Everolimus Shows Promise in Biomarker-Guided Trial for Diffuse Intrinsic Pontine Glioma Despite Primary Endpoint Not Being Met

A recent phase 2 clinical trial evaluating targeted therapies combined with radiotherapy for diffuse intrinsic pontine glioma (DIPG) found no improvement in overall survival compared to historical controls, but identified biological markers associated with better outcomes and highlighted everolimus as having a more favorable side effect profile.

The BIOMEDE trial, a biomarker-driven, randomized phase 2 study, enrolled 233 children with newly diagnosed, biopsy-proven DIPG to test three targeted agents—erlotinib, everolimus, and dasatinib—each paired with radiotherapy. Treatment assignment was based on tumor biomarker status: patients received erlotinib if their tumors showed epidermal growth factor receptor (EGFR) overexpression, everolimus if they had phosphatase and tensin homolog (PTEN) loss, and dasatinib regardless of biomarker status due to its multitargeted activity. A total of 36 patients received erlotinib, 102 received dasatinib, and 95 received everolimus.

Overall survival from biopsy was the primary endpoint. The median overall survival in the historical control cohort, which had received temozolomide-based therapy prior to biopsy, was 10.8 months (95% confidence interval: 9.5–13.0 months). In the treatment arms, median overall survival was 9.7 months (95% CI: 7.8–14.6) for erlotinib, 9.9 months (95% CI: 8.8–11.2) for dasatinib, and 11.9 months (95% CI: 10.7–14.2) for everolimus. None of the experimental arms showed a statistically significant improvement in overall survival over the control group, leading the independent data monitoring committee to recommend halting the trial for futility.