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European Pediatric Sequencing Programs: Screening for Targetable NTRK Gene Fusions

By: Kayci Reyer
Posted: Tuesday, September 7, 2021

According to research presented as correspondence in JCO Precision Oncology, next-generation sequencing of tumors in pediatric patients may be a valuable tool in identifying NTRK alteration–harboring malignancies potentially treatable with NTRK inhibitor therapy. Gilles Vassal, MD, PhD, of the Gustave Roussy Cancer Center, France, and colleagues recommended using this RNA sequencing to identify both NTRK fusions or other targetable gene fusions in light of the efficacy results of NTRK inhibitors such as larotrectinib and entrectinib, which have been approved for use in adults and children in the United States and Europe.

A pair of studies, MAPPYACTS and INFORM, screened a total of 1,790 patients with relapsed, refractory, or very high–risk pediatric cancer. MAPPYACTS included 690 patients between January 2016 and July 2020, and INFORM included 1,100 patients between February 2015 and July 2020. Between them, 41 patients (8 from MAPPYACTS [1.4%]; 33 from INFORM [3.7%]) were found to have an NTRK alteration. The most frequent alterations were NTRK fusion (n = 25), yet fusion partners such as ETV6 (n = 5), TPM3 (n = 3), TPR (n = 2), SPECC1L (n = 2), and TLE4 (n = 2) were also identified. A total of 14 tumors harbored single-nucleotide variants, and 2 had a focal amplification of the NTRK1 genomic locus.

Larotrectinib was administered to 17 patients with an NTRK fusion. However, seven patients with an NTRK alteration received no NTRK inhibitor therapy due to complete tumor resection, stabilization via conventional therapy, lack of drug availability prior to pediatric trial onset, or loss to follow-up.

“The current development of additional pediatric sequencing programs as part of the Innovative Therapies for Children with Cancer strategy will provide an expanded access to targeted agents for children and adolescents across Europe,” concluded the study authors.

Disclosure: For full disclosures of the study authors, visit ascopubs.org.



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