CTC levels as a surrogate endpoint for clinical trials in mCRPC


A newly published analysis of data from five major clinical trials involving > 6,000 patients has provided us with additional information about circulating tumor cell (CTC) levels as an endpoint for clinical trials.

The US Food & Drug Administration has already approved so-called “CTC conversion” as a surrogate endpoint for clinical effectiveness of drugs being tested for effectiveness in me with metastatic, castration-resistant prostate cancer. What this means is that if a patients CTC level is ≥ 5 CTCs at baseline and then drops to ≤ 4 CTCs at 13 weeks, this is a demonstration of the effectiveness of the drug being tested.

However, the new paper by Heller et al. in the Journal of Clinical Oncology does two things:

  • It endorses earlier data used to justify CTC conversion as a trial endpoint, and
  • It suggests that a change from a non-zero CTC count at baseline to a CTC count of zero at 13 weeks (CTC0) is an even more accurate surrogate endpoint.

Heller et al. actually looked at a total of six different, possible surrogate endpoints based on CTC and PSA data but it was clear that CTC0 and CTC conversion had the highest degree of predictive correlation to overall survival.

Furthermore, while 51 percent of patients in the trials evaluated could have had their progression evaluated using the CTC conversion endpoint, a total of 75 percent of patients in the trials could have had their progression evaluated using the CTC0 endpoint. In their conclusions, the authors state that:

Both are robust and meaningful response end points for early-phase metastatic castration-resistant prostate cancer clinical trials.

This appears to increase the range of options open to the FDA for using CTC levels as surrogate endpoints in the evaluation of effectiveness of new drugs for the treatment of men with mCRPC. It may also have utility in the evaluation of effectiveness of new drugs for the treatment of other forms of advanced prostate cancer, but more data will be needed before this can be determined with accuracy.

4 Responses

  1. How do they identify CTCs in the blood? Picking out 5 cells out of millions in a milliliter of blood does not seem like it would be easy. You’d want some reliable way to validate the process.

  2. A number of different mechanisms can be used to detect CTCs. Which of these is the most accurate, I am not sure, but here is a link to a detailed article on the subject published in 2013.

  3. Is there any benefit in this for someone, like my husband, who was diagnosed in 2012 with Stage IV metastatic prostate cancer and who has had every known treatment available: Xtandi, Zytiga, docetaxel (Taxotere), and cabazitaxel (Jevtana)?

    He is still receiving Lupron every 6 months, but … his PSA has risen for 2 months in a row — up to 30.95.

  4. Dear Ellen:

    You could certainly think about asking the medical oncologist if he knows what your husband’s CTC count is. However, I have to be truthful and tell you that if that hasn’t already been measured in the relatively recent past, it’s probably not worth getting done now outside of the parameters of a clinical trial of some other new drug that is in development for mCRPC.

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