Infantile Fibrosarcoma With NTRK3-ETV6 Fusion Successfully Treated With the Tropomyosin-Related Kinase Inhibitor LOXO-101.
Infantile fibrosarcoma (IFS) is a rare pediatric cancer typically presenting in the first 2 years of life. Surgical resection is usually curative and chemotherapy is active against gross residual disease. However, when recurrences occur, therapeutic options are limited. We report a case of refractory IFS with constitutive activation of the tropomyosin-related kinase (TRK) signaling pathway from an ETS variant gene 6-neurotrophin 3 receptor gene (ETV6-NTRK3) gene fusion. The patient enrolled in a pediatric Phase 1 trial of LOXO-101, an experimental, highly selective inhibitor of TRK. The patient experienced a rapid, radiographic response, demonstrating the potential for LOXO-101 to provide benefit for IFS harboring NTRK gene fusions.
Nemours Children's Hospital, Orlando, Florida.
Ramamoorthy
R
Nagasubramanian
Nemours Children's Hospital, Orlando, Florida.
Julie
J
Wei
Nemours Children's Hospital, Orlando, Florida.
Paul
P
Gordon
Department of Otolaryngology - Head and Neck Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
Jeff C
JC
Rastatter
Loxo Oncology Inc, South San Francisco, California.
Michael C
MC
Cox
St. Jude Children's Research Hospital, Memphis, Tennessee.
Alberto
A
Pappo
D005260:Female; D005354:Fibrosarcoma / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000235:genetics* / Q000601:surgery; D006801:Humans; D007223:Infant; D008279:Magnetic Resonance Imaging; D050783:Proto-Oncogene Proteins c-ets / Q000235:genetics*; D011720:Pyrazoles / Q000627:therapeutic use*; D011743:Pyrimidines / Q000627:therapeutic use*; D020812:Receptor, trkC / Q000037:antagonists & inhibitors* / Q000235:genetics*; D011993:Recombinant Fusion Proteins / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics*; D000097764:ETS Translocation Variant 6 Protein
D050783:Proto-Oncogene Proteins c-ets; D011720:Pyrazoles; D011743:Pyrimidines; D020812:Receptor, trkC; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; D000097764:ETS Translocation Variant 6 Protein; C000609083:larotrectinib
ETV6-NTRK3; LOXO-101; gene fusion; infantile fibrosarcoma; tropomyosin-related kinase (TRK)