Journal Article

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

Bendszus, Martin, Lee, Eudocia Q, Schiff, David, Dancey, Janet, Lin, Nancy U, Ahluwalia, Manmeet S, Harris, Gordon J, Wefel, Jeffrey S, de Vries, Elisabeth G E, Lassman, Andrew B, Wen, Patrick Y, van den Bent, Martin J, Hodi, F Stephen, Margolin, Kim, Camidge, D Ross, Macdonald, David R, Chang, Susan M, Peereboom, David M, Soffietti, Ricardo

2018

Overview

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.

• Publisher: Elsevier Ltd,Elsevier Limited
• Subject: Antineoplastic Agents - administration & dosage / Antineoplastic Agents - adverse effects / Bias / Blood-brain barrier / Brain cancer / Brain Neoplasms - drug therapy / Brain Neoplasms - mortality / Brain Neoplasms - secondary / Brain tumors / Breast cancer / Cancer therapies / Central nervous system / Clinical trials / Clinical Trials as Topic - methods / Clinical Trials as Topic - standards / Disease / Disease control / Drug development / Drug dosages / Drug therapy / Drugs / Endpoint Determination - standards / Glycoproteins / Hematology, Oncology, and Palliative Medicine / Humans / Immunotherapy / Lung cancer / Melanoma / Metastases / Metastasis / Nervous system / Oncology / Patient Selection / Patients / Radiation therapy / Solid tumors / Toxicity / Treatment Outcome / Tumors / Working groups