Entrectinib in Two Pediatric Patients With Inflammatory Myofibroblastic Tumors Harboring ROS1 or ALK Gene Fusions.

Abstract

Inflammatory myofibroblastic tumor (IMT) is a rare, indolent spindle cell tumor that typically affects children and young adults.1,2 IMTs occur predominantly in visceral soft tissue and are categorized as an intermediate malignancy because they have a potential for local recurrence but rarely progress to distant metastases.2,3 Approximately 50% of IMTs harbor ALK rearrangements, although gene fusions involving ROS1, NTRK3, and PDGFRβ have also been identified.2,4–6 Previously, the presence of ALK gene fusions has typically been identified using immunohistochemistry7; however, newer techniques such as hybridization capture-based next-generation sequencing (NGS) and NGS-based anchored multiplex polymerase chain reaction (PCR) testing can now be used to detect gene fusions.8–10 The identification of patients with actionable gene fusions is important given the availability of promising therapeutic strategies.2,4 Surgical resection is the standard of care for patients with solitary IMT,11 but patients with unresectable or advanced disease have limited treatment options. The current National Comprehensive Cancer Network guidelines for soft tissue sarcoma recommend the use of ALK inhibitors for patients with ALK gene fusions12; however, there are no targeted agents approved specifically for use in fusion-positive IMT. Entrectinib is an investigational, central nervous system (CNS)-active, potent, and selective inhibitor of TRK, ROS1, and ALK.8,13,14 In phase 1 trials, entrectinib demonstrated clinical efficacy in patients with different tumor types harboring NTRK, ROS1, or ALK fusions, regardless of the fusion partner gene.8 A majority of the responses to entrectinib occurred in a rapid and durable manner, and some patients remained on study due to clinical benefit even after experiencing disease progression.8 Here, we present 2 patients with fusion-positive IMT (DCTN1-ALK and TFG-ROS1) who were enrolled in the ongoing STARTRK-NG phase 1/1b trial ({type:clinical-trial,attrs:{text:NCT02650401,term_id:NCT02650401}}NCT02650401) and treated with entrectinib. These patients were identified as having targetable gene fusions using 2 diagnostic testing methods, a hybrid capture-based targeted exome sequencing assay and anchored multiplex PCR,15,16 at different stages of a diagnostic testing workflow.