Insights From: Evan Yu, MD, University of Washington; Ulka Vaishampayan, MD, Barbara Ann Karmanos Cancer Institute ; Neeraj Agarwal, MD, Huntsman Cancer Institute
Neeraj Agarwal, MD: Skeletal-related events, such as bone fractures and bone pain, are the most common cause of suffering and death in patients with metastatic castrate-resistant prostate cancer. Early recognition of bone metastasis is very important. A timely start of bone-targeting agents is also very important. Radium-223 is a bone-targeting agent that is also associated with overall survival benefit and is approved for patients who have progressive metastatic castrate-resistant prostate cancer, regardless of whether they have used chemotherapy in the past, could not tolerate chemotherapy, or have refused chemotherapy. They are all eligible for treatment with radium-223.
Based on the recent data from the ERA 223 trial, we cannot recommend use of radium-223 in combination with abiraterone. However, regarding combining radium-223 with enzalutamide, we do not have any data against it. There is an ongoing trial, the PEACE III trial, which is investigating this combination of enzalutamide with radium-223 against enzalutamide alone. Time will tell how good the combination is from an efficacy perspective. However, based on the current data and our own phase II trial results, the combination of enzalutamide and radium-223 seems to be very safe.
Ulka Vaishampayan, MD: The treatment landscape of metastatic prostate cancer, or even nonmetastatic relapsed prostate cancer, is changing very rapidly. A lot of the treatments that we’ve been using so far in the metastatic castrate-resistance space are being moved to earlier settings. Chances are when the patient turns castrate-resistant with metastatic disease, they will potentially have seen a couple of different systemic agents already. If they’re started on enzalutamide or apalutamide in the nonmetastatic space, then they’ve already been through 1 androgen receptor access–targeted agent. Potentially, in the metastatic hormone-sensitive space, they may have already been through chemotherapy.
When the patient develops castrate-resistant metastatic disease, chances are the treatment options are going to be limited because the patients have potentially been pretreated with 2 different mechanisms. At that time, I think risk profiling is going to be critical. For patients with predominantly bone disease, using radium-223 or considering it would make sense. For patients with specific genomic markers that are found in about 10% to 20% of metastatic prostate cancer, genomic profiling would serve the purpose of selecting patients for treatment such as PARP [poly ADP ribose polymerase] inhibitors for DNA repair mutations or PI3 [phosphoinositide 3]-kinase inhibitors for PTEN [phosphatase and tensin homolog] loss, etcetera.
Evan Yu, MD: Metastatic castration resistance in prostate cancer is an evolving field. We already have many FDA-approved treatment options that are prolonging the survival of our patients. I think that as we learn more and more from clinical trials, we’ll not only have newer agents to add to the treatment paradigm, but we’ll also be able to use existing agents better. Perhaps new combinations and better understandings of the sequencing will be coupled with all the next-generation sequencing that’s occurring now. I think we’re going to be able to better select our patients for the right therapies that work for them, and hopefully deselect patients from therapies that might not work well for them.
I think there are a lot of opportunities right now to develop new agents for castration-resistant prostate cancer because many of the agents we use in that setting are being moved earlier into hormone-sensitive disease or M0 [nonmetastatic] castration-resistant disease. What happens downstream for those patients when they progress on that leads us to drugs like radium and docetaxel. But there’s an unmet need. We need to develop new drugs, and there are a lot of new exciting agents out there. I look forward to the future, where we’re going to select better therapy for our patients, sequence therapy better, and have new agents in the treatment paradigm.