EPT-18A FEASIBILITY TRIAL OF RAPID TARGETED THERAPY SELECTION FOR CHILDREN WITH RECURRENT MALIGNANT BRAIN TUMORS

Abstract

BACKGROUND: There is no standard therapy for malignant pediatric brain tumors at relapse. We conducted a prospective clinical trial to evaluate the feasibility of rapid selection of targeted therapy using immunohistochemistry (IHC). METHODS: Eligibility criteria included age <30 with recurrent brain tumor confirmed by imaging or pathology. Treatment was recommended to be palliative oral therapy of Temozolomide and Etoposide with the addition of selected oral kinase-inhibitor therapy consisting of either Erlotinib, Dasatinib, Everolimus or Sorafenib. Selection was based on an algorithm using IHC evaluation of a laboratory-developed 6-protein panel deemed by the FDA to be a non-significant risk medical device. Correlative next-generation targeted gene sequencing was performed to further evaluate for driver mutations. RESULTS: Kinase inhibitor selection was completed within the 2 week feasibility timeframe for 15/17 subjects, in a median of 12 days (range 6-23) from time of consent for study participation. Tumor histology included recurrent medulloblastoma(4), ependymoma(4), anaplastic astrocytoma(3), glioblastoma multiforme(3), PNET(2) and chordoma(1). IHC detected HER2 in 1/17, EGFR in 3/17, CKIT in 5/17, PDGFRA in 12/17. PS6 and ERK were detected in all tumors. 6/17 subjects (35%) initiated therapy based on IHC results. Targeted sequencing identified driver mutations in 10/14 tumors, 5 of which confirmed alterations in genes or pathways previously identified by IHC. CONCLUSIONS: It was feasible to rapidly identify therapeutic protein targets in the majority of recurrent pediatric brain tumors using a focused IHC panel.