Abstract P022: Clinical and genomic characteristics of tropomyosin receptor kinase (TRK) fusion cancer in community oncology practice
Authors: Klink Andrew , Kavati Abhishek , Antoine Ruth , Gassama Awa , Kozlek Tom , Gajra Ajeet 
Published: December 2021

Introduction: NTRK gene fusions have been observed across age groups in a variety of tumor types and are implicated in approximately 1% of all solid tumor cancers. The FDA approved larotrectinib (2018) and entrectinib (2019) for the treatment of TRK fusion cancer in adult and pediatric populations (larotrectinib: all ages; entrectinib: ≥12 years old). Given the rarity of NTRK gene fusions, both approvals were based on trials recruiting small numbers of patients in single arm trials. Characteristics of patients harboring NTRK gene fusions in the real-world setting are limited. This study reports the real-world demographic, clinical, and genomic characteristics in patients harboring an NTRK gene fusion. Methods: A retrospective, observational cohort study of adult patients with a known NTRK gene fusion and diagnosed with any advanced or metastatic solid tumor between January 1, 2016 and December 31, 2019 was conducted. Characteristics and testing patterns were abstracted from patient medical records by 19 medical oncologists (89.5% community-based; 10.5% academic/teaching hospital) across all geographic areas in the US (21.1% Northeast, 10.5% Midwest, 36.8% South, 31.6% West). Descriptive statistics were used to summarize patient characteristics and testing patterns. Results: Among the 110 patients included in the study, the median (range) patient age at advanced/metastatic diagnosis was 62 (39-77) years. The majority of patients (58.2%) were male and white (79.1%). Among the 15 solid tumor types observed, lung (24.5%), cholangiocarcinoma (13.6%), pancreatic (10.9%), and colorectal (10.0%) were reported in at least 10% of the study cohort. Half (50.0%) of patients had an NTRK1 gene fusion, and 27.3% and 20.0% had NTRK3 and NTRK2 gene fusion, respectively. The five most commonly reported NTRK gene fusion partners were ETV6-NTRK3 (13.6%), TPM3-NTRK1 (7.3%), PPL-NTRK1 (4.5%), SQSTM1-NTRK1 (4.5%), and TPM3-NTRK2 (4.5%). Median time from initial cancer diagnosis to NTRK gene fusion testing was 11.5 (interquartile range, 1-149) days. Next generation sequencing was used to identify NTRK gene fusions in 69.1% of patients (8.2% performed as confirmation to immunohistochemistry testing), followed by fluorescent in situ hybridization studies (FISH) in 14.5% of patients and unknown in 16.4% of patients. Conclusion: TRK fusion cancer was most commonly observed in lung, cholangiocarcinoma, pancreatic, and colon cancers. Patients harboring NTRK gene fusions are being identified soon after initial cancer diagnosis across a variety of tumor types and age groups in routine clinical practice. Early detection of NTRK gene fusions can inform the clinician regarding use of TRK inhibitors earlier in the course of disease when indicated.

Citation Format: Andrew Klink, Abhishek Kavati, Ruth Antoine, Awa Gassama, Tom Kozlek, Ajeet Gajra. Clinical and genomic characteristics of tropomyosin receptor kinase (TRK) fusion cancer in community oncology practice [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2021 Oct 7-10. Philadelphia (PA): AACR; Mol Cancer Ther 2021;20(12 Suppl):Abstract nr P022.