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Molecular profile to guide personalized medicine in adult patients with primary brain tumors: results from the ProfiLER trial

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Abstract

Immunohistochemistry and recent molecular technologies progressively guided access to personalized anti-tumoral therapies. We explored the feasibility, efficacy, and the impact of molecular profiling in patients with advanced brain tumors. This multicentric prospective trial ProfiLER enrolled patients with primary brain tumors, who have been pre-treated with at least one line of anti-cancer treatment, and for whom molecular profiles had been achieved using next-generation sequencing and/or comparative genomic hybridization on fresh or archived samples from tumor, relapse, or biopsies. A molecular tumor board weekly analyzed results and proposed molecular-based recommended therapy (MBRT). From February 2013 to December 2015, we enrolled 141 patients with primary brain tumor and analyzed 105 patients for whom tumor genomic profiles had been achieved. Histology mainly identified glioblastoma (N = 46, 44%), low-grade glioma (N = 26, 25%), high-grade glioma (N = 12, 11%), and atypical and anaplastic meningioma (N = 8, 8%). Forty-three (41%) patients presented at least one actionable molecular alteration. Out of 61 alterations identified, the most frequent alterations occurred in CDKN2A (N = 18), EGFR (N = 12), PDGFRa (N = 8), PTEN (N = 8), CDK4 (N = 7), KIT (N = 6), PIK3CA (N = 5), and MDM2 (N = 3). Sixteen (15%) patients could not be proposed for a MBRT due to early death (N = 5), lack of available clinical trials (N = 9), or inappropriate results (N = 2). Only six (6%) of the 27 (26%) patients for whom a MBRT had been proposed finally initiated MBRT (everolimus (N = 3), erlotinib (N = 1), ruxolitinib (N = 1), and sorafenib (N = 1)), but discontinued treatment for toxicity (N = 4) or clinical progression (N = 2). High-throughput sequencing in patients with brain tumors may be routinely performed, especially when macroscopic surgery samples are available; nevertheless delays should be reduced. Criteria for clinical trial enrollment should be reconsidered in patients with brain tumors, and a panel of genes specifically dedicated to neurologic tumors should be developed to help decision-making in clinical practice.

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Acknowledgements

The authors thank the participating patients, staff at each of the study sites, the MBT members, as well as Sophie Darnis, PhD, employee of the Centre Leon Bérard, for medical editorial assistance with this manuscript.

Funding

This work was supported by Institut National du Cancer (INCa) LYric [DGOS-INCa-4664], Bpifrance Financement abounded by European Community [E8983-PREDICTIV], Agence Nationale de la Recherche (ANR)-LabEx DEvweCAN [10-LABX-0061], European Union [Project EURACAN 739521], la Fondation ARC, Ligue de l’Ain contre le Cancer, and Centre Leon Bérard (no grant number). The funders had no role in study design, data collection, data analysis, data interpretation, or writing of the report.

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Authors and Affiliations

  1. Department of Medical Oncology, Leon Bérard Cancer Centre, 28, rue Laennec, 69373, Lyon, France

    Alice Bonneville-Levard, Didier Frappaz, Olivier Tredan & Jean-Yves Blay

  2. Department of Clinical Research and Innovation, Léon Bérard Cancer Centre, Lyon, France

    Emilie Lavergne, Véronique Corset, Vincent Agrapart, Sylvie Chabaud & David Pérol

  3. Department of Translational Research and Innovation, Léon Bérard Cancer Centre, Lyon, France

    Daniel Pissaloux, Qing Wang & Valery Attignon

  4. Department of Neuro-Oncology, Hospices Civils de Lyon, Lyon, France

    Stéphanie Cartalat, François Ducray, Laure Thomas-Maisonneuve & Jérôme Honnorat

  5. Department of Neuropathology, Hospices Civils de Lyon, Lyon, France

    David Meyronet

  6. Department of Neuro-Oncology, Central Hospital, Nancy, France

    Luc Taillandier & Marie Blonski

  7. Synergie Lyon Cancer, Bio-Informatics Platform, Léon Bérard Cancer Centre, Lyon, France

    Alain Viari, Christian Baudet & Emilie Sohier

  8. Department of BioPathology, Léon Bérard Cancer Centre, Lyon, France

    Sylvie Lantuejoul, Sandrine Paindavoine, Isabelle Treilleux & Christine Rodriguez

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  1. Alice Bonneville-Levard
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Corresponding author

Correspondence to Alice Bonneville-Levard.

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The authors have declared no potential conflicts of interest.

Ethical approval

The study received local approval (Ethics committee of Lyon Sud-Est IV) and was conducted in accordance with the Good Clinical Practice guidelines of the International Conference on Harmonization, and the Declaration of Helsinki, and relevant French and European laws and directives.

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Bonneville-Levard, A., Frappaz, D., Tredan, O. et al. Molecular profile to guide personalized medicine in adult patients with primary brain tumors: results from the ProfiLER trial. Med Oncol 39, 4 (2022). https://doi.org/10.1007/s12032-021-01536-4

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