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.


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.