2005 Background: In 40–50% of GBM epidermal growth factor receptor (EGFR) is amplified, and often constitutively activated (EGFRvIII mutant). EGFR is therefore a potential therapeutic target. Previous studies suggested activity of EGFR tyrosine-kinase inhibitors in recurrent GBM, particularly in specific molecular subsets. This study explored erlotinib (E) activity in recurrent GBM. Methods: Randomized phase II trial. Eligibility criteria: histologically proven GBM, recurrent >3 months after radiotherapy, Karnofsky performance status (KPS) =70, no prior chemotherapy for recurrent disease, tissue sample for EGFR studies. Patients (pts) received E 150mg/day (300mg/day if on enzyme inducing anti-epileptic drugs [EIAEDs]), or control (TMZ 150–200mg/m2, day 1–5 q4wk or BCNU 60–80mg/m2 i.v., day 1–3 q8wk). If no significant toxicity, E was escalated to 200mg (500mg in patients on EIAEDs). The primary endpoint was 6 months’ PFS in =10/50 pts on E (20%); P0 was set at 15%, and P1 at 30%. Response was assessed wit...