OBJECTIVES: Neurotrophic receptor tyrosine kinase (NTRK) gene fusions are rare in solid tumors (<0.35%) yet incidence varies widely across cancer types. The first TRK inhibitor (TRKi) was approved by the FDA in November 2018 (larotrectinib) with a second TRKi (entrectinib) approved August 2019. This research aims to describe the TRKi treatment patterns in patients with NTRK-fusion positive solid tumors.

METHODS: Seven academic cancer centers are participating in this ongoing retrospective cohort study. Patients with a solid tumor, a positive NTRK-fusion test result after January 1, 2012, and treated at a participating cancer center were included. Patients treated with a TRKi under clinical trial protocol were excluded. Study variables were abstracted from electronic health records. Treatment patterns were stratified by date of first FDA approved TRKi (pre-TRKi, post-TRKi).

RESULTS: To date, five centers have contributed data for a total of 45 patients meeting eligibility with 67% (n=30) having metastatic disease. Most patients received systemic therapy (n=36, 80%) during follow-up with 58% (n=21) of patients treated in the post-TRKi period, of whom 90% (n=19) received a TRKi. TRKis were commonly initiated in the first (n=7, 37%) or second-line (n=6, 32%) settings. The median (95% CI) duration of therapy (DOT) was 644 (89-not reached) days for TRKi use (n=7) and 122 (49-363) days for all other first-line therapies (n=29) (p=0.21). Median DOT was not reached for second-line TRKi use. TRKi was initiated immediately following the NTRK-fusion positive test result for 53% of patients (n=10) or was the next option following current therapy for 16% (n=3) patients. No patient received multiple TRKi’s.

CONCLUSIONS: Real-world uptake of TRK inhibitors is notable at academic cancer centers, especially in early lines of therapy. There is an early trend for greater DOT with TRKi use across a range of solid tumors in the first-line setting compared to other systemic treatments.