Robert Dreicer, MD
Radium-223 dichloride (Xofigo) has proved to be a game-changer in the radiopharmaceutical scene, specifically with the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC), explains Robert Dreicer, MD.
However, even with an encouraging survival benefit in patients with bone-metastatic disease, the agent’s most appropriate use and spot in a sequence with other available agents are still unknown. In an attempt to help answer these questions, ongoing clinical trials are examining the radiopharmaceutical in combinations.
One phase III trial is randomizing patients with bone predominant mCRPC to either radium-223 alone or radium-223 with abiraterone acetate (Zytiga) and prednisone (NCT02043678).
A randomized phase IIa study is investigating the efficacy and safety of radium-223 in combination with abiraterone or enzalutamide (Xtandi) in patients with mCRPC to evaluate bone-scan response, radiological progression-free survival, overall survival, and skeletal events (NCT02034552).
In an interview with OncLive
, Dreicer, associate director for Clinical Research and deputy director of the University of Virginia Cancer Center, discusses the key questions that surround the optimal use and sequencing of radium-223 in patients with mCRPC and how the treatment has altered the field of radiopharmaceuticals.
OncLive: What is the optimal use of radium-223 in the setting of mCRPC?
: Radium-223 is an interesting compound because it is not an androgen receptor (AR)¬–directed therapy and, in prostate cancer, a lot of our therapies are AR-directed. For patients with predominant bone metastases, the drug has been approved prior or posttreatment with docetaxel. For selected patients, it becomes a very useful therapy. What is clear is that the duration of therapy—a 6-month period—a disease that may evolve from an AR perspective is not really being managed by radium-223.
How to integrate the AR-directed therapies with radium-223 are questions that are now being addressed prospectively. This is really one of those therapies that sort of came upon the scene and clearly has activity, but the optimal use is really not yet defined.
What are your thoughts on administering radium-223 in earlier settings of therapy?
When we talk about early, the question is, “Is this a therapy that should be used before AR therapeutics?” I don’t think we know the answer to that. It has clearly been approved for early use, but most patients still wind up getting AR-directed therapy as an initial treatment. Additionally, whether or not radium-223 needs to be integrated into that are questions that are going to be addressed clinically from a research perspective.
How do you envision radium-223 fitting in sequentially, and what research is seeking to answer this?
Radium-223 is not an AR-mediated therapy; the fact that it is a non-AR–targeted therapy has its own advantages. Obviously, there is survival data. This is a therapy that is really bone targeted, so one has to begin to think about how to integrate this optimally.
There are also ongoing trials looking at radium-223 in combination with a number of different AR-targeted therapies and perhaps that will give us more data and help us make judgments. However, right now, it is really unknown in terms of the absolute appropriate place where it should be used sequentially.
In addition to the survival benefit, what are some other advantages patients have with radium-223?
It is relatively well tolerated; it has a little bit of gastrointestinal toxicity. Most patients tolerate it pretty well. For the most part, it seems to be sparing of the bone marrow; therefore, it allows you to use chemotherapy subsequently, and that is a significant advantage. Again, it is not an AR-targeted therapy, which gives you something else in the toolbox to use.
How has the field of radiopharmaceuticals evolved in recent years?
In fairness, it has been relatively disappointing. There are a lot of radiopharmaceuticals that do not impact survival, and the advantage of radium-223 was that it has a survival benefit. It has been sort of modest with one sort of shining example of potential—and that would be radium-223.
As a whole, how is the treatment paradigm for mCRPC evolving?
You throw in 5 new drugs that have ben approved over the last 4 or 5 years, and it is hard to know exactly how to use those therapies. We are sort of probing along as we await clinical trial data to inform us. Therefore, it is a better problem to have than to not have any available drugs; however, it is a challenge when you don’t have all of the evidence you need.