Pilot study of the combination of EGFR and mTOR inhibitors in recurrent malignant gliomas
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Updated: Aug 7, 2026
Tumor Treating Field Therapy in Combination with Bevacizumab for the Treatment of Recurrent Glioblastoma
Published on: October 27, 2014
L Doherty1, D C Gigas, S Kesari
1Center for Neuro-Oncology, Dana Farber/Brigham and Women's Cancer Center, Boston, MA 02115, USA.
Abstract:
Malignant gliomas are frequently characterized by amplification of the epidermal growth factor receptor (EGFR) and loss of PTEN tumor suppressor gene. Twenty-eight heavily pretreated patients with recurrent malignant gliomas were administered EGFR inhibitors (gefitinib or erlotinib) in combination with the mTOR (mammalian target of rapamycin) inhibitor sirolimus. The regimens were reasonably well tolerated. Nineteen percent of patients experienced a partial response and 50% had stable disease. Six-month progression-free survival for glioblastoma patients was 25%.
Insights
This study combined epidermal growth factor receptor (EGFR) inhibitors with sirolimus in recurrent malignant glioma patients. The combination therapy showed tolerability and clinical benefit, including partial responses and stable disease.
Area of Science:
- Neuro-oncology
- Molecular targeted therapy
- Cancer genetics
Background:
- Malignant gliomas often exhibit epidermal growth factor receptor (EGFR) amplification and PTEN loss.
- These genetic alterations drive tumor growth and resistance to therapy.
- Recurrent gliomas have limited treatment options.
Purpose of the Study:
- To evaluate the safety and efficacy of combining EGFR inhibitors with mTOR inhibitor sirolimus in heavily pretreated patients with recurrent malignant gliomas.
- To assess response rates and progression-free survival in this patient population.
Main Methods:
- Twenty-eight patients with recurrent malignant gliomas received gefitinib or erlotinib plus sirolimus.
- Patients had received prior treatments for their disease.
- Response evaluation included partial response and stable disease criteria.
Main Results:
- The combination regimen was well-tolerated by most patients.
- Nineteen percent of patients achieved a partial response.
- Fifty percent of patients experienced stable disease, with a 6-month progression-free survival of 25% in glioblastoma patients.
Conclusions:
- Combination therapy with EGFR inhibitors and sirolimus demonstrates a tolerable safety profile in recurrent malignant gliomas.
- The regimen shows potential clinical activity, warranting further investigation in this difficult-to-treat patient group.
- Targeting both EGFR and mTOR pathways may offer a viable strategy for managing malignant gliomas.
