Phase I study of afatinib and radiotherapy (RT) with or without temozolomide (TMZ) in newly diagnosed glioblastoma (GB).

2036Background: GB is a malignant primary incurable CNS tumor with poor prognosis. RT + TMZ is standard treatment for newly diagnosed GB suitable for radical treatment. ErbB pathway dysregulation has a role in the pathogenesis of GB and EGFR activation contributes to RT resistance. The irreversible ErbB family blocker afatinib has a manageable safety profile and modest activity in recurrent GB. This Phase I study assessed the feasibility of first-line afatinib + RT ± TMZ in GB. Methods: This 3+3 dose-escalation study enrolled 36 pts with newly diagnosed GB. Treatment was stratified by MGMT promoter methylation status. Pts with promoter methylation received RT + TMZ + afatinib (20, 30, 40 mg/day) for 6 wks (RT period), then afatinib 40 mg/day + TMZ for up to 6 months before afatinib 40 mg/day until progression/undue AEs (maintenance period; Regimen M). As TMZ has limited benefit in pts with unmethylated MGMT, these pts received RT + afatinib then afatinib (Regimen U). Primary endpoint: MTD of afatinib + RT...