ASCO 2023

BIOMEDE study systematizes molecular profiling to guide diagnosis and management in infiltrating brainstem glioma

The BIOlogical MEdicines for Diffuse Intrinsique Pontine Glioma (DIPG) Eradication (BIOMEDE) study, the largest international trial ever conducted in infiltrating brainstem glioma, is changing clinical practice by introducing biopsy at diagnosis as a standard procedure. The study compared three drugs (erlotinib, dasatinib, and everolimus) assigned based on molecular profiling results obtained from the biopsied tumor. Dr. Jacques Grill, pediatric oncologist in the Department of Pediatric and Adolescent Oncology at Gustave Roussy, presented the results in an oral session at the ASCO congress. They decisively demonstrate the feasibility of assigning personalized treatments based on tumor biology and defining robust prognostic markers in these diseases. The study's follow-up team selected everolimus as the reference treatment due to better tolerability and slightly improved median survival for the subsequent study that will test the role of a new molecule, ONC201.

Each year in France, around a hundred children and adults are affected by infiltrating brainstem glioma (DIPG) or a similar tumor located elsewhere in the central nervous system's midline, a group of aggressive brain cancers with a grim prognosis. Surgery is not possible due to the invasive nature of the disease in a critical area of the brain. Only radiotherapy has shown a transient palliative effect on the tumor's progression.

A "practice-changing" study for sequencing at diagnosis

Conducted between 2014 and 2019 by Dr. Jacques Grill, oncologist at Gustave Roussy, the BIOMEDE trial involved 70 centers from 9 European countries, Australia, and New Zealand. Among 279 newly diagnosed DIPG patients, 233 were included in this phase 3 randomized trial, the largest ever conducted worldwide.

Molecular analysis could be performed on 80% of them after a stereotactic biopsy (a procedure performed under general anesthesia to collect a piece of the tumor using a needle). "Historically, DIPGs were rarely biopsied, as the procedure was considered risky, and diagnosis was made based on imaging. With BIOMEDE, for the first time, 100% of patients included in a clinical study for this disease received a molecularly confirmed diagnosis," explains Dr. Jacques Grill. The study also showed that in 10% of cases, the radiological diagnosis was incorrect. "There are tumors of a completely different nature that can radiologically resemble these gliomas but have a different progression and require different management."

New biological and therapeutic insights

BIOMEDE is the first trial to compare three drugs, combined with radiotherapy, in this disease: erlotinib, everolimus, and dasatinib, assigned based on molecular profiling results (biomarkers). With a median follow-up of 5.3 years, the overall median survival, the primary endpoint of the study, was 10.3, 12.1, and 10.5 months for erlotinib, everolimus, and dasatinib, respectively.

"Within a large cohort of patients treated homogeneously, prognostic subgroups could be identified, allowing the identification of patients with specific biology who will benefit from targeted therapeutic approaches in the future," emphasizes Dr. Jacques Grill. "BIOMEDE has provided robust knowledge of DIPG and demonstrated the feasibility of real-time, large-scale molecular profiling at diagnosis to define personalized medicine in this disease." The toxicity profile and the improvement in median overall survival led to the selection of everolimus for the BIOMEDE 2.0 trial, initiated in September 2022, in order to compare it to ONC201, the first drug in a new class of anticancer drugs, considered promising in this disease.

The BIOMEDE 1.0 study was supported by a Clinical Research Hospital Program of the INCa and the associations Imagine For Margo, Etoile de Martin and Friends of Antoine. The deployment of the BIOMEDE 2.0 trial is strongly supported by the "Curing childhood cancer in the 21st century" campaign.

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