FDA Announces Clinical Trial Endpoints for Approval of Non–Small Cell Lung Cancer Drugs
This week, the U.S. Food and Drug Administration (FDA) released its guidance for industry document Clinical Trial Endpoints for the Approval of Non–Small Cell Lung Cancer Drugs and Biologics, which allows companies to use several types of clinical trial endpoints, including overall survival and progression-free survival, to support drug effectiveness claims in new drug applications. The new document is a companion to Clinical Trial Endpoints for the Approval of Cancer Drugs and Biologics.
Overall Survival Still the Gold Standard
In its new recommendations, the FDA said it considers overall survival to be the standard clinical benefit endpoint that should be used to establish efficacy of a treatment in patients with locally advanced or metastatic non–small cell lung cancer (NSCLC) but that other endpoints can be considered for approval based on the population and risk-benefit profile of a drug.
The FDA said that progression-free survival may be appropriate as the primary endpoint to establish drug efficacy for approval if the trial is designed to demonstrate a large magnitude for the treatment effect as measured by both the hazard ratio and absolute difference in median progression-free survival, and an acceptable risk-benefit profile of the drug is demonstrated. And while planned interim efficacy analyses based on overall survival may be appropriate, said the FDA, interim efficacy analyses of progression-free survival before completion of patient accrual are discouraged, because “early interim efficacy analyses of [progression-free survival] that cross a stopping boundary often overstate the magnitude of the effect.”
According to the guidance document, the FDA recognizes that patient-reported outcome endpoints, such as delay in symptom progression, are important and that better tools are needed to minimize bias and to define what constitutes a benefit. The FDA is reviewing the adequacy of all patient-reported outcome measures based on the principles outlined in another guidance for industry document, Reported Outcome Measures: Use in Medical Product Development to Support Labeling Claims, and encourages the development of well-defined and reliable patient-reported outcome instruments that capture the essential treatment benefit concepts in the targeted patient population.
Although the general principles outlined in the new guidance document may help applicants select clinical trial endpoints for marketing applications, the FDA suggests that applicants meet with the agency before submitting protocols intended to support new drug applications or biologics license applications.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
