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Lancet Oncol. 2018 Jan;19(1):e20-e32. doi: 10.1016/S1470-2045(17)30693-9.

Clinical trial design for systemic agents in patients with brain metastases from solid tumours: a guideline by the Response Assessment in Neuro-Oncology Brain Metastases working group.

Author information

1
Anschutz Medical Campus, University of Colorado, Aurora, CO, USA. Electronic address: ross.camidge@ucdenver.edu.
2
Center for Neuro-Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
3
Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
4
Department of Medical Oncology, City of Hope National Medical Center, Duarte, CA, USA.
5
Rose Ella Burkhardt Brain Tumor and Neuro-Oncology Center, Solid Tumor Oncology, Cleveland Clinic, Cleveland, OH, USA.
6
Department of Neuroradiology, University of Heidelberg, Heidelberg, Germany.
7
Department of Neurosurgery, University of California, San Francisco, San Francisco, CA, USA.
8
Department of Oncology, Queen's University, Kingston, ON, Canada.
9
Department of Medical Oncology, University Medical Center Groningen, University of Groningen, Netherlands.
10
Department of Radiology, 3D Imaging Lab, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
11
Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA; Department of Medicine, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
12
Department of Neurology and Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, Columbia University, NY, USA.
13
Department of Oncology and Department of Clinical Neurological Sciences, Schulich School of Medicine and Dentistry, Western University, London, ON, Canada.
14
Division of Neuro-Oncology, University of Virginia, Charlottesville, VA, USA.
15
Department of Neurology/Neuro-Oncology, University of Turin, Turin, Italy.
16
Brain Tumor Institute, Erasmus University Medical Center, Rotterdam, Netherlands.
17
Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Abstract

Patients with active CNS disease are often excluded from clinical trials, and data regarding the CNS efficacy of systemic agents are usually obtained late in the drug development process or not at all. In this guideline from the Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) working group, we provide detailed recommendations on when patients with brain metastases from solid tumours should be included or excluded in clinical trials of systemic agents. We also discuss the limitations of retrospective studies in determining the CNS efficacy of systemic drugs. Inclusion of patients with brain metastases early on in the clinical development of a drug or a regimen is needed to generate appropriate CNS efficacy or non-efficacy signals. We consider how to optimally incorporate or exclude such patients in systemic therapy trials depending on the likelihood of CNS activity of the agent by considering three scenarios: drugs that are considered very unlikely to have CNS antitumour activity or efficacy; drugs that are considered very likely to have CNS activity or efficacy; and drugs with minimal baseline information on CNS activity or efficacy. We also address trial design issues unique to patients with brain metastases, including the selection of appropriate CNS endpoints in systemic therapy trials.

PMID:
29304358
DOI:
10.1016/S1470-2045(17)30693-9
[Indexed for MEDLINE]

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