麻豆传媒

Baseline circulating tumor cell (CTC) count was found to be significantly predictive of clinical outcome in a phase III trial of metastatic castration-sensitive prostate cancer (mCSPC) presented at the .

In this exclusive 麻豆传媒 video, lead researcher , of the Keck School of Medicine and Norris Comprehensive Cancer Center at the University of Southern California, explains that the results suggest that CTC count could be used as a noninvasive biomarker to help guide treatment decisions.

Following is a transcript of his remarks:

Hi, my name is Amir Goldkorn. I'm a medical oncologist and an associate professor at University of Southern California Keck School of Medicine. I want to tell you briefly about the results of our study looking at circulating tumor cells, or CTCs, in metastatic castrate-sensitive prostate cancer that we just presented as an oral abstract at the ASCO 2020 meeting.

So currently in metastatic castrate-sensitive prostate cancer, the standard of care for therapy is combination of androgen deprivation therapy, or ADT, usually plus another drug, sometimes abiraterone or enzalutamide or chemotherapy. But we have very few biomarkers to guide the way that we treat patients to tell us who will respond and for how long. The FDA-cleared CELLSEARCH platform has been looked at extensively in metastatic castration-resistant prostate cancer, a more advanced disease state. So we asked them for this study whether we could also use it as a biomarker, the CTC counts, to tell us how patients will respond and for how long in metastatic castrate-sensitive prostate cancer.

We did this in a large phase III clinical trial, SWOG S1216, a study run by the NCI Southwest Oncology Group. The PI on the clinical trials is Neeraj Agarwal of the University of Utah. What we did in our CTC study was we obtained baseline CTC counts for men going on trial. These men, 1,200 men, were randomized to receive ADT with either bicalutamide or orteronel, which is a CYP17 inhibitor in a class like abiraterone. And what we looked at for readouts is a response to hormonal therapy, which we defined as the 7-month PSA. That means after the 6 months of treatment, at month seven, had the PSA fallen to less than 0.2, 0.2-4.0, or >4.0, which has been previously shown to be an intermediate endpoint actually for overall survival as well. And the other thing we looked at is progression, 2-year progression-free survival.

And what we found was actually pretty significant. There was a very big difference between men who had versus did not have CTCs. For example, comparing a man who had zero CTCs at baseline versus a man who had five or more CTCs, the man who had zero CTCs had more than a six-fold odds ratio of having a complete response in terms of a 7-month PSA on hormonal therapy, relative to the man who had five or more CTCs. And conversely, the man who had five or more CTCs had an almost four-fold odds ratio for progression 2 years on therapy relative to the man who had zero CTCs. And these sorts of relationships held across different cut points. We also looked at men with fewer than five versus greater than five, which is a cut point often used in castrate-resistant disease. We also looked at having any CTCs versus no CTCs, and all of these had statistically significant differences.

So, we conclude from this study that baseline CTC counts were indeed highly prognostic of PSA response and progression in this cohort of men with metastatic castrate-sensitive prostate cancer who were just starting their therapy with hormonal treatment. And the implications for this in the clinical setting is that, hopefully even at this stage, it might give us a little bit more information about our patients when they come through the door. For example, if we have a gentleman coming in to begin therapy who is older or more frail, but has zero CTCs, we may feel that he would do quite well with standard hormonal therapies and feel comfortable knowing that he would have favorable outcomes. Versus another gentleman who comes in the door, but maybe has many more CTCs, we may consider him to have a less likely chance of having favorable outcomes with just hormonal therapies. And someone like that we may be more likely to try to use more intensified therapies or even trials of new combination therapies for more aggressive treatment. Ultimately we want to get the final overall survival data from this trial and all the data compiled. We would look at this also to look at CTC counts as a predictive factor, meaning can they help us select between different types of treatments, so we will do that analysis by treatment arm of this trial. And ultimately we may be able to build on this with new trials, where CTC counts could be taken into account to help us predict who will respond and who will not respond to particular treatments such as ADT plus chemo versus abiraterone or enzalutamide. So ultimately we hope that this will tell us not only how patients will do overall, but perhaps be useful to help guide specific choice of treatment.

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