EPN-33: FEASIBILITY AND TOLERABILITY OF INTRAVENOUS AND INTRAVENTRICULAR TRASTUZUMAB IN HER2-POSITIVE RECURRENT METASTATIC EPENDYMOMA

BACKGROUND: Recurrent ependymoma continues to be a predominantly incurable disease. Many ependymomas are known to over-express HER2 on the tumor cell surface. The monoclonal antibody trastuzumab interferes with HER2 expression/signaling, although reportedly with poor penetration of the blood-brain barrier following intra-venous administration; however, intraventricularly administered trastuzumab has shown activity in leptomeningeal breast cancer. METHODS: We report on an 11-years-old male with multiply recurrent and intracranially metastatic posterior fossa anaplastic ependymoma, with repeated tumor resections, photon (focal and later craniospinal) and gamma knife radiotherapy, and conventional chemotherapy. He has completed thirteen 21-day cycles of intravenous (every 21 days) and bi-weekly intraventricular trastuzumab, concomitant with 10 days oral and intraventricular etoposide (3 days per week x 2 weeks) over a ten month period. GM-CSF is administered for 5 days prior to each intravenous trastuzumab for immune cell priming. RESULTS: Tumor tissue was found to express both HER2 protein using immunohistochemistry (CB11 antibody; Grade: 75-100%, Intensity: 3+) and chromosome + 1q gain. Fresh frozen metastatic tumor tissue obtained 48 hours following trastuzumab (intra-ventricular and intravenous infusion) confirmed trastuzumab within the tumor by mass spectroscopic analysis. The patient's only toxicity was a single episode of grade 2 leukopenia. There have been no hospitalizations, no transfusion requirements and no infections. He has been attending school full-time. CONCLUSIONS: This regimen has been well-tolerated with no grades III-IV toxicities affording the patient and family a superior quality of life. More long term follow-up is required to assess for efficacy of treatment.