SAFETY

Safety: Overall Grade 3-4 Adverse Events

Well-documented safety profile: Overall Grade 3-4 adverse events (AEs) were similar to BSOC¹

GRADE 3-4 AEs WERE REPORTED IN 57% OF XOFIGO^®-TREATED PATIENTS AND 63% OF PLACEBO-TREATED PATIENTS¹

ADVERSE REACTIONS OCCURRING IN ≥2% OF PATIENTS IN THE RANDOMIZED TRIAL^1,a

Xofigo® adverse reactions occurring in greater than or equal to 2% of patients

aFor which the rates for Xofigo exceed the rates for placebo.¹

bPlus best standard of care (BSOC).¹

HEMATOLOGIC LABORATORY ABNORMALITIES OCCURRING IN ≥10% OF PATIENTS^1,a,b

Hematologic laboratory abnormalities occurring in greater than or equal to 10% of patients

aThe same patients (Xofigo, 600; placebo, 301) as in the adverse reactions patient population.

bFor which the rates for Xofigo exceed the rates for placebo.¹

cPlus BSOC.¹

3-year safety after ALSYMPCA

POST-TREATMENT, TREATMENT-RELATED HEMATOLOGIC AEs IN PATIENTS WHO ENTERED 3-YEAR, LONG-TERM SAFETY FOLLOW-UP (SAFETY POPULATION)²

Grade 3-4 hematologic AEs in the Xofigo vs placebo arm were anemia (1% vs 1%), aplastic anemia (<1% vs 0%), leukopenia (<1% vs 0%), and neutropenia (<1% vs 0%)²
Across both groups, no Grade 5 hematologic AEs were reported²
Grade 5 nonhematologic AEs included constipation, multiorgan failure, and pneumonia in the Xofigo arm (all of which were <1%)²

Limitations: assessment of long-term Xofigo safety may be difficult given that many participants were treated with other anticancer therapies in combination with Xofigo during the follow-up period. In addition, follow-up was limited to 3 years; studies with longer follow-up times are necessary to more accurately assess the long-term safety of Xofigo. AEs were reported during follow-up only if considered by the investigator to be treatment related and may therefore be underreported.²

AEs in Xofigo and placebo patients in combination with external-beam radiation therapy (EBRT) vs those without

Based on post-hoc analysis of the ALSYMPCA trial. These results are considered exploratory.

During the ALSYMPCA study, 30% (186/614) of Xofigo patients and 34% (105/307) of placebo patients received concomitant EBRT for bone pain³
At any time prior to randomization, 50% (306/614) of Xofigo patients and 49% (149/307) of placebo patients received EBRT to bone³
Within 12 weeks prior to randomization, 16% (99/614) of Xofigo patients and 16% (48/307) of placebo patients received EBRT to bone³
Patients were randomized 2:1, Xofigo: placebo³

AEs BY CONCOMITANT EBRT USE (SAFETY POPULATION, N=901^a)³

Adverse events with and without concomitant ERBT

aSafety population included all patients who received ≥1 injection of the study drug. One patient in the placebo group received 1 injection of Xofigo (week 0) and is included in the Xofigo safety analysis.

Learn About Safety After Chemotherapy

References

Xofigo^® (radium Ra 223 dichloride) injection [prescribing information]. Whippany, NJ: Bayer HealthCare Pharmaceuticals Inc.; December 2019. Return to content
Parker CC, Coleman RE, Sartor O, et al. Three-year safety of radium-223 dichloride in patients with castration-resistant prostate cancer and symptomatic bone metastases from phase 3 randomized alpharadin in symptomatic prostate cancer trial. Eur Urol. 2018;73(3):427-435. Return to content
Finkelstein SE, Michalski JM, O’Sullivan JM, Parker C, Garcia-Vargas J, Sartor O. External beam radiation therapy use and safety with radium-223 dichloride in patients with castration-resistant prostate cancer and symptomatic bone metastases from the ALSYMPCA trial. Presented at: 2015 Annual ASCO Meeting; May 29-June 2, 2015; Chicago, Illinois. Abstract 182. 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.

Safety: Overall Grade 3-4 Adverse Events

Well-documented safety profile: Overall Grade 3-4 adverse events (AEs) were similar to BSOC1

GRADE 3-4 AEs WERE REPORTED IN 57% OF XOFIGO®-TREATED PATIENTS AND 63% OF PLACEBO-TREATED PATIENTS1

ADVERSE REACTIONS OCCURRING IN ≥2% OF PATIENTS IN THE RANDOMIZED TRIAL1,a

HEMATOLOGIC LABORATORY ABNORMALITIES OCCURRING IN ≥10% OF PATIENTS1,a,b