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Methods: We conducted a systematic review of published and unpublished randomized controlled trials (RCTs) using accepted methods for literature searches, article selection, data extraction and quality assessment.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 erythropoiesis-stimulating 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.

Figure 1

Selection of studies for inclusion in the meta-analysis. RCT = randomized controlled trial.

Figure 2

Effect of treatment with erythropoiesis-stimulating agents versus no treatment on all-cause mortality. CI = confidence interval. The letters X and Y following study names are indicated for studies with more than one treatment arm.

Figure 3

Effect of treatment with erythropoiesis-stimulating agents versus no treatment on change in quality of life. FACT = Functional Assessment of Cancer Therapy, SD = standard deviation, CI = confidence interval.

Figure 4

Effect of treatment with erythropoiesis-stimulating agents versus no treatment on blood transfusions. CI = confidence interval. The letters W, X, Y and Z following study names are indicated for studies with more than one treatment arm.

Figure 5

Effect of treatment with erythropoiesis-stimulating agents versus no treatment on serious adverse events. CI = confidence interval. The letters X and Y following study names are indicated for studies with more than one treatment arm.