VTE and mortality risks found with erythropoiesis-stimulating agents

Administration of erythropoiesis-stimulating agents increases the risk for venous thromboembolism and mortality in patients with anemia of cancer, according to data from a recent meta-analysis.

Researchers from Northwestern University evaluated data from 38 phase-3 trials included in a Cochrane overview and 13 additional phase-3 trials. They analyzed survival in 13,611 patients in all 51 trials.

For patients with cancer who were treated with ESAs, the hazard ratio for mortality was 1.10 (95% CI, 1.01-1.20), which was higher than among control patients.

VTE was evaluated among 8,172 patients in 38 trials. The risk for VTE was 1.57-fold higher in patients who received ESAs (334 events among 4,610 patients treated with ESAs, compared with 173 events in 3,562 control patients).

“These risks are important, given the prevalence of ESA use as a supportive care drug among patients with cancer as well as the dissemination of a series of safety advisories by the FDA and ESA manufacturers,” the researchers wrote.

The researchers also performed subgroup analyses of 45 trials in which patients were treated for anemia related to chemotherapy or radiation therapy and of six trials that included patients who were not receiving any therapy. There was a significant increase in mortality in the subgroup of patients who were not receiving therapy. Patients who received ESAs that were receiving therapy had a nonsignificant increase in mortality. – by Emily Shafer

JAMA. 2008;299:914-924.

One of the differences of this analysis compared with previous meta-analyses is that this analysis included studies where VTE and mortality risks were not primary or secondary endpoints. The studies included data on these risks, but neither risk was a study endpoint. This meta-analysis shows an increased VTE risk and a 10% increase in mortality. What we don’t know is why the mortality is different. It may be due to thromboembolic phenomenon, or it may be due to cancer progression. This analysis adds another layer to the evidence that these risks exist. Physicians need to discuss the relative risk of these drugs with patients and talk about the alternatives, such as transfusions, which carry their own risks.

– Samuel Silver, MD, PhD

HemOnc Today Section Editor, Policy, Patient and Practice Issues