Validation of blinded events review committee (ERC)-determined time to neurologic progression (TTNP) demonstrates correlation with survival, radiologic progression, and functional independence endpoints

1534 Background: Survival is a standard endpoint for brain metastasis trials, but inadequately measures treatment benefit because of competing risks for death from systemic disease, and does not account for neurologic function, an important quality of life consideration. There is no standardized and validated tool to measure TTNP. The purpose of this study was to test the validity of ERC-determined TTNP. Methods: In a prospective, randomized phase 3 trial of whole brain radiation +/−motexafin gadolinium for patients (pts) with brain metastases, 401 pts underwent standardized neurologic exam, neurocognitive tests (NCT), evaluation of symptoms, functional independence (Barthel Index), and MRI. Using a pre-specified algorithm, the ERC reviewed blinded clinical data, excluding MRI, to score progression if 2 of 3 functional domains (NCT, neuro exam, neuro symptoms) showed progression on consecutive visits (Mehta J Clin Oncol 21:2529, 2003). TTNP was compared to survival, MRI progression, and time to loss of fu...