Dataset Information

NTRK Fusions and TRK Inhibitors: Potential Targeted Therapies for Adult Glioblastoma.

ABSTRACT:

Introduction

Glioblastoma multiforme (GBM) is the most common primary central nervous (CNS) system malignancy with a poor prognosis. The standard treatment for GBM is neurosurgical resection, followed by radiochemotherapy and adjuvant temozolomide chemotherapy. Predictive biomarkers, such as methylation of the promoter region of the O6-methylguanine DNA methyltransferase (MGMT) gene, can successfully distinguish subgroups with different prognosis after temozolomide chemotherapy. Based on multiomics studies, epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF), BRAF V600E mutation, neurotrophic tyrosine receptor kinase (NTRK) fusions and other potential therapy targets have been found.

Methods

We have reviewed the preclinical and clinical evidence for NTRK fusions and TRK inhibitors therapy in cancers with NTRK fusions in pan-cancer and gliomas.

Results

Several NTRK1/2/3 fusions have been reported in GBM and preclinical studies have proven that NTRK fusions are potential driver mutations in some high-grade gliomas. Tropomyosin receptor kinase (TRK) inhibitors have shown efficacy as targeted therapies for extracranial tumors with NTRK fusions in recent clinical trials, with potential CNS tolerability and activity. However, whether NTRK gene fusions can affect survival status, the efficacy and resistance of TRK inhibitors in GBMs are lacking high-level evidences.

Conclusions

For GBM patients, NTRK fusions and TRK inhibitors are potential target therapy strategy but remain biological mechanism and clinical significance unclarified. More clinical data and future clinical trials are needed to provide more evidence that supports targeted therapy for GBM with NTRK fusions.

SUBMITTER: Wang Y

PROVIDER: S-EPMC7734330 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Publications

NTRK Fusions and TRK Inhibitors: Potential Targeted Therapies for Adult Glioblastoma.

Wang Yuekun Y Long Piaopiao P Wang Yu Y Ma Wenbin W

Frontiers in oncology 20201130

<h4>Introduction</h4>Glioblastoma multiforme (GBM) is the most common primary central nervous (CNS) system malignancy with a poor prognosis. The standard treatment for GBM is neurosurgical resection, followed by radiochemotherapy and adjuvant temozolomide chemotherapy. Predictive biomarkers, such as methylation of the promoter region of the O6-methylguanine DNA methyltransferase (MGMT) gene, can successfully distinguish subgroups with different prognosis after temozolomide chemotherapy. Based on ...[more]

PMID: 33330081

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Project description:The clinical profiles and outcomes of patients with neurotrophic tropomyosin receptor kinase fusion-positive (NTRK+) solid tumors receiving standard of care other than tropomyosin receptor kinase inhibitor (TRKi) targeted therapy have not been well documented. Here, we describe the clinical characteristics of patients with NTRK+ tumors treated in clinical practice using information from a United States electronic health record-derived clinicogenomic database. We also compared survival outcomes in NTRK+ patients and matched NTRK fusion-negative (NTRK-) patients and investigated the clinical prognostic value of NTRK fusions. NTRK positivity was defined by the presence of a fusion or rearrangement involving NTRK1/2/3, determined using NGS (Foundation Medicine, Inc.). NTRK+ patients (n = 28) were diagnosed with locally advanced/metastatic solid tumors between January 1, 2011 and December 31, 2019 and had received no TRKis (e.g., entrectinib or larotrectinib) during their patient journey. The unselected NTRK-population comprised 24,903 patients, and the matched NTRK-cohort included 280 patients. NTRK+ patients tended to be younger, were more commonly not smokers, and had a shorter time from advanced diagnosis to first NGS report, compared with unselected NTRK-patients; however, these differences were not significant. Median overall survival (OS) from advanced/metastatic diagnosis was 10.2 months (95% CI, 7.2-14.1) for the NTRK+ cohort versus 10.4 months (95% CI, 6.7-14.3) for the matched NTRK-cohort; hazard ratio for death in NTRK+ versus matched NTRK-patients was 1.6 (95% CI, 1.0-2.5; P = 0.05). Genomic co-alterations were rare in the NTRK+ cohort (only two of 28 patients had a co-alteration). Overall, while hazard ratios suggest NTRK fusions may be a negative prognostic factor of survival, there are no significant indications of any favorable impact of NTRK fusions on patient outcomes. TRKis, with their high response rate and good tolerability, are likely to improve outcomes for patients compared with existing standard-of-care treatments.

Dataset Information

NTRK Fusions and TRK Inhibitors: Potential Targeted Therapies for Adult Glioblastoma.

Introduction

Methods

Results

Conclusions

Publications

NTRK Fusions and TRK Inhibitors: Potential Targeted Therapies for Adult Glioblastoma.

Similar Datasets

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