FDA REQUIRES SPECIAL ONCOLOGIST TRAINING FOR ESAs USE

February 16, 2010 — Oncologists who treat cancer patients with erythropoiesis-stimulating agents (ESAs) made by Amgen must receive extra training on administering the drugs as well tell patients about the drugs' risks, benefits, and permitted uses under a safety program announced today by the US Food and Drug Administration (FDA).

The new program is based on multiple studies showing that ESAs cause tumors to grow faster and sometimes lead to earlier deaths in cancer patients, said Richard Pazdur, MD, director of the Office of Oncology Drug Products in the FDA's Center for Drug Evaluation and Research (CDER), at a press conference today.

A large meta-analysis of cancer patients published in The Lancet last year, and covered by Medscape Oncology at the time, demonstrated that ESAs increased the relative risk for mortality by 17%. For cancer patients undergoing chemotherapy, the relative risk for mortality increased by 10%.

Clinicians prescribe ESAs to treat anemia, which can result from chemotherapy among other reasons. ESAs, a form of the human protein erythropoietin, stimulate bone marrow to manufacture red blood cells. The FDA has approved ESAs to treat anemia in patients receiving chemotherapy as well as patients with chronic kidney disease and HIV infection treated with zidovudine.

Amgen makes ESAs marketed as Epogen (epoetin alfa), Procrit (epoetin alfa; marketed by Centocor Ortho Biotech), and Aranesp (darbepoetin alfa). These agents now bear black-box warnings that state they can increase the risk for death in cancer patients.

To Prescribe ESAs, Oncologists Must Complete Training Module

In light of the published research about the increased mortality risk for cancer patients taking ESAs, the FDA ordered Amgen in 2008 to develop a risk management program for the drugs. Under the program, called a risk evaluation and mitigation strategy, clinicians must provide patients — no matter why they have been prescribed an ESA — with a medication guide instructing them on how to safely take the drug. These patients must be warned that ESAs increase the risk for stroke, heart attack, heart failure, blood clots, and death, Dr. Pazdur said.

A subsection of the risk evaluation and mitigation strategy program called Assisting Providers and Cancers Patients With Risk Information for the Safe Use of ESAs (APPRISE) has more stringent requirements. To be enrolled in APPRISE, oncologists treating cancer patients with ESAs must complete a special training module on using ESAs, followed by certification. Plus, they must re-enroll in APPRISE every 3 years. Oncologists who are not enrolled will not be able to prescribe the drugs for cancer patients.

They also must discuss with cancer patients the risks, benefits, and FDA-approved uses of ESAs and document this discussion by obtaining the patient's signature.

Dr. Pazdur said the risk-benefit analysis for ESAs is different for cancer patients receiving chemotherapy for curative purposes compared with those receiving it for palliative purposes. "If you're treating someone for cure, you don't want to reduce the chances for cure," he said.

Oncologists Will Have 1 Year to Enroll in FDA-Required Training Before Restrictions Take Effect

The APPRISE program launches March 24. Physicians and hospitals will have 1 year to enroll in APPRISE before Amgen begins restricting distribution of ESAs to anyone who is not enrolled, according to Patricia Keegan, MD, director of the CDER's Division of Biologic Oncology Products. Until then, physicians and hospitals are still free to dispense the drugs, said Dr. Keegan. Most cancer patients treated with ESAs obtain them from an oncologist's office, a hospital, or a hospital outpatient clinic, as opposed to a retail pharmacy.

"Many oncologists prescribe and dispense," noted Jeff Summers, MD, deputy director for safety at CDER's Division of Biologic Oncology Products, at the press conference. "So there is some conflict of interest."

Dr. Pazdur said that the FDA did not want the new safety program to "interfere in a draconian fashion with the practice of medicine."

"We know it will create new responsibilities for busy physicians," he said. "But by requiring additional education for healthcare providers and by ensuring patients have drug-risk information, we can help patients make the best choices."

More information is available on the FDA's MedWatch Web site.