Impact of EGFR^A289T/V mutation on relapse pattern in glioblastoma

Molecular factors influence relapse patterns in glioblastoma. The hotspot mutation located at position 289 of the extracellular domain of the epidermal growth factor receptor (EGFR^A289mut) is associated with a more infiltrative phenotype. The primary objective of this study was to explore the impact of the EGFR^A289 mutation on the pattern of relapse after chemoradiotherapy-based treatment of patients suffering from newly diagnosed glioblastoma.

An ancillary study from a prospective cohort of patients suffering from glioblastoma was conducted. All patients received radiotherapy and concomitant temozolomide. The population was divided into two groups according to EGFR^A289 status (mutated versus wild-type). The primary endpoint was the overlap score (varying from 0 to 1) between the initial irradiated tumor volume (Vinit) and the relapse volume (Vr). Secondary endpoints explored the impact of EGFR^A289mut on survival.

One hundred twenty-eight patients were included and analyzed: 11% had EGFR^A289mut glioblastoma (n = 14/128). EGFR^A289mut glioblastomas had a relapse pattern that was more marginal than EGFR^A289wt glioblastomas: a median overlap score Vinit/Vr of 0.96 was observed in the EGFR^A289mut group versus 1 in the EGFR^A289wt group (P = 0.05). Half of the population with EGFR^A289mut tumor (n = 7/14) had a marginal relapse (i.e. overlap score^Vr/Vinit ≤ 0.95) compared to 23.7% (n = 27/114) in the EGFR^A289wt group, P = 0.035. EGFR^A289mut did not influence survival.

We highlighted a link between the EGFR^A289 mutation and the relapse pattern in glioblastoma. The independent role of EGFR^A289mut and its clinical implication should now be explored in further studies.