Robert Dreicer, MD
As oncologists await the next major treatment advances in metastatic castration-resistant prostate cancer (mCRPC), the key in the interim is to optimize the available therapies, says Robert Dreicer, MD.
“Right now, we’ve hit a little bit of a time delay in terms of the therapies that have been developed,” said Dreicer. “Clearly, the next wave of therapies are DNA mismatch repair, targeted therapies, but even that is only going to impact a quarter, perhaps, of patients with castration-resistant disease. So it’s really about optimizing the therapies that we have, as we begin to think about new drugs or new combinations that may be able to push us down the road a little bit.”
One available agent that Dreicer said oncologists are still focused on unleashing the full potential of is radium-223. Optimal use of this treatment remains mostly unknown, with current efforts focusing on exploring the agent’s potential in combination regimens.
For example, a phase III trial is randomizing patients with bone predominant mCRPC to radium-223 plus abiraterone acetate (Zytiga) or abiraterone alone (NCT02043678). Additionally, a randomized phase IIa study is evaluating the efficacy and safety of radium-223 in combination with abiraterone or enzalutamide (Xtandi) in patients with mCRPC to investigate bone-scan response, radiological progression-free survival, overall survival, and skeletal events (NCT02034552).
In an interview with OncLive
at the 2016 Chemotherapy Foundation Symposium (CFS), Dreicer, associate director, Clinical Research, deputy director, University of Virginia Cancer Center, discussed ongoing developments in mCRPC, including the latest approaches with radium-223.
OncLive: Please provide an overview of your presentation at the CFS.
: We reviewed the current state of what we know about next-generation antiandrogen therapies. These therapies have been around for a couple of years now, and one of the striking findings that all clinicians deal with is the cross-resistance to both enzalutamide and abiraterone. This is a major clinical dilemma, and we’re sort of in between recognizing multiple different resistance pathways, but not necessarily being able to predict, with any of the assays available—including AR-V7, probably the most well-defined resistance pathway.
So, we’re really left with making clinical judgments about when a patient might go from one drug to another, and that might depend on prior response, clinical setting, or whether the patient is symptomatic. It’s this kind of clinical management paradigm that we’re in, until we can develop predictive biomarkers to really give us data-driven ways to make decisions.
Are there any agents or trials in development seeking to answer these questions?
We were disappointed earlier this year when the trial of galeterone—which was an agent that was hoped to be able to overcome AR-V7 resistance—was stopped prematurely. There are other next-generation compounds in development, and the AR-V7 assay is moving its way to commercialization. I think this is an area that has active research ongoing.