Clinical characteristics and treatment patterns of patients with NTRK fusion-positive solid tumors: A multisite cohort study at US academic cancer centers. J Manag Care Spec Pharm 2024 Jul;30(7):672-683
Date
07/01/2024Pubmed ID
38950155Pubmed Central ID
PMC11217863DOI
10.18553/jmcp.2024.30.7.672Scopus ID
2-s2.0-85197554044 (requires institutional sign-in at Scopus site) 4 CitationsAbstract
BACKGROUND: Neurotrophic tyrosine receptor kinase (NTRK) 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 NTRK 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 NTRK-positive solid tumors in academic cancer centers remains largely unknown.
OBJECTIVE: To describe the demographics, clinical and genomic characteristics, and testing and treatment patterns of patients with NTRK-positive solid tumors treated at US academic cancer centers.
METHODS: This was a retrospective chart review study conducted in academic cancer centers in the United States. All patients diagnosed with an NTRK fusion-positive (NTRK1, NTRK2, NTRK3) 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, NTRK testing data, and treatment patterns were collected from electronic medical records and analyzed using descriptive statistics as appropriate.
RESULTS: In total, 6 centers contributed data for 55 patients with NTRK-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 NTRK testing was 85 days (IQR = 44-978). At the time of NTRK 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%). NTRK1 fusions were most common (45%), followed by NTRK3 (40%) and NTRK2 (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 NTRK 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.
CONCLUSIONS: This study reports on contemporary real-world NTRK testing patterns and use of TRKis in solid tumors, including time between NTRK testing and initiation of TRKi therapy and duration of TRKi therapy.
Author List
Willis C, Au T, Hejazi A, Griswold C, Schabath MB, Thompson J, Malhotra J, Federman N, Ko G, Appukkuttan S, Warnock N, Kong SX, Hocum B, Brixner D, Stenehjem DAuthor
Jonathan R. Thompson MD Associate Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Academic Medical CentersAdult
Aged
Benzamides
Cohort Studies
Female
Humans
Indazoles
Male
Membrane Glycoproteins
Middle Aged
Neoplasms
Oncogene Proteins, Fusion
Protein Kinase Inhibitors
Pyrazoles
Pyrimidines
Receptor, trkA
Receptor, trkB
Receptor, trkC
Retrospective Studies
United States
Young Adult
