EGFR Mutation Linked to Deadlier Cases of Gliobastoma

Using targeted therapies in patients with gliobastoma who have the mutation may reduce tumor growth and improve survival outcomes.

New research has linked an epidermal growth factor receptor (EGFR) mutation to worse survival rates in patients with glioblastoma (GBM), according to a recent study.

In the study, which was published in Cancer Cell, the researchers analyzed genetic, clinical, and imaging data from 260 GBM cases at Penn Medicine. Patients with an EGFR mutation, known as A289/T/V, demonstrated increased tumor invasion compared with the rest of the cohort. These patients also had an overall survival rate of 6 months, which is less than the median overall survival of 15 months for patients with GBM.

According to the researchers, EGFR is amplified in nearly 60% of GBM cases and EGFR mutations occur frequently with the disease. Based on a data set of more than 400 patients with GBM, EGFRvIII, which is the most common, was found in 30% of patients and the A289D/T/V mutation was found in approximately 6% of patients.

In the study, the researchers found that the A289V mutation lead to EGFR activation and tumor growth. Mice harboring the A289V mutation had significantly worse survival rates (65%) compared with those with wildtype (non-mutated) EGFR-expressing tumors.

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The researchers administered a monoclonal antibody drug, mAb806, which has been studied in phase 1 and 2 clinical trials for patients with GBM to mutated mice. The drug, which has a high degree of specificity for the A289V mutation, significantly reduced tumor growth and enhanced survival in mice expressing the targeted mutation, as well as mice with the EGFRvIII mutation.

“Glioblastoma is a heterogeneous enough of a disease that I don’t think we will find that 1 single target that will stop all cancer cells from growing,” study author Zev A. Binder, MD, PhD, a senior research investigator in Neurosurgery, said in a press release.

“But showing that we can increase survival in mice by targeting this specific mutation means that we are hitting a significant number of tumor cells and blocking what is really driving their growth.”

According to the researchers, these findings implicate mAb806 as a viable therapeutic option for tumors expressing EGFR mutations, other than EGFRvIII, that should be further investigated. Targeting the mutation may help improve outcomes in patients who harbor the deadly mutations, the researchers concluded.

Reference

Binder ZA, Thorne AH, Bakas S, et al. Epidermal growth factor receptor extracellular domain mutations in glioblastoma present opportunities for clinical imaging and therapeutic development. 2018. Doi: https://doi.org/10.1016/j.ccell.2018.06.006

Penn led Study Finds Mutation Driving Deadlier Brain Tumors and Potential Therapy to Stop It [news release]. Penn Medicine’s website. https://www.pennmedicine.org/news/news-releases/2018/july/penn-led-study-finds-mutation-driving-deadlier-brain-tumors-and-potential-therapy-to-stop-it. Accessed July 10, 2018.