Regulatory Focus™ > News Articles > 2021 > 7 > FDA finalizes guidance on studying CNS metastases in cancer trials

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Posted 06 July 2021 | By Kari Oakes 

FDA finalizes guidance on studying CNS metastases in cancer trials

3280 A final guidance document from the US Food and Drug Association (FDA) provides recommendations for drug developers on how best to evaluate the safety and efficacy of cancer drugs in patients with central nervous system (CNS) metastases. The document finalizes a draft guidance issued in August 2020.
"There are few effective treatments for patients with central nervous system (CNS) metastases – a type of cancer that has spread from the original tumor to the CNS and is associated with a higher risk of death,” said Richard Pazdur, director of FDA’s Oncology Center of Excellence, in a statement issued when the draft guidance was released. At the time, Pazdur also noted that “few clinical trials” test cancer drugs in patients with CNS metastases, despite the fact that many cancers metastasize to the brain or other CNS sites.
“Metastatic cancer is a systemic disease; therefore, evaluation of the effectiveness of cancer drugs includes consideration of whether the cancer is controlled at all disease sites,” notes FDA in the guidance.
The document outlines clinical trials design considerations for trials of systemic anticancer drugs that include patients with CNS metastases in the study population, when the product labeling is expected to include a description of CNS anti-tumor activity. Considerations for the patient population, available therapies, and prior therapies received are addressed in the guidance. Additionally, trial designs should account for prior therapies received and plan for assessment of CNS metastases.
Baseline and periodic magnetic resonance imaging with gadolinium contrast is the preferred modality, and the protocol should apply RECIST 1.1, Response Assessment in Neuro-Oncology – Brain Metastases [RANO-BM], the standard response criteria for evaluation of CNS metastases
Appropriate study endpoints related to CNS metastases are outlined in the guidance, which also reviews how to address leptomeningeal disease, considered by FDA “to be a disease of the entire CNS compartment.”
The final guidance reflects some updates and suggestions received during the comment period on the draft version of the document. (RELATED: FDA drafts recommendations for studying cancer drugs in patients with CNS metastases, Regulatory Focus 26 August 2020)
Among other changes, the final guidance clarifies the number of stratification factors that should be specified in a trial to minimize the risk of bias. Also, the final version makes clear that the duration of both CNS and systemic response to a therapy should be tracked. An additional 6-month timepoint was added in the final version, as was the addition of progression-free survival for patients with brain metastases “when CNS is a common metastatic site,” according to the Federal Register announcement of the availability of the final guidance.
Bristol Myers Squibb and the University of Texas’ MD Anderson Cancer Center were among the groups who submitted comments.


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