular diagnostic practices, treatment patterns, and clinical outcomes for adult patients with NTRK fusion-positive cancers.

The REALTRK registry was a multicenter cohort study that included adults with advanced solid tumors harboring NTRK1/2/3 fusions, from Germany and Switzerland. Both retrospective and prospective data were collected from diverse clinical settings. NTRK fusions had to be diagnosed via validated assays.

Of 88 patients screened, 47 adults with advanced NTRK fusion-positive solid tumors were included in the full analysis set. Across all treatment lines after NTRK fusion diagnosis, 29 patients received TRKi therapy, eight received non-TRKi therapy, and 10 received no therapy. Lung cancer, colorectal cancer, and soft tissue sarcoma were the most common tumor types. Next-generation sequencing was the primary diagnostic method, with a median turnaround time of 2 weeks. After NTRK fusion diagnosis, TRKi therapy was immediately initiated in 26 patients, of whom 13 received TRKi as first-line treatment in the advanced/metastatic setting. About half of the patients responded to TRKi treatment as the first treatment line after NTRK fusion diagnosis (46.2%), with an overall response rate of 46.2% and a disease control rate of 73.1%. The median progression-free survival was 15.7 months, and the overall survival was 27.6 months in TRKi-treated patients.

The REALTRK registry provides important real-world insights into the patient path of adult patients with locally advanced or metastatic solid tumors harboring NTRK1/2/3 gene fusions.