US FDA approves First Oral TRK inhibitor Larotrectinib for cancers in children and adults

Reepa Agrawal
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US FDA approves First Oral TRK inhibitor Larotrectinib for cancers in children and adults 12 Jan, 2019

Larotrectinib (Vitrakvi), a new drug for treatment of tumors having NTRK (neurotrophic receptor tyrosine kinase) gene fusions has been approved by US FDA. The significance of gene fusions in oncogenesis is well established now. Gene fusions arise from genomic rearrangements like translocation, duplication, deletion and chromosomal inversions. The oncogenic fusions also includes altered transcription and constitutive kinase activation. The NTRK gene fusions can be translated into some cancer driving proteins. The oral NTRK inhibitor, Larotrectinib can inhibit these proteins. NTRK gene fusions can be detected by NGS (next generation sequencing) and FISH (fluorescent in situ hybridization).

Although TRK fusions are rare but are found in many different tumors including lung tumors, thyroid tumors, melanoma, gastrointestinal system, soft tissue sarcoma, infantile fibrosarcoma, salivary gland and colonic tumors. In a nutshell for the first time a drug is there against this particular genomic rearrangement, irrespective of the cancer type. Also this can be used in pediatric and adult patients.

This drug is available as liquid formulation as well as oral capsules. The US FDA approval comes after the pooled data released of Phase 1 adult trial, Phase 2 NAVIGATE trial and Phase 1/2 pediatric SCOUT trial. Vitrakvi showed overall response rate of 75% (22% complete response and 53% partial response) across various solid tumors in adults and children. The common adverse effects include raised liver transaminases, anemia, nausea, fatigue, dizziness, vomiting, constipation and diarrhea.



Source : US FDA, Loxo oncology
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