Real-World Evidence for Oncology Patients With Rare <i>NTRK</i> Gene Fusions: Final Results From the German Multicenter Patient Cohort Study REALTRK.

Abstract

TRK inhibitors (TRKis) have transformed the therapeutic landscape for patients with neurotrophic tyrosine receptor kinase (<i>NTRK</i>) 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 <i>NTRK</i> fusion-positive cancers. The REALTRK registry was a multicenter cohort study that included adults with advanced solid tumors harboring <i>NTRK1</i>/<i>2</i>/<i>3</i> fusions, from Germany and Switzerland. Both retrospective and prospective data were collected from diverse clinical settings. <i>NTRK</i> fusions had to be diagnosed via validated assays. Of 88 patients screened, 47 adults with advanced <i>NTRK</i> fusion-positive solid tumors were included in the full analysis set. Across all treatment lines after <i>NTRK</i> 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 <i>NTRK</i> 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 <i>NTRK</i> 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 <i>NTRK1</i>/<i>2</i>/<i>3</i> gene fusions.