Early data from ongoing clinical trials suggest the potential safety and efficacy of novel radium-223 combinations as treatment for metastatic castration-resistant prostate cancer.
Future research will look to affirm the overall survival (OS) and safety benefits of radium-223 in combination with agents including docetaxel in metastatic castration-resistant prostate cancer (mCRPC) studies such as the phase 3 DORA trial (NCT03574571), according to Scott T. Tagawa, MD, MS, FACP.
Tagawa, a professor of medicine and urology and medical director of the Genitourinary Oncology Research Program at Weill Cornell Medicine, spoke with CancerNetwork® at the 16th Annual Interdisciplinary Prostate Cancer Congress® and Other Genitourinary Malignancies regarding ongoing clinical trials investigating the efficacy of different radium-223 combination therapies in mCRPC.
There are a couple of ongoing phase 3 trials. One is a trial called PEACE III [NCT02194842], which is taking a patient population [with] untreated mCRPC—meaning frontline—with the backbone enzalutamide [Xtandi] with or without radium-223. This trial started with the benefit early on of knowing the phase 3 ERA 223 trial [NCT02043678] results. Early on, they mandated the use of bone health agents. We’ve seen a couple of initial safety presentations at [the American Society of Clinical Oncology Annual Meeting] that demonstrate that there’s no excess fractures to date, although we’re waiting for the overall efficacy results of that study.1
And then a separate combination study, based upon a PCC TC randomized phase 2 study [NCT01106352] led by [Michael J. Morris, MD], [is evaluating] docetaxel and radium-223. Again, [it] makes sense targeting different compartments and also [with the] radiosensitizing properties of the taxane. That randomized phase 2 trial showed improvements in efficacy with lower toxicity to the combination.2 Now, the combination is an adjusted dose and schedule, so docetaxel at 60 mg/m2 and radium-223 every 6 weeks to match with the docetaxel. In any case, that has led to the phase 3 DORA trial, which is ongoing [with] accrual, with probably more than a third still left to go. But what we’re hoping to see is an [OS] benefit, maybe with an improved safety profile.