- New data from the Phase III PEACE III trial showed that XOFIGO® (radium-223 dichloride) in combination with enzalutamide significantly improved prostate-specific antigen (PSA) response rates (≥90% at 6 and 12 months; 50.5% and 54.9% respectively) compared to enzalutamide alone (34.1% and 37.6% respectively) and the median time to alkaline phosphatase (ALP) normalization was 1.97 months for XOFIGO plus enzalutamide versus 4.47 months for enzalutamide alone (HR 1.42; 95% CI 1.13-1.80) among patients with metastatic castration-resistant prostate cancer (mCRPC) with bone metastases
- Results from the Phase II COMRADE clinical trial demonstrated that the combination of olaparib with XOFIGO significantly improved radiographic progression-free survival (rPFS) compared to XOFIGO alone in mCRPC patients with bone metastases, with a median of 8.6 months versus 4.0 months (HR 0.51; 80% CI, 0.37-0.70; 2-sided p=0.005)
- Results from the two trials will be presented at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting
WHIPPANY, N.J.--(BUSINESS WIRE)--New data from two clinical trials evaluating XOFIGO® (radium-223 dichloride) in patients with metastatic castration-resistant prostate cancer (mCRPC) with bone metastases will be presented at the American Society of Clinical Oncology (ASCO) 2025 Annual Meeting on June 3, 2025. The studies in prostate cancer treatment with XOFIGO, offer potential new insights for patients with mCRPC with bone metastases.
XOFIGO is indicated for the treatment of patients with CRPC, symptomatic bone metastases and no known visceral metastatic disease.1 It is the first and only alpha emitting radiopharmaceutical that treats bone metastases in mCRPC approved by the U.S. Food and Drug Administration (FDA).
An analysis from the pivotal Phase III PEACE III trial, evaluating XOFIGO in combination with enzalutamide, an androgen receptor pathway inhibitor (ARPI), showed that adding six cycles of XOFIGO to enzalutamide improved prostate-specific antigen (PSA) and alkaline phosphatase (ALP) response rates.2 Notably, PSA response rates ≥90% at 6 and 12 months were 50.5% and 54.9%, respectively, in the combination arm compared to 34.1% and 37.6%, respectively, in the enzalutamide arm alone.2 The analysis also showed that for XOFIGO in combination with enzalutamide the median time to ALP normalization was 1.97 months compared to 4.47 months in the enzalutamide arm (HR 1.42; 95% CI, 1.13-1.80).2
The analysis follows the presentation of the full results from the PEACE III trial, presented as a late-breaking abstract during the Presidential Symposium at ESMO 2024.3 The results demonstrated that the addition of XOFIGO to enzalutamide significantly increased radiological progression-free survival (rPFS) among patients with mCRPC with bone metastases, with a 31% reduction in the risk of progression or death (HR 0.69; 95% CI, 0.54-0.87; p=0.0009) compared to enzalutamide alone.3 At the preplanned interim analysis conducted at 80% of the overall survival (OS) events, the hazard ratio (HR) for OS was 0.69 (95% CI 0.52-0.90; p=0.0031). The safety results were consistent with the established safety profile of XOFIGO, although authors noted the importance of administering bone protective agents (BPAs) to avoid fractures.3 The trial was a collaboration between the European Organization for Research and Treatment of Cancer (EORTC), Clinical Trial Ireland (CTI), the Canadian Urological Oncology Group (CUOG), the Latin American Cooperative Oncology Group (LACOG), and French UNICANCER Urogenital Tumor Study Group (GETUG).
The results were consistent with the established safety profile of XOFIGO. Grade 3 or higher treatment emergent adverse events (TEAE) were recorded in 65.6% of patients in the combination arm compared to 55.8% of patients who received enzalutamide alone.2 The most frequent Grade 3 or higher TEAEs in the combination arm were hypertension (34%), fatigue (6%), fracture (5%), anemia (5%) and neutropenia (5%).2 Fractures (either treatment-emergent or post-treatment, symptomatic or pathologic, or with or without BPA use) were reported in 24.3% of patients in the combination arm and in 13.4% of patients in the enzalutamide arm.2
"The PEACE III trial has provided us with valuable insights into the benefits of combining XOFIGO with enzalutamide for patients with metastatic castration-resistant prostate cancer with bone metastases," said Dr. Murilo Luz, Urologic Oncologist, The Mount Sinai Hospital, New York and trial investigator. "This analysis highlights that the combination therapy achieved improvements on PSA and ALP, beyond the known radiographic progression free survival benefit. We are encouraged by these results with this potential compelling therapeutic option, which could provide an additional treatment option for patients."
Data from the Phase II COMRADE trial were also presented at the ASCO 2025 Annual Meeting. Results demonstrated that the combination of olaparib with XOFIGO significantly improved radiographic progression-free survival (rPFS) in mCRPC patients compared to XOFIGO alone, with a median of 8.6 months versus 4.0 months (HR 0.51; 80% CI, 0.37-0.70; 2-sided p=0.005).4 56% of patients in the olaparib with XOFIGO and 35% of patients in the XOFIGO arms had grade ≥3 treatment-related adverse events, the most common adverse events on the olaparib with XOFIGO and XOFIGO arms were anemia (22.0%/18.0%), lymphocyte decrease (30.5%/9.1%), platelet decrease (6.8%/3.6%), and neutrophil decrease (5.1%/7.3%), respectively.4
"The results from the PEACE III and COMRADE trials underscore our dedication to exploring combinations, such as XOFIGO with enzalutamide or olaparib. We are hopeful these results will introduce another treatment option for patients with mCRPC and bone metastases who have not progressed viscerally,” said Christine Roth, Executive Vice President, Global Product Strategy and Commercialization and Member of the Pharmaceuticals Leadership Team at Bayer.
About PEACE III (EORTC GUCG-1333)
The PEACE III trial is an international, randomized, open-label, Phase III trial designed to investigate the efficacy and safety of XOFIGO in combination with enzalutamide in patients with metastatic castration-resistant prostate cancer (mCRPC) and bone metastases. A total of 446 patients were randomized 1:1 to receive either XOFIGO 55 kBq/kg as an intravenous injection monthly for six cycles in combination with enzalutamide 160mg orally daily or enzalutamide 160mg orally daily.
The primary endpoint was radiological progression-free survival (rPFS) by investigator assessment. Key secondary endpoints included overall survival (OS), time to subsequent systemic treatment, pain progression, and symptomatic skeletal event. This trial was a collaboration with several cancer cooperative groups: EORTC, CTI, CUOG, LACOG, and GETUG.
About COMRADE II
COMRADE is an open-label, randomized Phase II investigator-initiated trial in patients with metastatic castration resistant prostate cancer with bone metastases treated with a combination of olaparib, a PARP inhibitor, and XOFIGO compared to XOFIGO alone, 120 patients were randomized 1:1 to receive either olaparib plus XOFIGO or XOFIGO alone. The primary endpoint was radiographic progression-free survival (rPFS).
About XOFIGO® (radium-223 dichloride) Injection1
XOFIGO is indicated for the treatment of patients with castration-resistant prostate cancer, symptomatic bone metastases and no known visceral metastatic disease.
Important Safety Information for Xofigo® (radium-223 dichloride) Injection
Warnings and Precautions:
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Bone Marrow Suppression: In the phase 3 ALSYMPCA trial, 2% of patients in the Xofigo arm experienced bone marrow failure or ongoing pancytopenia, compared to no patients treated with placebo. There were two deaths due to bone marrow failure. For 7 of 13 patients treated with Xofigo bone marrow failure was ongoing at the time of death. Among the 13 patients who experienced bone marrow failure, 54% required blood transfusions. Four percent (4%) of patients in the Xofigo arm and 2% in the placebo arm permanently discontinued therapy due to bone marrow suppression. In the randomized trial, deaths related to vascular hemorrhage in association with myelosuppression were observed in 1% of Xofigo-treated patients compared to 0.3% of patients treated with placebo. The incidence of infection-related deaths (2%), serious infections (10%), and febrile neutropenia (<1%) was similar for patients treated with Xofigo and placebo. Myelosuppression–notably thrombocytopenia, neutropenia, pancytopenia, and leukopenia–has been reported in patients treated with Xofigo.
Monitor patients with evidence of compromised bone marrow reserve closely and provide supportive care measures when clinically indicated. Discontinue Xofigo in patients who experience life-threatening complications despite supportive care for bone marrow failure
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Hematological Evaluation: Monitor blood counts at baseline and prior to every dose of Xofigo. Prior to first administering Xofigo, the absolute neutrophil count (ANC) should be ≥1.5 × 109/L, the platelet count ≥100 × 109/L, and hemoglobin ≥10 g/dL. Prior to subsequent administrations, the ANC should be ≥1 × 109/L and the platelet count ≥50 × 109/L. Discontinue Xofigo if hematologic values do not recover within 6 to 8 weeks after the last administration despite receiving supportive care
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Concomitant Use With Chemotherapy: Safety and efficacy of concomitantchemotherapy with Xofigo have not been established. Outside of a clinical trial, concomitant use of Xofigo in patients on chemotherapy is not recommended due to the potential for additive myelosuppression. If chemotherapy, other systemic radioisotopes, or hemibody external radiotherapy are administered during the treatment period, Xofigo should be discontinued
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Increased Fractures and Mortality in Combination With Abiraterone Plus Prednisone/Prednisolone: Xofigo is not recommended for use in combination with abiraterone acetate plus prednisone/prednisolone outside of clinical trials. At the primary analysis of the Phase 3 ERA-223 study that evaluated concurrent initiation of Xofigo in combination with abiraterone acetate plus prednisone/prednisolone in 806 asymptomatic or mildly symptomatic mCRPC patients, an increased incidence of fractures (28.6% vs 11.4%) and deaths (38.5% vs 35.5%) have been observed in patients who received Xofigo in combination with abiraterone acetate plus prednisone/prednisolone compared to patients who received placebo in combination with abiraterone acetate plus prednisone/prednisolone. Safety and efficacy with the combination of Xofigo and agents other than gonadotropin-releasing hormone analogues have not been established
- Embryo-Fetal Toxicity: The safety and efficacy of Xofigo have not been established in females. Xofigo can cause fetal harm when administered to a pregnant female. Advise pregnant females and females of reproductive potential of the potential risk to a fetus. Advise male patients to use condoms and their female partners of reproductive potential to use effective contraception during and for 6 months after completing treatment with Xofigo
Administration and Radiation Protection: Xofigo should be received, used, and administered only by authorized persons in designated clinical settings. The administration of Xofigo is associated with potential risks to other persons from radiation or contamination from spills of bodily fluids such as urine, feces, or vomit. Therefore, radiation protection precautions must be taken in accordance with national and local regulations
Fluid Status: Dehydration occurred in 3% of patients on Xofigo and 1% of patients on
placebo. Xofigo increases adverse reactions such as diarrhea, nausea, and vomiting, which may result in dehydration. Monitor patients’ oral intake and fluid status carefully and promptly treat patients who display signs or symptoms of dehydration or hypovolemia
Injection Site Reactions: Erythema, pain, and edema at the injection site were reported in 1% of patients on Xofigo
Secondary Malignant Neoplasms: Xofigo contributes to a patient’s overall long-term cumulative radiation exposure. Long-term cumulative radiation exposure may be associated with an increased risk of cancer and hereditary defects. Due to its mechanism of action and neoplastic changes, including osteosarcomas, in rats following administration of radium-223, Xofigo may increase the risk of osteosarcoma or other secondary malignant neoplasms. However, the overall incidence of new malignancies in the randomized trial was lower on the Xofigo arm compared to placebo (<1% vs 2%; respectively), but the expected latency period for the development of secondary malignancies exceeds the duration of follow-up for patients on the trial
Subsequent Treatment With Cytotoxic Chemotherapy: In the randomized clinical trial, 16% of patients in the Xofigo group and 18% of patients in the placebo group received cytotoxic chemotherapy after completion of study treatments. Adequate safety monitoring and laboratory testing was not performed to assess how patients treated with Xofigo will tolerate subsequent cytotoxic chemotherapy
Adverse Reactions: The most common adverse reactions (≥10%) in the Xofigo arm vs the placebo arm, respectively, were nausea (36% vs 35%), diarrhea (25% vs 15%), vomiting (19% vs 14%), and peripheral edema (13% vs 10%). Grade 3 and 4 adverse events were reported in 57% of Xofigo-treated patients and 63% of placebo-treated patients. The most common hematologic laboratory abnormalities in the Xofigo arm (≥10%) vs the placebo arm, respectively, were anemia (93% vs 88%), lymphocytopenia (72% vs 53%), leukopenia (35% vs 10%), thrombocytopenia (31% vs 22%), and neutropenia (18% vs 5%).
Please see the full Prescribing Information for Xofigo (radium 223 dichloride).
About Oncology at Bayer
Bayer is committed to delivering science for a better life by advancing a portfolio of innovative treatments. The oncology franchise at Bayer includes six marketed products and several other assets in various stages of clinical development. Together, these products reflect the company’s approach to research, which prioritizes targets and pathways with the potential to impact the way that cancer is treated.
About Bayer
Bayer is a global enterprise with core competencies in the life science fields of health care and nutrition. In line with its mission, “Health for all, Hunger for none,” the company’s products and services are designed to help people and the planet thrive by supporting efforts to master the major challenges presented by a growing and aging global population. Bayer is committed to driving sustainable development and generating a positive impact with its businesses. At the same time, the Group aims to increase its earning power and create value through innovation and growth. The Bayer brand stands for trust, reliability and quality throughout the world. In fiscal 2024, the Group employed around 93,000 people and had sales of 46.6 billion euros. R&D expenses before special items amounted to 6.2 billion euros. For more information, go to www.bayer.com.
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This release may contain forward-looking statements based on current assumptions and forecasts made by Bayer management. Various known and unknown risks, uncertainties and other factors could lead to material differences between the actual future results, financial situation, development or performance of the company and the estimates given here. These factors include those discussed in Bayer’s public reports which are available on the Bayer website at www.bayer.com. The company assumes no liability whatsoever to update these forward-looking statements or to conform them to future events or developments.
References
- XOFIGO® (radium-223) Injection [Prescribing Information]. Whippany, NJ: Bayer HealthCare Pharmaceuticals, December 2019.
- Choudhury A, et al. PSA and alkaline phosphatase changes in the EORTC-1333 PEACE-3 study evaluating the addition of six cycles of radium 223 in metastatic castration-resistant prostate cancer (mCRPC) starting enzalutamide. Abstract 5062. Presented at ASCO 2025.
- Gillessen S, et al. A randomized multicenter open label phase III trial comparing enzalutamide vs a combination of Radium-223 (Ra223) and enzalutamide in asymptomatic or mildly symptomatic patients with bone metastatic castration-resistant prostate cancer (mCRPC): First results of EORTC-GUCG 1333/PEACE-3. European Society of Medical Oncology 2025 (ESMO) LBA1. September 9, 2024.
- McKay RR, et al. A multicenter, randomized, phase 2, investigator-initiated ETCTN trial of olaparib + radium-223 vs. radium-223 in men with castration-resistant prostate cancer (CRPC) with bone metastases (BM) (COMRADE): Initial efficacy and biomarker analysis. Abstract 5007. Presented at ASCO 2025.
Contacts
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Email: polina.miklush@bayer.com
