(UroToday.com) The 2026 PSMA & Beyond conference featured a clinical trial updates session and presentation by Dr. Michael Morris discussing DORA and PEACE-3 and the evolving role of radium-223. Dr. Morris started by highlighting that radium-223 is beyond PSMA in many respects, including:
- The first and still the only alpha emitter approved for prostate cancer
- The first radiotherapeutic to prolong survival in prostate cancer
- The first bone-directed therapy to earn approval on the basis of overall survival and to preserve quality of life
- Radium-223 is still the only therapy in prostate cancer to successfully target the tumor microenvironment
The following table highlights the phase III trials involving radium-223:
PEACE-3 is the second phase III radium-223 trial to demonstrate an overall survival benefit [1].
This was a randomized, open-label, multicenter phase III trial evaluating the addition of radium-223 to enzalutamide in mCRPC with bone metastases. In PEACE-3, a total of 446 asymptomatic or mildly symptomatic patients (Brief Pain Inventory <4) with mCRPC and ≥2 bone metastases were randomized 1:1 to enzalutamide 160 mg daily alone or combined with six intravenous injections of radium-223 (55 kBq/kg every 4 weeks):
The final radiographic progression-free survival analysis continued to show a benefit for enzalutamide + radium 223 (HR 0.71, 95% CI 0.57-0.89):
The median overall survival was 38.21 months for enzalutamide + radium 223 and 32.62 months for enzalutamide alone, corresponding to a hazard ratio of 0.76 (95% CI 0.60–0.96; one-sided stratified log rank p-value 0.0096, with a preset level of significance at final analysis of < 0.0248). Based on the permutation test, the statistical test on overall survival is significant (resulting in a 1-sided p-value of 0.0088 < 0.0248):
The overall survival benefit was consistent across most predefined subgroups, except for age >75 years, for which the interaction was significant at the 10% 2-sided level. The updated safety analysis demonstrated no new signals, with 28.9% of patients receiving enzalutamide + radium 223 have a grade 3-5 drug-related, treatment-emergent adverse event, compared to 18.8% for those receiving enzalutamide alone. The summary of treatment emergent adverse events grade 3+ is as follows, most notably hypertension being the most common:
Side effects of special interest included one patient with myelodysplastic syndrome, one with AML, and one with CML, all of which were in the enzalutamide + radium 223 combination arm. Moreover, there were 17 patients with osteonecrosis of the jaw, including 14 patients in the enzalutamide + radium 223 group (five with grade 3), and 3 in the enzalutamide monotherapy arm. The following table highlights the PEACE-3 results in the context of other first-line mCRPC therapies available:
The DORA trial represents a platform for dual targeting of the bone microenvironment and tumor. In DORA, 738 patients with mCRPC were randomized 1:1 to docetaxel or docetaxel + radium-223, with a projected hazard ratio for treatment effect (15 versus 20 months median survival) of 0.75. The trial design for DORA is as follows:
The accrual goal for DORA was met in October 2025, with the last patient’s last visit projected for May 2026. The primary endpoint of overall survival is projected for late 2026.
Dr. Morris concluded his presentation discussing DORA and PEACE-3 and the evolving role of radium-223with the following take-home points:
- Radium-223 should not be forgotten as a means of addressing the prostate cancer bone microenvironment using a theranostic approach
- Combination with androgen receptor pathway inhibitors in certain settings yields an overall survival advantage not seen in any other prostate cancer study
- Combination with chemotherapy in DORA should yield a result in the fourth quarter of 2026
Presented by: Michael Morris, MD, Memorial Sloan Kettering Cancer Center, New York, NY
Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Associate Professor of Urology, Georgia Cancer Center, Wellstar MCG Health, @zklaassen_md on Twitter during the 2026 PSMA & Beyond Conference, Los Angeles, CA, Thurs, Mar 26 – Fri, Mar 27, 2026.
Related content: DORA and PEACE-3: Evolving Role of Ra-223 "Presentation" - Michael Morris
References: