b'When metastatic castration-resistant prostate cancer progresses on an AR pathway inhibitor ato symptomatic bone metastases with no visceral disease, 1 Choose XOFIGO to help extend survival and delay time to first to refer the patient to a nearby licensed facility tocross-functionalteamtotrainstaffonthehan-treattheirprostatecancer.Butwhenthepatientdling,administering,anddisposalofXofigo.1,2symptomatic skeletal event (SSE) with an established safety profile.You need treatment to be AGGRESSIVE, and your arrived at the CCN facility, an event triggered hisTraining for the nuclear medicine and radiation PTSD. The patient walked out without receiving oncology teams was paramount. patients want a well-established SAFETY profile. treatment. UponOS the VA, he told his SSE SAFETY1,2 returning toWorking together, the VA was licensed, conducted physician he would not go back to the CCN facilitystafftraining,certifiedtheirdosecalibrator,and at this time. received a test dose within 60 days. To ensure all XOFIGO SIGNIFICANTLY SIGNIFICANTLY IMPROVES WELL-ESTABLISHED SAFETYWhenthephysicianheardaboutthepatientsstaff were adequately trained, follow-up trainings EXTENDS OVERALL SURVIVAL MEDIAN TIME TO FIRST SSE PROFILE 1,2experience,ZablockiVAMCchiefofpharmacy,were coordinated for anyone who could not attend (OS) WITH A 30% REDUCTION BY 5.8 MONTHS 2The most common hematologicRickPurko,immediatelycontactedBayer,thethe initial training session.IN DEATH VS PLACEBO 2Secondary endst two edianthse t laboratory abnormalities in the Xofigomaker of Xofigo, to see what could be done to helpIn jupoint: mmon tim, tohe Bayer and local VA team arm (10%) vs the placebo arm (all Median OS was 14.0 months (9 require contract first SSE with Xofigo + BSOC was grades [%]), respectively, were anemiathis Veteran. Ultimately this would5% CI: 12.1- completed this multi-step process, knowing that execution, certification of the VAMC tore 15.6 months vs BSOC at 9.8 months 2 (93% vs 88%), lymphocytopenia (72%radium Ra 223 dichloride 15.8) for Xofigo + best standard of ca receive anda Veteran was awaiting his treatment. For Bayer, (BSOC) vs 11.2 months for placebo + BSOC (HR=0.66 [95% CI: 0.52-0.83],P0.001) vs 53%), leukopenia (35% vs 10%),INJECTION administer Xofigo, and training for staffa processpatients always come first. But the situation also (95% CI: 9.0-13.2). Hazard ratio (HR)=0.695The majority of events consisted of EBRTwhich normally takes up to three months.highlightedanotherreality:Whilecontrolsare thrombocytopenia (31% vs 22%), and(95% CI: 0.552-0.875) P=0.00185 1 to bone metastases 1 1TheChiefofMedicineatZablockiVAMC,necessarytoguaranteetherightproduct(18% vs 5%)neutropenia getsEvaluated in the ALSYMPCA trial:SSE defined as EBRT to relieve skeletalDr.AndreeaAnton,coordinatedwiththelocalto the right patient at the right time and place, double-blind, randomized, placebo- symptoms, new symptomatic pathologicThe most common nonhematologicRadiationOncology(Dr.ElizabethGore),they should not become barriersadvers h pr ct vent controlled, phase III study of 921 patients bone fracture, occurrence of spinal cord whic e rea e ions in the Xofigo arm (10%)with castration-resistant prostate cancer compression, and tumor-related orthopedic vs the placebo arm, respectively, wereMedical Oncology, and Nuclear Medicine teamsVeterans from receiving the best potential medi-to arrange a training for necessary staff and com- cal care available.nausea (36% vs 35%), diarrhea (25%with symptomatic bone metastases and surgical intervention 2 vs 15%), vomiting (19% vs 14%), andplete the budgeting process. Bayer worked with no known visceral metastatic disease 1,2 peripheral edema (13% vs 10%) 1administrativestafftofinalizetheVAcontractPlease see additional Important Safety InformationIn ALSYMPCA, BSOC was defined asforms necessary to establish an appropriate bud- below. antiandrogens, local external-beamget for treatment he Iny (EBRT), l, Bayerole, a radiation t .rap paralleketoconaz activated estrogens, estramustine, or treatmentwith glucocorticoids 2abirateroneacetateplusprednisone/prednisoloneAdverseReactions:Themostcommonadverse comparedtopatientswhoreceivedplaceboinreactions (10%) in the Xofigo arm vs the placebo arm, AR=Androgen Receptor; CI=Confidence Interval. combination with abiraterone acetate plus prednisone/ respectively, were nausea (36% vs 35%), diarrhea (25% aIn ALSYMPCA, BSOC was defined as antiandrogens, EBRT, ketoconazole, estramustine, or treatment with glucocorticoids.2 prednisolone. Safety and efficacy with the combinationvs 15%), vomiting (19% vs 14%), and peripheral edema of Xofigo and agents other than gonadotropin-releasing(13%vs10%).Grade3and4adverseeventswere XOFIGO IS INDICATED for the treatment of patients with castration-resistant prostate cancer (CRPC), symptomatic bone metastases and no knownhormone analogues have not been established reported in 57% of Xofigo-treated patients and 63% of visceral metastatic disease. placebo-treated patients. The most common hematologicEmbryo-FetalToxicity:Thesafetyandefficacyof laboratory abnormalities in the Xofigo arm (10%) vs theHematological Evaluation: Monitor blood counts at baseline and prior with abiraterone acetate plus prednisone/prednisolone compared to such as urine, feces, or vomit.Therefore, radiation protection precautionsIMPORTANT SAFETY INFORMATION Xofigo have not been established in females. Xofigoplacebo arm, respectively, were anemia (93% vs 88%), to every dose of Xofigo. Prior to first administering Xofigo, the absolute patients who received placebo in combination with abiraterone acetate must be taken in accordance with national and local regulationscan cause fetal harm when administered to a pregnantlymphocytopenia(72%vs53%),leukopenia(35%vs Warnings and Precautions: neutrophil count (ANC) should be 1.510 9 /L, the platelet count 100 plus prednisone/prednisolone. Safety and efficacy with the combinationfemale.AdvisepregnantfemalesandfemalesofAdverse Reactions: The most common adverse reactions (10%) in10%), thrombocytopenia (31% vs 22%), and neutropeniaBone Marrow Suppression: In the phase 3 ALSYMPCA trial, 2% of10 9 /L, and hemoglobin 10 g/dL. Prior to subsequent administrations, reproductive potentialothe potentialadotropin-releasinghormoneofXofigoandagents of therthangon risk to a fetus.(18% vs 5%) the Xofigo arm vs the placebo arm, respectively, were nausea (36% vspatients in the Xofigo arm experienced bone marrow failure or ongoing the ANC should be 110 9 /L and the platelet count 5010 9 /L. Adviseues have not beeuse condoms and their female analog male patients to n established 35%), diarrhea (25% vs 15%), vomiting (19% vs 14%), and peripheralpancytopenia, compared to no patients treated with placebo.There were Discontinue Xofigo if hematologic values do not recover within 6 to 8 partnersofreproductivepotentialtouseeffectiveEmbryo-Fetal Toxicity: The safety and efficacy of Xofigo have not edema (13% vs 10%). Grade 3 and 4 adverse events were reported intwo deaths due to bone marrow failure. For 7 of 13 patients treated with weeks after the last administration despite receiving supportive care contraception during and for 6 months after completing Xofigo bone marrow failure was ongoing at the time of death.Among beenestablishedinfemales.Xofigocancausefetalharmwhen 57% of Xofigo-treated patients and 63% of placebo-treated patients.treatment with Xofigo ConcomitantUseWithChemotherapy:Safetyandefficacyof administered to a pregnant female. Advise pregnant females and The most common hematologic laboratory abnormalities in the Xofigothe 13 patients who experienced bone marrow failure, 54% required concomitant chemotherapy with Xofigo have not been established. females of reproductive potential of the potential risk to a fetus.Advise arm (10%) vs the placebo arm, respectively, were anemia (93% vsblood transfusions. Four percent (4%) of patients in the Xofigo arm AdministrationandRadiationProtection:Xofigo Outside of a clinical trial, concomitant use of Xofigo in patients on male patients to use condoms and their female partners of reproductive 88%),lymphocytopenia(72%vs53%),leukopenia(35%vs10%),and 2% in the placebo arm permanently discontinued therapy due shouldbereceived,used,andadministeredonlyby chemotherapy is not recommended due to the potential for additive authorizedpersons intive contrace clinical settings.for 6 months after thrombocytopenia (31% vs 22%), and neutropenia (18% vs 5%)to bone marrow suppression. In the randomized trial, deaths related potential to use effec designatedption during andThe myelosuppression. If chemotherapy, other systemic radioisotopes, or administrationreatment with Xofigo withpotential completing t ofXofigoisassociatedto vascular hemorrhage in association with myelosuppression were hemibody external radiotherapy are administered during the treatment risks to other persons from radiation or contamination Administration and Radiation Protection: Xofigo should be received,observed in 1% of Xofigo-treated patients compared to 0.3% of patients period, Xofigo should be discontinued from spills of bodily fluids such as urine, feces, or vomit. used, and administered only by authorized persons in designated clinicaltreated with placebo. The incidence of infection-related deaths (2%), Therefore, radiation protection precautions must be takenIncreased Fractures and Mortality in Combination With Abiraterone settings.The administration of Xofigo is associated with potential risks toserious infections (10%), and febrile neutropenia (1%) was similar for in accordance with national and local regulationspatients treated with Xofigo and placebo. Myelosuppressionnotably Plus Prednisone/Prednisolone: Xofigo is not recommended for use other persons from radiation or contamination from spills of bodily fluids For additional risk and important use information, please in combination with abiraterone acetate plus prednisone/prednisolone References: 1. Xofigo(radium Ra 223 dichloride) injection [prescribing information].thrombocytopenia,neutropenia,pancytopenia,andleukopeniahas outside of clinical trials. At the primary analysis of the phase 3 ERA- see the Full Prescribing Information. Whippany, NJ: Bayer Healthcare Pharmaceuticals Inc.; December 2019. 2. Parker C,been reported in patients treated with Xofigo. 223 study that evaluated concurrent initiation of Xofigo in combination Nilsson S,Heinrich D,et al.Alpha emitter radium-223 and survival in metastatic prostate Monitor patients with evidence of compromised bone marrow reserve cancer.N Engl J Med.2013;369(3):213-223.closely and provide supportive care measures when clinically indicated. withabirateroneacetateplusprednisone/prednisolonein806asymptomatic or mildly symptomatic mCRPC patients, an increased2020 Bayer. All rights reserved. You are encouraged to report side effects or quality DiscontinueXofigoinpatientswhoexperiencelife-threatening incidence of fractures (28.6% vs 11.4%) and deaths (38.5% vs 35.5%) BAYER, the Bayer Cross, and Xofigo are registered trademarks of Bayer. Please see the following pages for brief summary of fullcomplaints of the products to the FDA by visitingcomplications despite supportive care for bone marrow failure MAC-XOF-US-0107-1 01/21 Printed in USA www.fda.gov/medwatch , or call 1-800-FDA-1088.have been observed in patients who received Xofigo in combination PP-XOF-US-1081-103/20Prescribing Information.'