Erythropoiesis-Stimulating Agents in the Management of Anemia in Chronic Kidney Disease or Cancer: A Historical Perspective.

George M. Rodgers,Matti Aapro,Luiz H. Arantes,Jay Wish,Selwyn Fung,Kashyap Patel,Pere Gascón

doi:10.3389/fphar.2018.01498

Abstract

Anemia is common in patients with cancer or with chronic kidney disease (CKD). Although the introduction of erythropoiesis-stimulating agents (ESAs) has transformed the management of anemia, their use has been complicated by a number of factors including frequent guideline updates, safety concerns and, in the United States, a Risk Evaluation and Mitigation Strategy (REMS) program, which aimed to ensure that the benefits of ESAs outweigh the risks. Many previous concerns around ESA use in cancer and CKD have been addressed by the reassuring results of post-approval studies, and biosimilar ESAs have been used in Europe for many years, with safety and efficacy profiles similar to originator products. This review describes the evolution of the use of ESAs from approval to the present day, discussing results from clinical studies of ESAs in cancer and CKD, and the influence of these findings on product labeling and guideline updates. We also discuss the impact of the introduction of ESA biosimilars in Europe, bringing cost savings and increased access to patients.

Highlights

Over 100 years ago, Carnot and Deflandre speculated on the existence of a humoral factor produced in response to anemia
Nagel et al (2011): randomized Phase 2 study involving chemotherapy in limited or extensive SCLC with or without darbepoetin; no differences in progression-free survival (PFS) or 1-year survival rates reported between treatment arms
Fujisaka et al (2011): randomized Phase 3 trial of epoetin beta in patients receiving chemotherapy for lung/gynecological cancer; no difference in 1-year survival rates reported between erythropoiesis-stimulating agent (ESA) treated vs. untreated

Summary

Introduction

Over 100 years ago, Carnot and Deflandre speculated on the existence of a humoral factor produced in response to anemia. In 2004, the EORTC published guidelines for ESA use in anemic patients with cancer, which reported a slight elevation in the risk of thromboembolic events and hypertension in patients with CIA receiving ESAs (Bokemeyer et al, 2004).

Results

Conclusion