EGFR Amplification/Overexpression Associated With Improved Response of Glioblastoma to Metronomic Temozolomide


Get Permission

In a study reported in Journal of the National Cancer Institute, Cominelli and colleagues found that EGFR amplification/overexpression was associated with improved response of glioblastoma to adjuvant metronomic (every day of a 28 day cycle at a dosing of 50-75 mg/m2) but not standard (5 consecutive days of temozolomide in a 28 day cycle at a dosing of 150-200 mg/m2) temozolomide schedules.

Analysis of a cohort of glioblastoma patients showed no relationship of survival with gene classifiers associated with molecular glioblastoma subtypes in those receiving temozolomide in a standard schedule. However, EGFR amplification/overexpression was associated with significantly better progression-free survival and overall survival (hazard ratio = 0.22, P = .001, for high vs low) in those receiving metronomic treatment. Long-term survival in those receiving metronomic treatment was independent of MGMT and EGFRvIII-mutant status and was more likely in those with EGFR overexpression with PTEN loss.

In studies in vitro, temozolomide-treated EGFR-positive human-derived glioblastoma cancer stem cells exhibited selective dose- and time-dependent reductions in survival, mediated by inhibition of NF-κB (nuclear factor kappa B) transcriptional activity. Analysis of samples from recurrent metronomic-treated ­EGFR-overexpressing patients showed reductions in EGFR-amplified cells and NF-κB/p65 ­expression.

The investigators concluded: ­“EGFR-amplified/overexpressing glioblastomas strongly benefit from metronomic temozolomide-based therapies.” ■

Cominelli M, et al: J Natl Cancer Inst 107:pii: djv041, 2015.

 


Advertisement

Advertisement



;
Advertisement

By continuing to browse this site you permit us and our partners to place identification cookies on your browser and agree to our use of cookies to identify you for marketing. Read our Privacy Policy to learn more.