Clinical outcome of biomarker-guided therapies in adult patients with tumors of the nervous system

March 15, 2023

Mirjam Renovanz 1 2 3, Sylvia C Kurz 1 2, Johannes Rieger 1 2, Bianca Walter 1, Hannes Becker 1 2 3, Hanni Hille 1, Paula Bombach 1 2 4, David Rieger 1 2, Lucia Grosse 1 2, Lara Häusser 1 5, Marco Skardelly 1 2, Daniel J Merk 1, Frank Paulsen 2 4 6, Elgin Hoffmann 2 4 6, Cihan Gani 2 4 6 5, Manuela Neumann 2 4 7 5, Rudi Beschorner 2 4 7 5, Olaf Rieß 4 8 9 5, Cristiana Roggia 4 8, Christopher Schroeder 4 8, Stephan Ossowski 4 8, Sorin Armeanu-Ebinger 4 8, Axel Gschwind 4 8, Saskia Biskup 10 9, Martin Schulze 10, Falko Fend 4 11 9 5, Stephan Singer 4 11 9 5, Lars Zender 4 12 9 5, Claudia Lengerke 13 5, Sara Yvonne Brucker 14 5, Tobias Engler 14 5, Andrea Forschner 15 5, Arnulf Stenzl 16 5, Oliver Kohlbacher 4 17 5, Sven Nahnsen 4 18 12 9 5, Gisela Gabernet 18, Sven Fillinger 18, Benjamin Bender 2 4 19, Ulrike Ernemann 2 4 19, Öznur Öner 4, Janina Beha 4, Holly Sundberg Malek 4, Yvonne Möller 4, Kristina Ruhm 4, Marcos Tatagiba 2 4 3, Jens Schittenhelm 2 4 7 5, Michael Bitzer 4 20 9 5, Nisar Malek 4 20 9 5, Daniel Zips 2 4 6 5, Ghazaleh Tabatabai 1 2 4 9 5

Abstract

Background: The clinical utility of molecular profiling and targeted therapies for neuro-oncology patients outside of clinical trials is not established. We aimed at investigating feasibility and clinical utility of molecular profiling and targeted therapy in adult patients with advanced tumors in the nervous system within a prospective observational study.

Methods: molecular tumor board (MTB)@ZPM (NCT03503149) is a prospective observational precision medicine study for patients with advanced tumors. After inclusion of patients, we performed comprehensive molecular profiling, formulated ranked biomarker-guided therapy recommendations based on consensus by the MTB, and collected prospective clinical outcome data.

Results: Here, we present initial data of 661 adult patients with tumors of the nervous system enrolled by December 31, 2021. Of these, 408 patients were presented at the MTB. Molecular-instructed therapy recommendations could be made in 380/408 (93.1%) cases and were prioritized by evidence levels. Therapies were initiated in 86/380 (22.6%) cases until data cutoff. We observed a progression-free survival ratio >1.3 in 31.3% of patients.

Conclusions: Our study supports the clinical utility of biomarker-guided therapies for neuro-oncology patients and indicates clinical benefit in a subset of patients. Our data might inform future clinical trials, translational studies, and even clinical care.

Keywords: MTB@ZPM-001 (NCT03503149); Molecular tumor board; precision medicine; real-world data; targeted therapy.

  1. Department of Neurology and Interdisciplinary Neuro-Oncology, Hertie Institute for Clinical Brain Research, Eberhard Karls University Tübingen, Germany.
  2. Center for Neuro-Oncology, Comprehensive Cancer Center Tübingen-Stuttgart, University Hospital Tübingen, Germany.
  3. Department of Neurosurgery, Eberhard Karls University Tübingen, Germany.
  4. Center for Personalized Medicine Tübingen, Eberhard Karls University Tübingen, Germany.
  5. German Cancer Consortium (DKTK), DKFZ partner site Tübingen, Eberhard Karls University of Tübingen, Germany.
  6. Department of Radiation Oncology, Eberhard Karls University Tübingen, Germany.
  7. Institute of Pathology and Neuropathology, Department of Neuropathology, Eberhard Karls University Tübingen, Germany.
  8. Institute of Medical Genetics and Applied Genomics, Eberhard Karls University Tübingen, Germany.
  9. Cluster of Excellence (EXC 2180) “Image Guided and Functionally Instructed Tumor Therapies”, Eberhard Karls University of Tübingen, Germany.
  10. Center for Genomics and Transcriptomics (CeGaT) & Center for Human Genetics Tübingen, Germany.
  11. Department of Pathology and Neuropathology, Institute of Pathology and Molecular Pathology, Eberhard Karls University Tübingen, Germany.
  12. Department of Medical Oncology and Pneumology (Internal Medicine VIII), Eberhard Karls University Tübingen, Germany.
  13. Department of Internal Medicine II, Eberhard Karls University Tübingen, Germany.
  14. Department of Gynecology and Obstetrics, Eberhard Karls University Tübingen, Germany.
  15. Department of Dermatology and Center for Dermato-Oncology, Eberhard Karls University Tübingen, Germany.
  16. Department of Urology, Eberhard Karls University Tübingen, Germany.
  17. Institute for Translational Bioinformatics, Eberhard Karls University Tübingen, Germany.
  18. Quantitative Biology Center (QBiC), Eberhard Karls University Tübingen, Germany.
  19. Department of Diagnostic and Interventional Neuroradiology, Department of Radiology, Eberhard Karls University Tübingen, Germany.
  20. Department of Internal Medicine I, Eberhard Karls University Tübingen, Germany.