Erlotinib HCL for glioblastoma multiforme in first relapse, a phase II trial.
1555 Background: Erlotinib HCL (Tarceva), an orally active, highly potent and selective inhibitor of the epidermal growth factor receptor (HER1/EGFR), has documented clinical activity in glioblastoma multiforme (GBM) (M Prados ASCO 02). GBM is an interesting target for EGFR inhibitors because of the high rate of EGFR gene amplification and activating mutations in EGFR (i.e. EGFRvIII). METHODS: A multi-institutional phase II clinical trial of the single agent Tarceva was initiated in August 2003 for GBM patients with measurable disease in first relapse. Tarceva is metabolized by CYP3A4, therefore to ensure adequate exposure patients receiving enzyme-inducing anti-epileptic drugs (EIAED group) receive a higher starting dose (300mg/d), otherwise standard dose of 150mg/d was given (non-EIAED group) Individual dose titration until dose-limiting toxicity (diarrhea, rash, other) was allowed, from 150 to 200mg (non-EIAED group) or from 300 to 500mg in 50-mg increments (EIAED group). RESULTS: Forty-eight subjects (19 female, 29 male) with a median age of 50 years (37-70) have been enrolled to date. 21 on concurrent EIAEDs; 27 received 150mg/d initially. 23 of the 48 subjects have been able to dose escalate at least once, 2 are now receiving 450 or 500mg, and 1 discontinued therapy on day 10 due to skin toxicity at their 300mg/d starting dose. Pharmacokinetic measurements are being obtained in this study. At week 8, 1 subject had a CR, 1 subject achieved PR (unconfirmed), 11 had stable disease (SD) although 4 of the SD subjects have subsequently progressed. To date, 27 patients have progressed and 1 is not evaluable. Gene amplification, as determined by FISH, has been seen in 16 of 30 subjects. CONCLUSIONS: These preliminary data suggest that erlotinib is active in recurrent GBM. Updated results, including the association between EGFR status, including gene amplification status, IHC expression, and EGFRvIII status, will be presented. [Table: see text].
Yung, A; Vredenburgh, J; Cloughesy, T; Klencke, BJ; Mischel, PS; Bigner, DD; Aldape, K; Vanderburg, S; Prados, M; Accelerate Brain Cancer Cure Group,
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