Researchers affiliated with the EPO IPD Meta-Analysis Collaborative Group have reported that erythropoiesis-stimulatin agents (ESAs), such as Epogen® (epoetin alfa) and darbebpoetin (Aranesp®), increase on-study mortality by 17% and decease overall survival by 6% compared with control patients. The details of this study were presented at the annual meeting of the American Society Hematology on December 6, 2008 in San Francisco.[1] 

Recent concerns have been raised over the possibility that ESAs can increase the relapse rates and increase the incidence of venous thromboembolism (VTE) in patients with cancer. The increased incidence of VTE with use of ESAs is fairly well documented, but most studies have shown no impact of ESAs on overall survival.

A previous report from the EPO IPD Meta-Analysis Collaborative Group was published in the February 27, 2008 issue of the Journal of the American Medical Association. This study showed that the use of ESAs administered to patients with cancer-related anemia was associated with a 57% increase in the incidence of venous-thromboembolism (VTE) and a 10% increase in mortality from all causes. This study looked at 51 randomized clinical trials evaluating ESAs versus a placebo in patients with cancer-related anemia (n=2,089) or treatment-related anemia(n=11,522). Survival was evaluated in 13,611 patients in 51 Phase III trials. There was a 10% increase in mortality in patients receiving ESAs compared with control patients. The relative risk for mortality in cancer-related anemia was 1.19 versus 1.09 for patients with treatment-related anemia.  VTE was evaluated in 38 of the 51 trials involving 8,172 patients. Patients receiving ESAs had a 57% increase in VTE compared with placebo recipients.

The study presented at ASH included data from 13,933 cancer patients enrolled in 53 randomized studies. These authors looked at on-study mortality defined as events occurring during or 28 days after the end of the study. Overall survival included all available follow-up from the previous report. These authors reported that ESAs increased on-study mortality by 17% and decreased overall survival by 6%. In the approximately 10,000 patients receiving chemotherapy, on-study mortality was increased by 10% and overall survival was decreased by 4%.  These authors also reported that these adverse effects on on-study mortality and overall survival were not affected by any variable such as age, sex, hemoglobin levels etc. They concluded: “In clinical practice, risks of ESAs must be balanced against benefits of ESAs depending on clinical circumstances of the individual patient.”

Comments: These findings raise concern about the safety of ESAs in patients with cancer and the potential of these agents for increasing mortality. Physicians should be aware of the new guidelines for the use of ESAs in cancer patients.

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