A radium-223 and enzalutamide doublet therapy was associated with a significant long-term clinical benefit compared with enzalutamide monotherapy in patients with progressive metastatic castration-resistant prostate cancer (mCRPC), according to the final efficacy and safety results of a phase 2 study presented at the 2021 Genitourinary Cancers Symposium.
Data from a previous analysis of the trial (NCT02199197) demonstrated that radium-223 plus enzalutamide decreased serum bone metabolism markers, correlating with improved outcomes. The investigators randomly assigned 35 patients with progressive mCRPC to receive radium-223 plus enzalutamide; the remaining 12 patients enrolled on the trial received enzalutamide monotherapy.
The primary end points—change in bone markers and safety—were previously reported. Secondary end points included prostate-specific antigen (PSA) progression-free survival (PFS), overall survival (OS), and long-term safety. Post hoc analyses included a comparison of time to PSA progression on subsequent therapy (PSA-PFS2), and time to subsequent/next therapy (TTNT).
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At a median follow-up of 22 months, the median PSA-PFS was 8.9 months with radium-223 plus enzalutamide vs 3.38 months with enzalutamide alone (P =.97). The median OS was 30.8 months with the combination approach compared with 20.6 months with enzalutamide monotherapy (P =.73).
Further, the PSA-PFS2 was significantly longer with the doublet therapy, at a median of 18.7 months compared with 8.41 months with enzalutamide (P =.033). Radium-223 plus enzalutamide also resulted in a TTNT of 15.9 months compared with 3.47 months with single-agent enzalutamide (P =.067).
Two of 35 patients in the combination group developed grade 1 asymptomatic fracture at the site of bone metastasis; however, no such cases were seen in the enzalutamide group. There were no reports of bone marrow disorders in either treatment arm.
“Enzalutamide plus radium-223 resulted in significant long-term clinical benefit over enzalutamide alone in patients with mCRPC without compromising safety,” concluded lead author Adam Kessel, who presented the findings.
Disclosures: Some of the study authors disclosed financial relationships with the pharmaceutical industry and/or the medical device industry. For a full list of disclosures, please refer to the original study. This research was supported by Bayer.
Reference
Kessel A, McFarland TR, Sayegh N, et al. Randomized phase II trial of radium-223 (RA) plus enzalutamide (EZ) versus EZ alone in metastatic castration-refractory prostate cancer (mCRPC): final efficacy and safety results. Presented at: 2021 Genitourinary Cancers Symposium; February 11-13, 2021. Abstract 135.
