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FDA Updates Warning Labels of ESAs in Cancer Patients

FDA Updates Warning Labels of ESAs in Cancer Patients

ROCKVILLE, Maryland—FDA has issued a black box warning against using higher than necessary doses of erythropoiesis-stimulating agents (ESAs). The agency ordered several labeling changes after receiving additional safety data from studies showing serious adverse effects related to the use of Aranesp (darbepoetin alfa, Amgen) and Epogen and Procrit (epoetin alfa, Amgen and Ortho Biotech).

The black box warning cautions physicians to use the lowest dose of an ESA needed to gradually increase hemoglobin to the lowest level sufficient to avoid transfusions. FDA emphasized that ESAs are not indicated for cancer patients who are not receiving chemotherapy or radiation therapy, as they increase mortality in these patients when administered to target a hemoglobin level of 12 g/dL. [See ONI February 2007, page 27.]

The agency also reminded physicians that ESAs are approved only to reduce the need for red blood cell transfusions. "These products have not been shown to improve or relieve the symptoms of anemia, or to improve quality of life in patients with cancer," FDA said. The black box warning states that ESAs increased the risk of death and serious cardiovascular events when administered to target a hemoglobin level higher than 12 g/dL.

The warning and other labeling changes flowed from several studies that will be discussed at the May 10 Oncology Drugs Advisory Committee (ODAC) meeting to re-evaluate the safety and dosing of ESAs in cancer patients. Soon after FDA revealed the new labeling, the Centers for Medicare and Medicaid Services ordered a review of all Medicare policies related to the use of ESAs.

In its announcement, FDA briefly described findings from six of the studies that led to the updated warning.

•In DAHANCA 10, a randomized study in 522 patients with advanced head and neck cancer treated with radiation therapy, an interim analysis of 484 patients found a significant 10% increase in the locoregional failure rate among patients treated with darbepoetin, compared with placebo. Patients who received darbepoetin to raise hemoglobin to greater than 12 g/dL had a shorter time to progression, compared with placebo.

•Epoetin was associated with a shortened overall survival rate and an increased death rate attributed to disease progression at 4 months in the randomized BEST study of 939 women with metastatic breast cancer undergoing chemotherapy who received the ESA to maintain a hemoglobin count of 12 to 14 g/dL. Researchers ended the trial prematurely because of higher mortality in the epoetin-treated women vs placebo (8.7% vs 3.4%) and a higher fatal thrombotic event rate (1.1% vs 0.2%). At study termination, 12-month overall survival was lower in the epoetin patients (70% vs 76%).

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