Regression of <i>ETV6-NTRK3</i> Infantile Glioblastoma After First-Line Treatment With Larotrectinib

Alharbi, Musa; Mobark, Nahla Ali; Balbaid, Ali Abdullah O; Alanazi, Fatmah A; Aljabarat, Wael abdel Rahman; Bakhsh, Eman; Ramkissoon, Shakti; Abedalthagafi, Malak

doi:10.1200/po.20.00017

Cited by 19 publications

(17 citation statements)

References 25 publications

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“…Buerki et al reported a case of a 2‐month‐old girl with infantile glioblastoma harboring an in‐frame TPM3 ‐ NTRK1 fusion who had been managed with larotrectinib for 20 months at the time of report, with evidence of tumor shrinkage [25]. Alharbi et al also reported a case of 18‐month‐old with infantile glioblastoma that was found to harbor an ETV6 ‐ NTRK3 fusion and showed significant tumor regression 8 weeks following larotrectinib treatment [26]. One patient with a glioneuronal tumor harboring a BCAN ‐ NTRK1 fusion showed a temporary clinical and radiologic response to entrectinib lasting 11 months before disease progression and treatment discontinuation [23].…”

Section: Molecular Tumor Boardmentioning

confidence: 99%

Mosaicism for Receptor Tyrosine Kinase Activation in a Glioblastoma Involving Both PDGFRA Amplification and NTRK2 Fusion

et al. 2021

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Rearrangements involving the neurotrophic receptor tyrosine kinase (NTRK) gene family have been reported in diverse tumor types, and NTRK-targeted therapies have recently been approved. Here we report a case of a 26-year-old man with an NTRK2-rearranged IDH-wildtype glioblastoma who showed a robust but temporary response to the NTRK inhibitor larotrectinib. Re-biopsy after disease progression showed elimination of the NTRK2-rearranged tumor cell clones, with secondary emergence of a PDGFRAamplified subclone. Retrospective examination of the initial biopsy material confirmed rare cells harboring PDGFRA amplification. While mosaic amplification of multiple receptor tyrosine kinase genes in glioblastoma has been previously described, mosaicism involving a fusion gene driver event has not. This case highlights the potential efficacy of NTRK-targeted treatment in glioblastoma and the implications of molecular heterogeneity in the setting of targeted therapy. Key points.

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Section: Molecular Tumor Boardmentioning

confidence: 99%

Mosaicism for Receptor Tyrosine Kinase Activation in a Glioblastoma Involving Both PDGFRA Amplification and NTRK2 Fusion

et al. 2021

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“…In case of LFS progression, ongoing studies are evaluating the therapeutic efficacy of Larotrectinib for those patients that, unlike our patient, have fusion-transcripts of the NTRK1 gene [ 27 , 28 , 29 ]. The NTRK1 gene encodes a protein-kinase located on the cell surface, in particular on sensory neurons, that phosphorylates specific loci of other proteins, thus modulating their activity in order to regulate cell growth and survival.…”

Section: Discussionmentioning

confidence: 99%

A Unique Case of Bilateral Thalamic High-Grade Glioma in a Pediatric Patient with LI-Fraumeni Syndrome: Case Presentation and Review of the Literature

Messina

Cazzato

Perillo

et al. 2021

Neurology International

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Li-Fraumeni syndrome (LFS) is a rare high-penetrance and autosomal-dominant pathological condition caused by the germline mutation of the TP53 gene, predisposing to the development of tumors from pediatric age. We conducted a qualitative systematic review following the ENTREQ (Enhancing Transparency in Reporting the Synthesis of Qualitative Research) framework. A search was made in MEDLINE/Pubmed and MeSH Database using the terms “Li-Fraumeni” AND “pediatric high-grade glioma (HGG)”, identifying six cases of HGGs in pediatric patients with LFS. We added a further case with peculiar features such as no familiar history of LFS, association of embryonal rhabdomyosarcoma and bithalamic HGG, whose immunohistochemical profile was accurately defined by Next Generation Sequencing. Knowledge synthesis and case analysis grounded the discussion about challenges in the management of this pathology in pediatric age.

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“…Both larotrectinib and entrectinib have been associated with CNS activity, with responses reported in CNS metastases and primary CNS tumors in patients with TRK fusion cancer (46)(47)(48)(49). In the updated larotrectinib pooled analysis, intracranial responses were not a prespecified endpoint.…”

Section: Cns Activitymentioning

confidence: 99%

Tropomyosin Receptor Kinase Inhibitors for the Treatment of TRK Fusion Cancer

Laetsch

Hong

2021

Clinical Cancer Research

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Chromosomal rearrangements of NTRK1-3 resulting in gene fusions (NTRK gene fusions) have been clinically validated as oncogenic drivers in a wide range of human cancers.Typically, NTRK gene fusions involve both inter-and intrachromosomal fusions of the 5′ regions of a variety of genes with the 3′ regions of NTRK genes leading to TRK fusion proteins with constitutive, ligand-independent activation of the intrinsic tyrosine kinase. The incidence of NTRK gene fusions can range from the majority of cases in certain rare cancers to lower rates in a wide range of more common cancers. Two small molecule TRK inhibitors have recently received regulatory approval for the treatment of patients with solid tumors harboring NTRK gene fusions, including the selective TRK inhibitor, larotrectinib and the TRK/ROS1/ALK multikinase inhibitor, entrectinib. In this review we consider the practicalities of detecting tumors harboring NTRK gene fusions, the pharmacologic properties of TRK inhibitors currently in clinical development, the clinical evidence for larotrectinib and entrectinib efficacy, and possible resistance mechanisms.Research.

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Regression of ETV6-NTRK3 Infantile Glioblastoma After First-Line Treatment With Larotrectinib

Cited by 19 publications

References 25 publications

Mosaicism for Receptor Tyrosine Kinase Activation in a Glioblastoma Involving Both PDGFRA Amplification and NTRK2 Fusion

Mosaicism for Receptor Tyrosine Kinase Activation in a Glioblastoma Involving Both PDGFRA Amplification and NTRK2 Fusion

A Unique Case of Bilateral Thalamic High-Grade Glioma in a Pediatric Patient with LI-Fraumeni Syndrome: Case Presentation and Review of the Literature

Tropomyosin Receptor Kinase Inhibitors for the Treatment of TRK Fusion Cancer

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