Important Safety Information



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.

Please see additional Important Safety Information continued below.

Indication
Xofigo is indicated for the treatment of patients with castration-resistant prostate cancer, symptomatic bone metastases and no known visceral metastatic disease.

Xofigo Significantly Extends Overall Survival1,2

The efficacy and safety of Xofigo were evaluated in the double-blind, randomized, placebo-controlled ALSYMPCA trial. The primary end point was overall survival (OS).1,2

921 patients with castration-resistant prostate cancer (CRPC), symptomatic bone metastases, and no known visceral metastatic disease were randomized 2:1 to receive either Xofigo 55 kBq (1.49 µCi)/kg every 4 weeks for 6 cycles plus best standard of care (BSOC) or placebo plus BSOC. BSOC was defined as antiandrogens, ketoconazole, local external beam radiation therapy (EBRT), estrogens, estramustine, or treatment with glucocorticoids. At the cutoff date for a preplanned interim analysis, 541 patients had been randomized to receive Xofigo plus BSOC, while 268 had been randomized to placebo plus BSOC.1,2

Give your patients the survival benefit with 6 injections of Xofigo:

Prespecified interim analysis: Median OS in the prespecified interim analysis was 14.0 months (95% confidence interval [CI]: 12.1-15.8) for Xofigo + BSOC vs 11.2 months for placebo + 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

An exploratory updated analysis was performed before patient crossover, incorporating an additional 214 events, resulting in findings consistent with the interim analysis. As shown in the figure above, median OS in the exploratory updated analysis was 14.9 months (95% CI: 13.9-16.1) for patients receiving Xofigo plus BSOC (n=614) vs 11.3 months (95% CI: 10.4-12.8) for those receiving placebo plus BSOC (n=307). HR=0.695 (95% CI: 0.581-0.832).1,2

These findings reflect a 30% reduction in the risk of death with Xofigo plus BSOC relative to placebo plus BSOC.

Xofigo Significantly Delays Time to First Symptomatic Skeletal Event1,2,a

Time to first symptomatic skeletal event (SSE) was a prespecified secondary efficacy end point in ALSYMPCA. SSEs were defined as EBRT to relieve skeletal symptoms, spinal cord compression, tumor-related orthopedic surgical intervention, and new symptomatic pathologic bone fractures.1,2

Median time to first SSE in the trial’s Xofigo plus BSOC arm was 15.6 months, vs 9.8 months in the placebo plus BSOC arm (HR=0.66; 95% CI: 0.52-0.83; P<0.001).2 That 5.8-month increase in time to first SSE translated into a 34% risk reduction in time to first SSE.2 Thus, the survival results seen in ALSYMPCA were supported by a delay in the time to first SSE favoring the Xofigo plus BSOC arm. The majority of events consisted of EBRT to bone metastases.
1

Median Time

Xofigo Brochure
For more information on OS and
SSEs, download a copy of the
brochure by clicking on the
Xofigo brochure image.
Important Safety Information (cont)
 
Warnings and Precautions (cont):
  • Bone Marrow Suppression (cont): 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.

Xofigo Has a Well-Established Safety Profile1

In the phase 3 ALSYMPCA trial, the most common adverse reactions (≥10%) in the Xofigo arma 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.1

The most common hematologic laboratory abnormalities in the Xofigo arm (≥10%) vs the placebo arm (all grades [%]), respectively, were anemia (93% vs 88%), lymphocytopenia (72% vs 53%), leukopenia (35% vs 10%), thrombocytopenia (31% vs 22%), and neutropenia (18% vs 5%).1

Treatment discontinuations due to adverse events occurred in 17% of patients who received Xofigo and 21% of patients who received placebo.1

For more information on the Safety Data from the ALSYMPCA Trial, please visit
https://hcp.xofigo-us.com/prescribe-xofigo/safety/safety-profile/

aPlus BSOC, which was defined as antiandrogens, ketoconazole, local EBRT, estrogens, estramustine, or treatment with glucocorticoids1,2

Xofigo Is Recommended by All Major Prostate Cancer Guidelines
NCCN Guidelines

NCCN Guidelines and National Comprehensive Cancer Network® are registered trademarks of National Comprehensive Cancer Network, Inc. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Prostate Cancer v.4.2019. National Comprehensive Cancer Network, Inc. 2019. All rights reserved. Accessed December 18, 2019. To view the most recent and complete version of the guideline, go online to NCCN.org. NATIONAL COMPREHENSIVE CANCER NETWORK®, NCCN®, NCCN GUIDELINES® , and all other NCCN content are trademarks owned by the National Comprehensive Cancer Network, Inc.

Indication
Xofigo is indicated for the treatment of patients with castration-resistant prostate cancer, symptomatic bone metastases and no known visceral metastatic disease.

Start Xofigo When Your Patient Has . . .
patients

aSerum PSA progression defined as 2 consecutive increases in PSA over a previous reference.
bIn the ALSYMPCA clinical trial, Xofigo was given with BSOC, which included antiandrogens, ketoconazole, local EBRT, estrogens, estramustine, or treatment with glucocorticoids.
 

Checklist Brochure
For more information on identifying candidates for Xofigo and to download
a copy of the Patient Identification Checklist, click on the brochure image.
See How the Xofigo Rebate Program Could Impact Your Practice

Your Bayer Oncology Account Manager could review your current rebate performance and begin planning for your next quarter tier and rebate goals.

month-chart
Select practice requirements: Only accounts with signed letters of declaration with GPOs that have executed Xofigo contracts with Bayer HealthCare are eligible for participation in the back-end rebate program.

month-chart

Note: Parent Accounts must have a minimum of four hundred (400) microcuries (µCi) or greater in the Initial Baseline/Baseline period.
contact
Contact Xofigo Access Services
at 1-855-6XOFIGO (1-855-696-3446)


up to 7 business days prior to each patient’s scheduled treatment date
to order Xofigo with Cardinal Health Nuclear Pharmacy Services

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 x 109/L, the platelet count ≥100 x 109/L, and hemoglobin ≥10 g/dL. Prior to subsequent administrations, the ANC should be ≥1 x 109/L and the platelet count ≥50 x 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 (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.

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For more information about Xofigo, please visit us at http://hcp.xofigo-us.com or contact your Bayer Sales Representative.

References

  1. Xofigo (radium Ra 223 dichloride) injection [prescribing information]. Whippany, NJ: Bayer HealthCare Pharmaceuticals Inc.; December 2019.
  2. 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.
  3. Mohler JL et al. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) Prostate Cancer. Version 4.2019. National Comprehensive Cancer Network. 2019:1-166.
  4. Basch E, Loblaw DA, Oliver TK, et al. Systemic therapy in men with metastatic castration-resistant prostate cancer: American Society of Clinical Oncology and Cancer Care Ontario Clinical Practice Guideline. J Clin Oncol. 2014;32(30):3436-3448.
  5. Scher HI, Morris MJ, Stadler WM, et al. Trial design and objectives for castration-resistant prostate cancer: updated recommendations from the Prostate Cancer Clinical Trials Working Group 3. J Clin Oncol. 2016;34(12):1402-1418.
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