Prognosis And Molecular Characteristics Of Patients With Trk Fusion Cancer In The 100,000 Genomes Project.

Abstract Background: NTRK gene fusions are oncogenic drivers in various tumor types. Overall survival (OS) of patients (pts) with tumors harboring NTRK fusions compared to pts without is unknown, and data on co-occurrence of NTRK fusions with other oncogenic drivers are limited.1 Methods: This retrospective study used genomic data generated by the 100,000 Genomes Project with linked clinical data from UK cancer databases. Pts with cancer who had undergone tumor whole genome sequencing between Mar 2016 and Jul 2019 were included. OS of pts with and without NTRK fusions, matched by exact and distance matching with a 1:4 NTRK+:NTRK− ratio, was analyzed by Kaplan-Meier method and Cox regression. Key alterations in ALK, BRAF, EGFR, HER2, KRAS and ROS1, and tumor mutation burden (TMB) and microsatellite instability (MSI), were evaluated along with NTRK gene fusions. Results: Of 15,223 pts analyzed, 38 (0.2%) had NTRK fusions, identified in 11 cancers (Genomics England classification), the most common being breast cancer (n=9), colorectal cancer (CRC; n=9), and sarcoma (n=7). While there was no significant OS difference in pts with and without NTRK fusions, the HR was 1.47 (95% CI 0.39-5.57; Table). Of the tested oncogenic drivers, only KRAS mutation was identified in 2 (5%) pts with an NTRK fusion (both hepatobiliary cancer), while oncogenic driver frequency in pts without NTRK fusions ranged from 0.1-11.6%. High TMB was more common in pts with NTRK fusions than in those without (21% vs 6%), as was high MSI (18% vs 6%); all pts with NTRK fusions and high TMB and/or MSI had CRC. Conclusions: While no statistical difference in OS was observed, there was a trend to higher risk of death in pts with NTRK fusions compared to those without, consistent with a recent US study.1 Co-occurrence of NTRK fusions and other biomarkers was rare, except for high TMB and high MSI in CRC. These results highlight NTRK fusions as actionable biomarkers and emphasize the need for NTRK gene fusion testing. NTRK− (n=72†)NTRK+ (n=18†)Median follow-up (IQR), years2.28 (1.57-2.98)2.01 (1.40-2.97)Median OS (IQR), yearsNE (NE-NE)NE (NE-NE)Landmark OS, % (95% CI)1 year96 (91-100)94 (84-100)2 years94 (89-100)87 (71-100)3 years88 (78-99)87 (71-100)HR (95% CI)1.47 (0.39-5.57)†Only patients with linked clinical data and who were matched were included in the OS analysis.1CI, confidence interval; HR, hazard ratio; IQR, interquartile range; NE, not estimable; NTRK; neurotrophic tyrosine receptor kinase; OS, overall survival.1. Bazhenova L, et al. Clin Cancer Res. 2020;26(12 Suppl 1):09-09. Citation Format: John Bridgewater, Xiaolong Jiao, Mounika Parimi, Clare Flach, Jeran Stratford, Atanas Kamburov, Arndt Schmitz, Jihong Zong, John A. Reeves, Karen Keating, Amanda Bruno, Marc Fellous, Lyudmila Bazhenova. Prognosis and molecular characteristics of patients with TRK fusion cancer in the 100,000 Genomes Project [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 394.