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Published on: October 27, 2014
Epithelial Growth Factor Receptor Inhibitors for treatment of recurrent or progressive high grade glioma: an
M Preusser1, E Gelpi, A Rottenfusser
1Department of Internal Medicine 1, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria.
Introduction:
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.
Patients:
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.
Results:
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).
Conclusion:
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.
Insights
Erlotinib and Gefitinib (EGFRi) showed limited efficacy as monotherapy for malignant glioma patients. Further research is needed to identify biomarkers that predict response to EGFR inhibitors.
Area of Science:
- Neuro-oncology
- Molecular targeted therapy
- Cancer research
Background:
- Epidermal growth factor receptor inhibitors (EGFRi) like Erlotinib and Gefitinib are small molecules targeting EGFR.
- Malignant gliomas are aggressive brain tumors with limited treatment options.
Purpose of the Study:
- To evaluate the efficacy of EGFRi monotherapy in patients with recurrent or progressive malignant glioma.
- To explore potential biomarkers associated with treatment response.
Main Methods:
- An exploratory study included 21 patients with recurrent/progressive malignant glioma.
- Patients received Erlotinib or Gefitinib monotherapy after prior treatments including radiotherapy.
- Treatment duration and patient outcomes were recorded.
Main Results:
- Partial remission was observed in 3 patients (1 Erlotinib, 2 Gefitinib).
- Median time to progression was 3.05 months; 19% were progression-free at 6 months.
- No significant association was found between EGFR pathway markers and clinical outcomes.
Conclusions:
- EGFRi monotherapy demonstrates limited therapeutic efficacy in a small subset of malignant glioma patients.
- Identification of reliable predictive biomarkers for EGFRi response is crucial for clinical application.
