Erythropoietin Stimulating Agents (ESAs): Reassessment of Use in Cancer and Chronic Kidney Disease (CKD) Settings in the United States, Canada, and Europe.

Abstract

Abstract 4538 IntroductionInternational reassessments of erythropoiesis stimulating agents (ESAs) for anemia have recently occurred. While ESAs prevent blood transfusions and, improve select quality of life domains among chronic kidney disease (CKD) patients, 8 trials individually identified increased mortality and/or tumor progression among cancer patients treated with ESAs. For CKD, one study of non-dialysis CKD patients targeted to higher versus lower hemoglobin (Hb) levels identified 34% increased relative risk (17.5% vs. 13.5%) for death, acute myocardial infarction, congestive heart failure hospitalization, or stroke with a higher Hb target. MethodsGuidelines, notifications from regulatory agencies and manufacturers, reimbursement policies, and utilization for ESAs in the cancer and CKD settings within the U.S., Europe, and Canada were reviewed. Results: Cancer SettingIn 2008, the Food and Drug Administration (FDA) restricted ESAs from cancer patients seeking cure. Reimbursement is limited to Hb levels < 10 g/dL. In the U.S., ESA usage increased 340% between 2001 and 2006, and decreased 60% since 2007. The European Medicines Agency (EMEA) reports that ESA benefits do not outweigh risks. In Europe, ESA reimbursement is included in global provider payments. Between 2001 and 2006, ESA use increased 51%; since 2006, use has decreased 10%. Canadian manufacturers recommend ESA usage based on patient preference. In Canada, reimbursement for myelosuppressive chemotherapy with ESAs is restricted to Hb levels of 10-11 g/dL in Alberta and 11-12.5 g/dL in British Columbia. Usage increased 20% between 2004 and 2007. CKD SettingThe FDA recommends Hb levels < 12 g/dL and Medicare reimbursement is restricted to Hb levels ≥ 13 g/dL. Between 2001 and 2006, usage increased 480% (non-dialysis) and 40% (dialysis) in the U.S. Since 2007, ESA use has decreased 30% (non-dialysis) and 17% (dialysis). The EMEA recommends target Hb levels of 10-12 g/dL. In Europe, ESA usage has increased 10% since 2001. The 2009 Canadian label recommends Hb levels < 12 g/dL. Within Canada, ESA usage increased 30% since 2004. ConclusionsWhile reassessments of ESA safety have occurred internationally, safety concerns in the U.S. have resulted in marked decrements in ESA use among cancer and CKD patients, whereas in Europe and Canada ESA use has increased over time.SettingUnited StatesEuropeCanadaCancerCKDCancerCKDCancerCKDGuideline2009:-ESAs indicated to prevent transfusions-ESAs may reduce fatigue-ESAs should not be administered to cancer patients seeking cure2007:-Patients should consider potential benefits and harms of ESAs-Target Hb levels: 11-12 g/dL, not >13 g/dL2007:-Consider ESA use in asymptomatic chemotherapy patients with Hb levels 11-11.9g/dL-Initiate ESA use in symptomatic anemic chemotherapy patients with Hb levels 9-11g/dL2009:-Hb levels should be maintained at 11-12g/dL, not >13g/dL2008:-Achieved Hb levels should be <12g/dL-Target Hb levels >12g/dL associated with higher risks of serious cardiovascular events and death2009:-Target Hb levels: 10-12 g/dLPackage Insert2008:-ESAs should not be administered to cancer patients seeking cure-Risk Evaluation and Management Systems for ESAs should include patient guide warning of increased tumor progression and death risks in chemotherapy patients-Removed text indicating ESA treatment is safe at Hb levels ≥ 12g/dL2008:-ESAs indicated for treatment of symptomatic anemic patients with chronic renal failure-Target Hblevels: 10-12g/dL, not >12g/dL2008:-ESAs indicated for treatment of symptomatic anemic patients receiving chemotherapy-ESAs may affect erythropoietin receptors on tumor cells, promoting tumors and accelerating mortality2008:-ESAs indicated for treatment of symptomatic anemic CKD patients with target Hb levels 10-12g/dL2009:-ESAs indicated for treatment of chemotherapy-associated anemia-Increased mortality risks with ESA administration to cancer patients with Hb levels >12 g/dL.- Patients with chemotherapy-associated anemia and reasonably long life expectancies should consider ESA risks and benefits and personal preferences.–Transfusions preferred in patients with long life expectancies receiving myelosuppressive chemotherapy2009:-ESAs indicated in treatment of anemia associated with chronic renal failure for dialysis and non-dialysis patients-Target Hb levels: 10-12g/dL Disclosures:No relevant conflicts of interest to declare.