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Profiling Patients With NTRK Gene Fusion–Positive Cancer: UK Genomes Project

By: Emily Rhode
Posted: Thursday, September 29, 2022

John Bridgewater, MBBS, PhD, of University College, London, and colleagues evaluated the overall survival and tumor oncogenomics of patients who have solid tumors with and without NTRK gene fusions. Published in Cancer Treatment and Research Communications, these study findings demonstrated that NTRK gene fusions are the primary oncogenic drivers in tumors that contain them, and the presence or absence of such gene fusions did not seem to statistically impact survival.

“This highlights the importance of NTRK gene fusions as actionable drug targets and emphasizes the need for widespread adoption of broad panel genomic testing in routine oncology clinical practice,” the investigators concluded.

A total of 15,223 patients in the Genomics England 100,000 Genomes Project database were retrospectively analyzed, and 38 patients were identified as having NTRK gene fusions (among them were 9 colorectal cancers, 9 breast cancers, and 7 sarcomas). Patients had not received prior TRK inhibitors.

For primary analysis of overall survival, 18 patients who tested positive for NTRK gene fusions were identified from the database and matched with 72 patients who tested negative for NTRK gene fusions. Sensitivity analysis was also conducted using 31 patients with NTRK gene fusion–positive tumors matched with 124 with NTRK gene fusion–negative tumors. Matched analysis of biomarkers included 3,131 patients with NTRK gene fusion–positive tumors matched with 124 with NTRK gene fusion–negative tumors, and sensitivity analysis included 38 patients with NTRK gene fusion–positive tumors matched with 962 with NTRK gene fusion–negative tumors.

Median overall survival was not reached for either group. The difference between the 12-month overall survival rate in the NTRK gene fusion–positive and fusion–negative groups was not statistically significant, at 94% and 96%, respectively. Sensitivity analysis showed a KRAS mutation in two patients with NTRK gene fusion–positive tumors, and the tested oncogenic drivers were detected in 184 patients with NTRK gene fusion–negative tumors (19%). Matched biomarker analysis identified one KRAS mutation in a patient with an NTRK gene fusion–positive tumor, and the tested oncogenic drivers were found in 33 patients with NTRK gene fusion–negative tumors (26.6%).

Disclosure: For full disclosures of the study authors, visit sciencedirect.com.


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