Support

Clinicopathologic Features of Non–Small-Cell Lung Cancer Harboring an NTRK Gene Fusion

Journal of Clinical Oncology Precision Oncology | July, 2018

Anna F. Farago, Martin S. Taylor, Robert C. Doebele, Viola W. Zhu, Shivaani Kummar, Alexander I. Spira, Theresa A. Boyle, Eric B. Haura, Maria E. Arcila, Ryma Benayed, Dara L. Aisner, Nora K. Horick, Jochen K. Lennerz, Long P. Le, A. John Iafrate, Sai-Hong I. Ou, Alice T. Shaw, Mari Mino-Kenudson, and Alexander Drilon

Purpose

Gene rearrangements that involve NTRK1/2/3 can generate fusion oncoproteins that contain the kinase domains of TRKA/B/C, respectively. These fusions are rare in non–small-cell lung cancer (NSCLC), with frequency previously estimated to be < 1%. Inhibition of TRK signaling has led to dramatic responses across tumor types with NTRK fusions. Despite the potential benefit of identifying these fusions, the clinicopathologic features of NTRK fusion-positive NSCLCs are not well characterized.

Methods

We compiled a database of patients with NSCLCs that harbor NTRK fusions. We characterized clinical, molecular, and histologic features with central review of histology.

Results

We identified 11 patients with NSCLCs that harbor NTRK gene fusions verified by next-generation sequencing (NGS) and with available clinical and pathologic data. Fusions involved NTRK1 (n = 7) and NTRK3 (n = 4), with five and two distinct fusion partners, respectively. Fifty-five percent of cohort patients were male with a median age at diagnosis of 47.6 years (range, 25.3 to 86.0 years) and a median smoking history of 0 pack-years (range, 0 to 58 pack-years). Seventy-three percent of patients had metastatic disease at diagnosis. No concurrent alterations in KRAS, EGFR, ALK, ROS1, or other known oncogenic drivers were identified. Nine patients had adenocarcinoma, including two with invasive mucinous adenocarcinoma and one with adenocarcinoma with neuroendocrine features; one had squamous cell carcinoma; and one had neuroendocrine carcinoma. By collating data on 4,872 consecutively screened, unique patients with NSCLC, we estimate a frequency of NTRK fusions in NSCLC of 0.23% (95% CI, 0.11% to 0.40%).

Conclusion

NTRK fusions occur in NSCLCs across sexes, ages, smoking histories, and histologies. Given the potent clinical activity of TRK inhibitors, we advocate that all NSCLCs be screened for NTRK fusions by using a multiplexed next-generation sequencing (NGS)–based fusion test.

This website stores cookies on your computer. These cookies are used to improve your website and provide more personalized services to you, both on this website and through other media. To find out more about the cookies we use, see our Privacy Policy.

We won’t track your information when you visit our site. But in order to comply with your preferences, we’ll have to use just one tiny cookie so that you’re not asked to make this choice again.