Epithelial Growth Factor Receptor inhibitors for treatment of recurrent or progressive high grade glioma: an exploratory study

Abstract

Erlotinib and Gefitinib (EGFRi) are small molecules specifically inhibiting epidermal growth factor receptor (EGFR). We present here data of an exploratory study evaluating EGFRi monotherapy in patients with recurrent or progressive malignant glioma. 21 patients with recurrent or progressive malignant glioma were included in this study. EGFRi treatment was started at a median of 1.8 years (range 0.54 to 10.95) after initial surgery. 20/21 patients had undergone radiotherapy and all patients had received at least one (range 1 to 5, median 2) line of systemic antineoplastic therapy. Patients received 100 or 150 mg Erlotinib or 250 mg Gefitinib orally per day. Median age at primary diagnosis was 47.9 years (range 31.9 to 76 years). 18 patients received a total of 92.8 months (median 3.03) of Erlotinib treatment and 3 patients received a total of 16.1 months (median 6.06) of Gefitinib treatment. The best responses were partial remission in one patient receiving Erlotinib and in two patients receiving Gefitinib, respectively. Median time to progression was 3.05 months. Six months after start of EGFRi treatment, 4/21 (19%) patients were progression-free and 6/21(29%) patients were alive. Expression of EGFRwt, EGFRvIII, PTEN, phospho-Akt or EGFRvIII/PTEN co-expression in tumor cells did not significantly associate with time to progression or survival time. In one patient EGFRi administration had to be discontinued due to toxicity (grade 3 rash). EGFRi monotherapy is associated with therapeutic efficacy in only a small fraction of patients with malignant gliomas. Biomarkers reliably predicting tumor response to EGFRi need to be identified.