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Investigating the natural history and prognostic nature of NTRK gene fusions in solid tumors

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Summary

Background. Several TRK inhibitors have demonstrated clinical efficacy in patients with solid tumors harboring NTRK gene fusions. However, the natural history and prognostic implications of NTRK fusions in solid tumors remain unknown. Methods. A cohort of 77 MD Anderson Cancer Center patients (MDACC) with NTRK gene fusions was identified and retrospectively compared to a second cohort from the Cancer Genome Atlas (TCGA) database. Due to paucity of events in early stage cancers and lack of TCGA data in rare tumors, 25 randomly selected MDACC patients were matched to 122 TCGA patients without NTRK gene fusion. Next we assessed the associations between NTRK gene fusion and overall (OS) and progression-free survivals (PFS). Results. Among the 77 MDACC patients with NTRK gene fusions, 18 NTRK fusion partners were identified. There were insufficient OS events for analysis in the matched cohort. PFS was not significantly different (p = 0.49) between the NTRK-fusion positive MDACC patients (median PFS 786 weeks, 95% CI 317-NE) and the NTRK-fusion negative TCGA patients (median PFS NE). The adjusted hazard ratio comparing TCGA patients to MDACC patients was HR = 0.72 (95% CI: 0.23–2.33), which trended towards a reduced rate of progression or death experienced by TCGA patients. Conclusions. This study did not identify statistically significant associations between NTRK fusion and PFS. Nonsignificant trends estimated increases in the risk of progression or death events for patients with NTRK fusions when compared to matched controls. Our findings help illuminate the influence of NTRK fusions on the natural history of a variety of solid tumors.

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All data generated and analyzed during the current study are available from the corresponding author on reasonable request.

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Funding

This study was funded by National Institute of Health and Bayer Corporation.

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Correspondence to David S. Hong.

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This retrospective study involving human participants was in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The Human Investigation Committee (IRB) of MD Anderson Cancer Center approved this study.

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Zhu, L., Hobbs, B., Roszik, J. et al. Investigating the natural history and prognostic nature of NTRK gene fusions in solid tumors. Invest New Drugs 40, 157–162 (2022). https://doi.org/10.1007/s10637-021-01157-8

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  • DOI: https://doi.org/10.1007/s10637-021-01157-8

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