Benjamin L. Maughan, MD, PharmD
A phase II trial evaluating the combination of radium-223 dichloride (Xofigo) and enzalutamide (Xtandi) met its primary endpoint of reducing bone metabolism markers in patients with metastatic castration-resistant prostate cancer (mCRPC), according to data presented at the 2018 ESMO Congress.1
, Maughan, a genitourinary medical oncologist, assistant professor in the Division of Medical Oncology, Huntsman Cancer Institute, discussed the activity of the combination of radium-223 and enzalutamide in patients with mCRPC.
OncLive: Could you tell us about the phase II trial evaluating the radium-223/enzalutamide combination in mCRPC?
: This [trial] is just testing a hypothesis that has been proven in the metastatic hormone-sensitive space, which is the idea that intensifying treatment upfront is more efficient than sequential single-agent therapy. This is not the only the study to test this hypothesis in [patients with] metastatic CRPC, but it is in the same theme. [For the trial], we looked at men who had bone-only metastases. We randomized them in a 2:1 fashion to receive either the combination of radium-223 and enzalutamide or enzalutamide alone.
What are the findings reported thus far?
Earlier, at the 2018 ASCO Annual Meeting, we reported safety data for this combination. [The rationale for this] was due, in part, to a press release that came out looking at a similar combination, abiraterone acetate plus prednisone plus radium-223. In that study, we saw an increased risk of death and fractures in the combination arm versus the control arm. In our study, we found that the combination [of radium-223 and enzalutamide] was safe. Cytopenias were observed at the same rate as radium-223 alone. Importantly, when we reported this at the 2018 ASCO Annual Meeting, there were no fractures in our patients.
At the 2018 ESMO Congress, [we reported] on the efficacy [of the combination]. In terms of the primary endpoint of reduction in bone metabolism markers, we saw a significant decrease in the change of bone metabolism markers from the time of enrollment to the end of the radium-223 period. The combination was more effective in reducing bone metabolism markers compared with [the use of] enzalutamide alone. We think this [finding] is reflective of better disease control. We say this because one of the secondary endpoints was prostate-specific antigen (PSA) response, and PSA progression-free survival was longer in the combination [arm].
What are the next steps for this research?
Overall, what [these findings] demonstrate is the hypothesis that has been proven true in the hormone-sensitive space, is likely better in the castration-resistant setting as well: Intensive therapy is better. The key is to find therapies that are tolerable together. This is a particularly important point, especially at the 2018 ESMO Congress, where the full data on that press release I mentioned earlier was presented. We saw no additional safety signals in our study. Only 2 patients in our study were on bone-modifying therapy, while about 35% of the patients in the other study were.
What are some exciting therapies coming down the pike in prostate cancer?
First of all, we would like to see validated results of [data presented at the 2018 ESMO Congress] in the surgical setting. That would substantially change how we think about and treat a large population of men with prostate cancer; it would also open a whole new avenue of treatment for those with oligometastases. Not only should we treat the prostate, but what about aggressive systemic therapy also directed at the metastases? This would allow us to personalize therapy even more.
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