Metastasis-free survival as a surrogate endpoint in prostate cancer clinical trials


As many readers will have realized, the major regulatory authorities started, some time ago, to accept prostate cancer progression-free survival of differing types as a surrogate for overall survival in the approval of some drugs for the treatment of prostate cancer. Examples to date have included:

  • The approval of abiraterone acetate (Zytiga) in the treatment of non-metastatic, castration-resistant prostate cancer (nmCRPC)
  • The approval of enzalutamide (Xtandi) in the treatment of nmCRPC

and there are several other drugs in development that are also using these types of endpoint in order to seek approval.

We now also have data from a massive, retrospective data analysis by the ICECaP Working Group (that’s the Intermediate Clinical Endpoints in Cancer of the Prostate Working Group to be exact) showing that metastasis-free survival is a strong surrogate for overall survival among men with localized prostate cancer.

The data behind this finding were first presented in a poster at the annual meeting of ASCO in 2016, but they have now been published by Xie et al. in the Journal of Clinical Oncology. This research was funded by the Prostate Cancer Foundation.

Hopefully, this study will encourage regulatory authorities to see metastasis-free survival as an appropriate endpoint in trials of treatments for localized prostate cancer (since this could cut the time for completion of such trials by several years).

Of course the question of how to define metastasis-free survival is becoming more complicated today. It used to be clear. It meant no sign of any metastasis on a bone scan. Arguably, today, metastasis-free survival means no sign of metastasis on an [11C]choline PET/CT scan or an Axumin PET/CT scan or a gallium-68 PSMA PET scan. However, …

In the 12,712 men enrolled in the 19 major clinical trials who were treated between 1987 and 2011 in the studies evaluated by the ICECaP Working Group, it still meant no sign of metastasis on a bone scan!

2 Responses

  1. Hopefully in these days of BAT it is increasingly a correlation not an equivalence.

  2. This is a complicated topic we discuss at every research trial opportunity at SWOG and ASCO. For advanced case research “overall survival” is almost always the primary end point. But biochemical progression is more frequently used as a secondary endpoint than progression measured by bone or visceral metastasis. Ideally both should be considered as secondary end points.

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