Promising Early Results With Single-Agent Erlotinib in Recurrent Glioblastoma Multiforme

CLEVELAND-Interimanalysis of a phase II trial of erlotinib(Tarceva) for single-agent therapy forrecurrent glioblastoma multiformeshowed promising (although not durable)responses in about half of pa-tients, according to Michael A. Vogelbaum,MD, PhD, of the ClevelandClinic Foundation (abstract 1558).The trial enrolled 31 patients withdocumented recurrent or progressiveglioblastoma multiforme who had receivedprevious radiation therapy andcytotoxic chemotherapy. No enzymeinducingantiepileptic agents wereallowed.Patients were treated with 150 mgof erlotinib per day orally until tumorprogression or study withdrawal. Tumorresponse was determined by magneticresonance imaging, and tumortissue samples were analyzed for epidermalgrowth factor receptor (EGFR)amplification.Six Partial ResponsesIn an interim analysis of 27 of 31patients, 6 patients had partial responses.One patient showed a partial responseof his original tumor but thendeveloped a separate unresponsive focus,and five have had disease stabilizationfor more than 3 months. Sixteenpatients had tumor progressionwithin 3 months of starting erlotinib.Six of the 11 patients with eitherpartial response or stable disease laterprogressed and died. Median survivalwas 198.5 days, with a range of 55 to360 days.Median overall survival of the entirecohort was 153 days, and mediantime to progression was 84 days. Themedian time to progression of theresponders was 180 days."The pattern of subsequent treatmentfailure in responders has suggesteda diffuse spread of tumor (eg,gliomatosis cerebri or leptomeningealspread). One patient had a tumorassociatedcyst in which the steadystate erlotinib level was determinedand found to be approximately 40%of that observed in plasma."Approximately one-half of the tumorshave had EGFR amplification,but EGFR amplification has not ensureda response to erlotinib, and responseshave been observed in theabsence of amplification.Encouragedby Responses"Although these results are preliminaryin nature, we are encouragedby the response rate observed to date.The apparent lack of durability ofresponse and the pattern of postresponsefailure may be due, in part,to reduced drug penetration into thebrain, to an inadequate dose, and/orto tumor heterogeneity," Dr. Vogelbaumconcluded.