Clinical characteristics and treatment patterns of patients with <i>NTRK</i> fusion-positive solid tumors: A multisite cohort study at US academic cancer centers.

Abstract

Neurotrophic tyrosine receptor kinase (<i>NTRK</i>) gene fusions are rare oncogenic drivers prevalent in 0.3% of solid tumors. They are most common in salivary gland cancer (2.6%), thyroid cancer (1.6%), and soft-tissue sarcoma (1.5%). Currently, there are 2 US Food and Drug Administration-approved targeted therapies for <i>NTRK</i> gene fusions: larotrectinib, approved in 2018, and entrectinib, approved in 2019. To date, the real-world uptake of tyrosine receptor kinase inhibitor (TRKi) use for <i>NTRK</i>-positive solid tumors in academic cancer centers remains largely unknown. To describe the demographics, clinical and genomic characteristics, and testing and treatment patterns of patients with <i>NTRK</i>-positive solid tumors treated at US academic cancer centers. This was a retrospective chart review study conducted in academic cancer centers in the United States. All patients diagnosed with an <i>NTRK</i> fusion-positive (<i>NTRK</i>1, <i>NTRK</i>2, <i>NTRK</i>3) solid tumor (any stage) and who received cancer treatment at participating sites between January 1, 2012, and July 1, 2023, were included in this study. Patient demographics, clinical characteristics, genomic characteristics, <i>NTRK</i> testing data, and treatment patterns were collected from electronic medical records and analyzed using descriptive statistics as appropriate. In total, 6 centers contributed data for 55 patients with <i>NTRK</i>-positive tumors. The mean age was 49.3 (SD = 20.5) years, 51% patients were female, and the majority were White (78%). The median duration of time from cancer diagnosis to <i>NTRK</i> testing was 85 days (IQR = 44-978). At the time of <i>NTRK</i> testing, 64% of patients had stage IV disease, compared with 33% at cancer diagnosis. Prevalent cancer types in the overall cohort included head and neck (15%), thyroid (15%), brain (13%), lung (13%), and colorectal (11%). <i>NTRK</i>1 fusions were most common (45%), followed by <i>NTRK</i>3 (40%) and <i>NTRK</i>2 (15%). Across all lines of therapy, 51% of patients (n = 28) received a TRKi. Among TRKi-treated patients, 71% had stage IV disease at TRKi initiation. The median time from positive <i>NTRK</i> test to initiation of TRKi was 48 days (IQR = 9-207). TRKis were commonly given as first-line (30%) or second-line (48%) therapies. Median duration of therapy was 610 (IQR = 182-764) days for TRKi use and 207.5 (IQR = 42-539) days for all other first-line therapies. This study reports on contemporary real-world <i>NTRK</i> testing patterns and use of TRKis in solid tumors, including time between <i>NTRK</i> testing and initiation of TRKi therapy and duration of TRKi therapy.