Targeting NTRK Gene Fusions in Gliomas
Posted: Wednesday, September 29, 2021
According to Roberta Rudá, MD, of the University and City of Health and Science, Turin, Italy, and colleagues, the identification of actionable molecular targets is essential for the treatment of adults and children with rare brain tumors. A review article, which was published in the International Journal of Molecular Sciences, focused on initial experiences in targeting NTRK gene fusions in gliomas.
NTRK gene fusions may be found in up to 40% of cases of non-brainstem high-grade gliomas in pediatric patients younger than age 3. These alterations have also been observed in approximately 15% of pilocytic astrocytomas. In diffuse lower-grade gliomas, as well as in glioblastoma and diffuse intrinsic pontine gliomas, NTRK gene fusions are usually found in less than 2% of cases; according to the investigators, they were not observed in ependymomas or medulloblastomas.
The efficacy of entrectinib, the first developed anti-NTRK gene fusion agent, has been assessed in phase I and II trials for the treatment of primary and secondary brain tumors. According to the investigators, results with this agent in these trials have been “promising.” Furthermore, in a series of pediatric high-grade gliomas, all four patients achieved a radiologic response, including a complete response, when treated with entrectinib.
Larotrectinib is highly specific for NTRK gene fusions; it has been evaluated in pediatric patients with solid tumors, as well as in primary and secondary brain tumors. In two clinical trials, disease control was achieved by all nine patients with primary brain tumors; one patient achieved a partial response after treatment with larotrectinib, whereas the other patients experienced stable disease.
“A second-generation of NTRK inhibitors, including repotrectinib-TPX-0005 and LOXO-195-BAY2731954, are being explored in clinical trials in order to compare their efficacy with first-generation drugs and, more importantly, to tackle tumor resistance to first-line compounds,” the investigators explained.
Disclosure: The study authors reported no conflicts of interest.