Erythropoiesis-Stimulating Agents Sometimes Appropriate for Cancer-Associated Anemia

By Will Boggs MD

June 03, 2019

NEW YORK (Reuters Health) - Erythropoiesis-stimulating agents (ESAs) may be appropriate for treating cancer-associated anemia in patients whose cancer treatment is not curative in intent, according to updated guidelines.

"Use of ESAs should be considered very carefully, weighing benefits versus risk and in conjunction with patients' input and preferences," Dr. Alejandro Lazo-Langner from Western University, in London, Canada, told Reuters Health by email. "Emphasis should be made on their use only for patients with chemotherapy-associated anemia on palliative chemotherapy in order to reduce transfusions."

ESAs raise hemoglobin levels and reduce the need for red blood cell (RBC) transfusions but increase the risk of thromboembolic events, Dr. Lazo-Langner and colleagues point out in a clinical practice guideline update from the American Society of Clinical Oncology/American Society of Hematology (ASCO/ASH). Some studies have suggested that the agents might also decrease survival and/or increase the risk of cancer progression or recurrence in patients with cancer.

Dr. Lazo-Langner and a multidisciplinary expert panel used a systematic review of the literature from 2010 to 2018 and clinical experience to develop recommendations that addressed 10 clinical questions.

The foremost recommendation addresses the appropriate population for ESA treatment: depending on clinical circumstances, ESAs may be offered to patients with chemotherapy-associated anemia whose cancer treatment is not curative in intent and whose hemoglobin has declined to <10 g/dL.

The drugs should not be offered to patients with chemotherapy-associated anemia whose cancer treatment is curative in intent.

ESA treatment is not appropriate for most patients with non-chemotherapy-associated anemia, although ESAs may be offered to patients with lower-risk myelodysplastic syndromes and a serum erythropoietin level of 500 IU/L or lower.

The expert panel considers epoetin beta and alfa, darbepoetin and biosimilar epoetin alfa to have equivalent effectiveness and safety.

The guideline notes that ESAs increase the risk of thromboembolism, so clinicians should carefully weigh the risks of thromboembolism and use caution and clinical judgment when considering use of these agents.

U.S. Food and Drug Administration guidelines should be followed for starting and modifying doses of ESAs, and the target hemoglobin should be the lowest concentration needed to avoid or reduce the need for RBC transfusions.

ESAs should be discontinued in patients who do not respond within six to eight weeks.

All 10 recommendations and their supporting evidence are detailed in the Journal of Clinical Oncology, online April 10.

Dr. Sandro Barni from the Medical Oncology Unit, in Treviglio, Italy, who recently co-authored a position paper on management of iron deficiency in adult cancer patients, told Reuters Health by email, "We need to understand anemia associated with targeted therapy (e.g., tyrosine kinase inhibitors (TKI)) or immune-checkpoint inhibitors."

He added that the new guidelines also have no mention of whether and how ESAs might be used before chemotherapy in anemic patients, and he emphasized that "iron replacement may be used to improve hemoglobin response and reduce red blood cell transfusions for patients with iron deficiency receiving ESAs." Dr. Barni was not involved in the new work.

Dr. H. Tilman Steinmetz from Oncology Outpatient Clinic in Cologne, Germany, who studies anemia in cancer patients and also was not involved in the guideline development, told Reuters Health by email, "Chemotherapy itself is only a minor cause of anemia in cancer patients. The term chemotherapy-induced or -associated anemia came up with the studies of the ESA-pharmaceutical industry, who performed high-quality RCTs to get an approval or a better position of their drugs."

"A RCT with the primary aim to look for the best treatment of anemia in cancer, guided by a careful diagnostic procedure for the cause of anemia, was never done," he said. "This Guideline update only looked for RCTs or meta-analyses of RCTs and only asked questions that could be answered by the mainly industry-sponsored studies."

"I think we unfortunately (don't have) enough clinically driven research compared to the power of the industry, who wants to approve drugs," Dr. Steinmetz said. "I'm sure that ESAs will still play an important role in the future, together with intravenous iron, in the treatment of cancer-associated anemia, especially caused by an inflammatory reaction."


J Clin Oncol 2019.