Introduction: Treatments targeting oncogenic drivers have demonstrated high response rates and improved outcomes in a variety of tumour types. Neurotrophic tropomyosin receptor kinase (NTRK) rearrangements have been described in most solid tumours however, the frequency in non-small cell lung cancer (NSCLC) is not well established.
Methods: This is a retrospective, single-site study in which archival tissue from histologically diagnosed NSCLC between 2018-2020 was screened by immunohistochemistry (IHC) for NTRK rearrangements using the VENTANA® pan-TRK (EPR17341) assay. IHC-positive or equivocal cases were confirmed by Fluorescent in-situ Hybridisation (FISH). Correlative clinicopathologic parameters were also collected.
Results: Analysis of 289 samples was undertaken. For the entire cohort, the median age was 70.9 years (range 35 – 93 years) with 42% female and 77% smokers. Majority of patients had stage IV disease (83%) and tumours of adenocarcinoma histology (69%). Of the 289 samples analysed, nine (3%) samples were IHC-positive and sent for FISH analysis. Of the nine cases the median age of patients was 74.9 years (range 44 – 88 years), 33% female and 71% smokers. Six (75%) cases had adenocarcinoma histology, and one each were of squamous cell carcinoma, large-cell neuroendocrine and NOS histologies respectively. PDL1 expression was <50% in 78% (7/9) cases. Concurrent mutations were detected in 44% (4/9) cases, including EGFR mutations and MET amplification. In 8/9 cases staining was cytoplasmic, with one case demonstrating paranuclear dot-like staining. Confirmatory FISH analysis is underway.
Conclusion: NTRK fusions were not uncommon and detected in all NSCLC histologies as well as with concurrent mutations.