FDA Guidance for Using Metastasis-Free Survival as a Prostate Cancer Trial Endpoint
Posted: Thursday, August 12, 2021
The U.S. Food and Drug Administration (FDA) recently finalized its guidance for industry on considerations for metastasis-free survival as an endpoint in clinical trials in nonmetastatic castration-resistance prostate cancer. It is intended to offer recommendations to sponsors about using this endpoint for development programs for drug or biologic products regulated by the FDA.
Comments from the FDA guidance: “Patients with nonmetastatic castration-resistant prostate cancer can have a prolonged disease course following the detection of a rising PSA [prostate-specific antigen] until documentation of distant metastases or death. Such a prolonged assessment period (in which patients may receive multiple therapies) with low death rates may make the use of overall survival impractical as a primary endpoint to support approval of products in this disease setting.” Consequently, such issues were discussed in 2011 at an Oncologic Drugs Advisory Committee, where other endpoints that could be measured earlier in the course of disease, such as metastasis-free survival—defined as the time from randomization to distant radiographic disease or death—may be useful in assessing treatment effects in such patients.
In the FDA guidance, the following topics regarding the use of metastasis-free survival as an endpoint are addressed: general trial design considerations; imaging modalities and assessments; considerations related to the interpretation of trial results; and factors related to analyses of this endpoint.
In closing from the FDA guidance: “The Oncologic Drugs Advisory Committee noted that the transition from nonmetastatic castration-resistant prostate cancer to radiographically detectable metastatic disease (eg, bone or visceral disease) is a clinically relevant event that can be associated with morbidity and the need for additional medical interventions. Conversely, local progression events may be treated with local therapies, may never progress to distant disease, and may not lead to systemic morbidity. A large treatment effect on metastasis-free survival with an acceptable safety profile could demonstrate clinical benefit and support product approval.”