Mark Stein, MD
Biomarkers play a key role in the optimization of treatments for patients with prostate cancer. According to Mark Stein, MD, they can even serve as clinical endpoints in trials.
“One thing that investigators have been looking at is if we can use this decrease in circulating tumor cells as a clinical endpoint in a trial,” said Stein. “So, rather than, say, looking at something like survival, do changes in circulating tumor cells correlate so tightly with survival that you can therefore use it as a substitute or surrogate?”
By embedding these biomarkers into clinical studies, he said, trials may be able to move more quickly through development, and answer more lingering questions regarding androgen receptor (AR)–resistance in prostate cancer.
In an interview with OncLive
at the 2016 Chemotherapy Foundation Symposium, Stein, a medical oncologist at Rutgers Cancer Institute of New Jersey, discussed the emergence of circulating biomarkers in clinical practice and how they can be used to combat AR-resistance.
OncLive: Please discuss where we’re at with circulating biomarkers in prostate cancer.
: This is certainly an emerging area in prostate cancer, although we are not routinely using circulating biomarkers in clinical care. With advances in technology, the ability to sample cells, blood, and DNA that is in circulation—these are all going to be integrated into routine care over the coming months and years.
Right now, 1 of the main questions is, when a drug stops working, why does it stop working? Can we figure out who’s going to benefit and who’s not going to benefit? When looking at some of the hormonal therapies, are there predictors of response that we could sample beforehand?
Really, the first use of circulating biomarkers in prostate cancer was just to understand what we call prognostic factors. If somebody has a lot of circulating tumor cells, that is considered a rather poor prognosis factor. Conversely, what’s been shown, if you can decrease the number of circulating tumor cells, patients who respond well seem to do better, and that is an early indicator of having a good response to treatment.
People have looked to see if these markers add anything to traditional markers like CAT scans, or PSA, and they do, which is very exciting. But that’s really focusing mainly on counting the number of cells, and these are papers that go back now about a few years. Some of the new technology is even moving beyond that and looking at specific characteristics of the DNA in circulation.
Are there any specific ongoing trials that are looking to identify biomarkers?
Getting back to this whole idea of counting, and trying to figure out if there’s a decrease in the amount of circulating tumor cells, one important question that needs further validation is this. Typically, the way a trial is done, we follow patients for survival, but that takes a long time. It slows trials down, and it makes it much harder to get answers to our questions.
One thing that investigators have been looking at is if we can use this decrease in circulating tumor cells as a clinical endpoint in a trial. So, rather than, say, looking at something like survival, do changes in circulating tumor cells correlate so tightly with survival that you can therefore use it as a substitute or surrogate?
And so there has been 1 trial that was done that retrospectively showed that it can be used as a surrogate. And now there are going to be additional trials going forward, with circulating tumor cells embedded into the trials, to definitively establish that those changes can be used as a surrogate for overall survival, and therefore expedite trial development.
Another exciting area of development has been using changes in the androgen receptor to understand if tumors will still respond to hormonal therapies. Specifically, drugs like enzalutamide (Xtandi) or abiraterone acetate (Zytiga) have really become routine parts of practice with castration-resistant prostate cancer.
What’s been shown very elegantly now is that the response rate, although perhaps not zero, but close to it, is present when patients have a mutation in the androgen receptor. In other words, cells with a mutation in the androgen receptor don’t respond to hormonal therapy. So that would be an important thing to know right upfront, and it is also potentially an important mechanism of resistance. Therefore, you’d want to go ahead and, for instance, use another form of treatment, such as chemotherapy.