Benefits and harms of erythropoiesis-stimulating agents for anemia related to cancer: a meta-analysis

Abstract

Background: Erythropoiesis-stimulating agents are used to treat anemia in patients with cancer. However, their safety and effectiveness is controversial. We did a systematic review of the clinical efficacy and harms of these agents in adults with anemia related to cancer or chemotherapy. Methods:We conducted a systematic review of published and unpublished randomized controlled trials (RCTs) using accepted methods for literature searches, article selection, data extraction and quality assessment. We included RCTs involving anemic adults with cancer. We compared the use of erythropoiesis-stimulating agents with nonuse and assessed clinical outcomes (all-cause mortality, cardiovascular events and hypertension, health-related quality of life, blood transfusions and tumour response) and harms (serious adverse events) between groups. Results:We identified 52 trials (n = 12 006) that met our selection criteria. The pooled all-cause mortality during treatment was significantly higher in the group receiving erythropoiesis-stimulating therapy than in the control group (relative risk [RR] 1.15, 95% confidence interval [CI] 1.03 to 1.29). Compared with no treatment, use of erythropoiesisstimulating agents led to clinically detectable improvements in disease-specific measures of quality of life. It also reduced the use of blood transfusions (RR 0.64, 95% CI 0.56 to 0.73). However, it led to an increased risk of thrombotic events (RR 1.69, 95% CI 1.27 to 2.24) and serious adverse events (RR 1.16, 95% CI 1.08 to 1.25).Interpretation: Use of erythropoiesis-stimulating agents in patients with cancer-related anemia improved some disease-specific measures of quality of life and decreased the use of blood transfusions. However, it increased the risk of death and serious adverse events. Our findings suggest that such therapy not be used routinely as an alternative to blood transfusion in patients with anemia related to cancer.

Epoetin-β treatment in patients with cancer chemotherapy-induced anaemia: the impact of initial haemoglobin and target haemoglobin levels on survival, tumour progression and thromboembolic events

“…These results are consistent both with those of a recently published, individual patient data-based meta-analysis by the Cochrane Collaboration (Bohlius et al, 2009), which showed no negative effect of epoetin therapy in patients receiving chemotherapy, and with those from a subset of patients receiving chemotherapy in a meta-analysis published by Tonelli et al (2009). In contrast to our results, however, in the overall study population of the meta-analysis published by the Cochrane Collaboration, which included patients not receiving chemotherapy, a detrimental effect on overall survival was observed.…”

AGO Recommendations for the Diagnosis and Treatment of Patients with Advanced and Metastatic Breast Cancer: Update 2018

“…Inconsist ent results were reported especially in the metastatic setting and by meta analyses [41][42][43]. In contrast, no data were avail able for the adjuvant treatment of breast cancer patients.…”

Tumor necrosis factor alpha-mediated inhibition of erythropoiesis involves GATA-1/GATA-2 balance impairment and PU.1 over-expression

“…Nevertheless, this treatment addresses only the symptoms, not the cause of the anemia. Furthermore, EPO can provoke cardiovascular and thrombo-embolic side effects, as well as possible tumor progression [21][22][23][24]. Indeed, cancer cells in many tumor types express the Erythropoietin receptor (EPOR) [25], and the interaction between Erythropoietin and the EPOR can activate the expression of genes implicated in angiogenesis -5 -hematopoietic cells independently from Erythropoietin deficiency.…”