Lessons learned from drug trials in neurofibromatosis: A systematic review

Britt A.E. Dhaenens, Rosalie E. Ferner, D. Gareth Evans, Guenter Heimann, Cornelia Potratz, Edwin van de Ketterij, Angela M. Kaindl, Geesje Hissink, Charlotte Carton, Annette Bakker, Marco Nievo, Eric Legius, Rianne Oostenbrink*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

2 Citations (Scopus)

Abstract

Neurofibromatosis (NF) is the umbrella term for neurofibromatosis type 1 (NF1), neurofibromatosis type 2 (NF2) and schwannomatosis (SWN). EU-PEARL aims to create a framework for platform trials in NF. The aim of this systematic review is to create an overview of recent clinical drug trials in NF, to identify learning points to guide development of the framework. We searched Embase, Medline and Cochrane register of trials on October 1, 2020 for publications of clinical drug trials in NF patients. We excluded publications published before 2010, systematic reviews, secondary analyses and studies with <10 patients. Data was extracted on manifestations studied, study design, phase, number of participating centres and population size. Full-text review resulted in 42 articles: 31 for NF1, 11 for NF2, none for SWN. Most NF1 trials focused on plexiform neurofibromas (32%). Trials in NF2 solely studied vestibular schwannomas. In NF1, single-arm trials (58%) were most common, and the majority was phase II (74%). For NF2 most trials were single-arm (55%) and exclusively phase II. For both diseases, trials were predominantly single-country and included five centres or less. Study population sizes were small, with the majority including ≤50 patients (74%). In conclusion, NF research is dominated by studies on a limited number out of the wide range of manifestations. We need more trials for cutaneous manifestations and high-grade gliomas in NF1, manifestations other than vestibular schwannoma in NF2 and trials for SWN. Drug development in NF may profit from innovative trials on multiple interventions and increased international collaboration.

Original languageEnglish
Article number104281
JournalEuropean Journal of Medical Genetics
Volume64
Issue number9
DOIs
Publication statusPublished - Aug 2021

Bibliographical note

Funding Information:
The authors are member of the EU Patient-centric clinical trial platform (EU-PEARL). EU-PEARL has received funding from the Innovative Medicines Initiative under grant agreement No 853966. This Joint Undertaking receives support from the European Union's Horizon 2020 research and innovation program and EFPIA and Children's Tumor Foundation, Global Alliance for TB Drug Development non-profit organization, Springworks Therapeutics Inc. This publication reflects the authors' views. Neither IMI nor the European Union, EFPIA, or any Associated Partners are responsible for any use that may be made of the information contained herein.The authors wish to thank Wichor Bramer, Maarten Engel and Elise Krabbendam from the Erasmus MC Medical Library for developing and updating the search strategies. The authors are member of the EU Patient-centric clinical trial platform (EU-PEARL). EU-PEARL has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 853966. This Joint Undertaking receives support from the European Union's Horizon 2020 research and innovation program and EFPIA and Children's Tumor Foundation, Global Alliance for TB Drug Development non-profit organization, Springworks Therapeutics Inc. This publication reflects the authors' views. Neither IMI nor the European Union, EFPIA, or any Associated Partners are responsible for any use that may be made of the information contained herein. Author DGE is supported by the National Institute for Health Research (NIHR) BRCManchester (Grant Reference Number 1215?200074). The funding sources were not involved in the study design, data collection and writing of this review. This research is supported (not financially) by the European Reference Network on Genetic Tumour Risk Syndromes (ERN GENTURIS)?Project ID No 739547. ERN GENTURIS is partly co-funded by the European Union within the framework of the Third Health Programme ?ERN-2016?Framework Partnership Agreement 2017?2021.

Funding Information:
The authors are member of the EU Patient-centric clinical trial platform (EU-PEARL). EU-PEARL has received funding from the Innovative Medicines Initiative under grant agreement No 853966 . This Joint Undertaking receives support from the European Union's Horizon 2020 research and innovation program and EFPIA and Children's Tumor Foundation, Global Alliance for TB Drug Development non-profit organization, Springworks Therapeutics Inc. This publication reflects the authors' views. Neither IMI nor the European Union, EFPIA, or any Associated Partners are responsible for any use that may be made of the information contained herein.

Funding Information:
The authors are member of the EU Patient-centric clinical trial platform (EU-PEARL). EU-PEARL has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 853966 . This Joint Undertaking receives support from the European Union's Horizon 2020 research and innovation program and EFPIA and Children's Tumor Foundation , Global Alliance for TB Drug Development non-profit organization , Springworks Therapeutics Inc . This publication reflects the authors' views. Neither IMI nor the European Union, EFPIA, or any Associated Partners are responsible for any use that may be made of the information contained herein. Author DGE is supported by the National Institute for Health Research (NIHR) BRCManchester (Grant Reference Number 1215–200074 ).

Funding Information:
This research is supported (not financially) by the European Reference Network on Genetic Tumour Risk Syndromes (ERN GENTURIS)—Project ID No 739547. ERN GENTURIS is partly co-funded by the European Union within the framework of the Third Health Programme “ERN-2016—Framework Partnership Agreement 2017–2021.

Publisher Copyright:
© 2021 The Authors

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