OVERALL SURVIVAL

    XOFIGO SIGNIFICANTLY EXTENDS OVERALL SURVIVAL (OS)1,2

    PRESPECIFIED INTERIM OS ANALYSIS

    Median OS was 14.0 months (95% CI: 12.1-15.8) for Xofigo + best standard of care (BSOC) vs 11.2 months for BSOC (95% CI: 9.0-13.2). Hazard ratio (HR)=0.695 (95% CI: 0.552-0.875) P=0.00185.1,2

     

    MEDIAN OS IN AN UPDATED EXPLORATORY ANALYSIS1,2

    30% reduction in the risk of death vs. best standard of care
    • ​​Evaluated in the ALSYMPCA trial: double-blind, randomized, placebo-controlled, phase III study of 921 patients with castration-resistant prostate cancer with symptomatic bone metastases and no known visceral metastatic disease1,2
    • At the preplanned interim analysis, 809 patients were randomized to receive Xofigo 55 kBq (1.49 microcurie)/kg intravenously every 4 weeks for 6 cycles (n=541) + BSOC or BSOC (n=268); statistically significant improvement seen in interim analysis1
    • An exploratory updated analysis was performed before patient crossover, incorporating an additional 214 events, resulting in findings consistent with the interim analysis1
    • BSOC was defined as antiandrogens, local external-beam radiation therapy, ketoconazole, estrogens, estramustine, or treatment with glucocorticoids2

     

    GIVE YOUR PATIENTS THE SURVIVAL BENEFIT WITH 6 INJECTIONS OF XOFIGO: A 1-MINUTE INJECTION EVERY 4 WEEKS.

      OS ANALYSES BY PRESPECIFIED SUBGROUPS1

      PRESPECIFIED SUBGROUP SURVIVAL ANALYSIS FROM ALSYMPCA1

      Prespecified subgroup survival analysis from ALSYMPCA

      Adapted from Parker, et al.

      • The primary endpoint of the ALSYMPCA study was OS2
      • Patients were stratified into the following subgroups at randomization: prior docetaxel exposure, current bisphosphonate use, and total ALP2
      • These subgroup analysis data are descriptive in nature—the study was not powered to detect treatment differences in OS specifically within these prestratified subgroups

       

      aPlus best standard of care.

        OS ANALYSES BY PRESPECIFIED SUBGROUPS: PRIOR DOCETAXEL USE

        MEDIAN INCREASE IN OS WITH XOFIGO FROM ALSYMPCA2

        Median increase in overall survival with Xofigo®
        • The primary endpoint of the ALSYMPCA study was OS2
        • Patients were stratified into the following subgroups at randomization: prior docetaxel exposure, current bisphosphonate use, and total ALP2
        • These subgroup analysis data are descriptive in nature—the study was not powered to detect treatment differences in OS specifically within these prestratified subgroups

         

        BSOC=Best Standard of Care; CI=Confidence Interval.

        References
        • Xofigo® (radium Ra 223 dichloride) injection [prescribing information]. Whippany, NJ: Bayer HealthCare Pharmaceuticals Inc.; December 2019. Return to content
        • Parker C, Nilsson S, Heinrich D, et al. Alpha emitter radium-223 and survival in metastatic prostate cancer. N Engl J Med. 2013;369(3):213-223. Return to content

        Indication

        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

        Warnings and Precautions:
        • 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

         

        • 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

         

        • Concomitant Use With Chemotherapy: Safety and efficacy of concomitant chemotherapy 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

         

        • 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 dichloride, 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%)

        For important risk and use information about Xofigo, please see the Full Prescribing Information.

        You are encouraged to report side effects or quality complaints of products to the FDA by visiting www.fda.gov/medwatch or calling 1-800-FDA-1088. For Bayer products, you can report these directly to Bayer by clicking here.