Infantile Fibrosarcoma With NTRK3-ETV6 Fusion Successfully Treated With the Tropomyosin-Related Kinase Inhibitor LOXO-101

Abstract

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.

Keywords: ETV6-NTRK3; LOXO-101; gene fusion; infantile fibrosarcoma; tropomyosin-related kinase (TRK).

Figure 1

Magnetic resonance imaging (MRI) of baseline disease assessment of the (A) neck and (B) oral cavity, with areas of interested highlighted with red arrows. Magnetic resonance imaging demonstrating >90% reduction in tumor masses of the (C) neck and (D) oral cavity following completion of the first month of therapy. Confirmation of the tumor response and decreased enhancement demonstrated by MRI of the (E) neck and (F) oral cavity following the second month of therapy.