Oliver Sartor, MD
There have been significant strides in identifying biomarkers to appropriately treat patients with prostate cancer, according to Oliver Sartor, MD. Although defining mutations and subgrouping patients may take longer than anticipated, he adds, the results could be vastly beneficial.
In an interview with OncLive
, Sartor, the medical director of Tulane Cancer Center, discusses current research with biomarkers in prostate cancer, as well as how some treatments may be utilized as both single agents and in combination.
OncLive: How has the role of biomarkers evolved in prostate cancer?
There has been tremendous evolution in the biomarker space, really over the last year and a half. We can begin to look back and ask questions about what we can do in the way of molecular testing that can allow us to predict how therapies might work or not work.
If we look back at what I thought was important initial information was the discovery of ARV7, which was detected originally by the Johns Hopkins Medicine groups as well as some others. They brought it into the clinic to be able to show that ARV7 would be predictive of resistance to either abiraterone (Zytiga) or enzalutamide (Xtandi) and that helped to move things forward. They were able to do that with circulating tumor cells, and that was an important step because you didn't have to put a needle in the tumor.
Then we look at another important advance by the Stand Up To Cancer group and also funded by the Prostate Cancer Foundation. What they did was determine how to put needles directly into tumors and to define a whole series of somatic alterations and mutations that were clinically relevant. It turns out there's a high number of individuals, probably about 25%, who have defects in their DNA repair pathways. Based on a New England Journal of Medicine
article that was published last October, a PARP inhibitor might be able to target that series of individuals who had DNA repair mutations.
More recently, we have begun to show as well as others, that carboplatin may be a particularly good agent within individuals with BRCA2
mutations. There's some unpublished data that we're putting together that would indicate the same. So, we've been moving to try to define DNA repair defects and things that might be able to elicit responses in those patients, and right now preliminarily, the platinums and the potential radiation, which I didn't mention, and PARP inhibitors are areas that need further exploration.
In addition, we've been able to define increasingly the amplification of AR and the utilization and detection of mutations within an androgen receptor that confer resistance. As we begin to look at the field, we have DNA repair defects, we have androgen receptor amplification, we have mutations, and we have variants of androgen receptors; each of these are looking like they might predictive biomarkers. More work is necessary, but it's a rapidly evolving field and one that is very exciting right now.
In the real world, how much testing is being done to identify these sorts of mutations?
The current commercial utility is somewhat limited, because ARV7 tests are limited to laboratories. At Johns Hopkins, there's a clinical trial where they're embedding this test into their trial design, but it's a little bit difficult to simply get the tests done. It is the same with the AR amplification and mutations. Now, there are newer companies that are analyzing circulating free DNA and can give you insights into things like DNA repair defect and mutations, BRAF
mutations, alterations in the androgen receptor, and we're incorporating it into our practice today, but it's still relatively exploratory.
Are there studies that are going to move that forward?
Yes, there are multiple studies that are going to move that forward. There are plans for a study with olaparib (Lynparza) which is a PARP inhibitor. That study is going to be looking prospectively in a multi-institutional manner for those with DNA repair defects. That trial is under design right now. There's also been several companies well known in the prostate cancer field that require PARP inhibitors, and they are going to be developing their own strategies.