CTP-11. Biological Medicines for Diffuse Intrinsic Pontine Gliomas (DIPG) Eradication (BIOMEDE). An International Randomized Phase II Biomarker-driven Platform Trial Comparing Three Targeted Therapies in Combination with Radiotherapy

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Abstract DIPG is the most aggressive brain cancer. Radiotherapy offers transient palliation but survival could not be improved significantly since 50 years. 233 patients with biopsy-confirmed DIPG harboring H3K27me3 loss were randomized to one of the three drugs (erlotinib, everolimus or dasatinib) in addition to radiotherapy. Immunohistochemical biomarkers were assessed centrally together with whole exome and RNA sequencing. Treatment allocation was designed so that a drug could not be randomized if the corresponding biomarker was absent in the tumor. Toxicity was manageable, everolimus showing significantly less adverse events. With a median follow-up of 5.3 years, median OS from the date of treatment start was 9.0, 11.3 and 9.4 months for erlotinib, everolimus and dasatinib, respectively (p=NS). The presence of TP53 mutations frequently associated with numerous structural chromosomal aberrations was the strongest predictor for poor survival (HR of 2.552; 95% CI = 1.476-3.345; p=0.0002). Mutations in the mTOR pathway or its pathway activation on gene expression analysis were associated with a better response to everolimus. Four long-term survivors all treated with everolimus were alive more than six years from diagnosis.

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