FDA committee recommends restrictions on use of anemia drugs during chemotherapy

In a meeting on March 13, 2008 the Oncologic Drugs Advisory Committee (ODAC) of the FDA recommended further restrictions in the use of erythropoiesis-stimulating agents or ESAs to treat chemotherapy-induced anemia.  The drugs, marketed as Aranesp®, Epogen®,and Procrit®, are given to prevent blood transfusions during chemotherapy.

While the committee did not recommend completely ending prescribing ESAs for cancer patients, they did ask that use be limited:

• They voted 13 to 1 that ESAs remain available to some cancer patients.
• By a vote of 9 to 5, the panel said that ESAs should not be used by patients with breast or head and neck cancer, where evidence is strongest that the drugs may shorten survival.
• In a vote of 11 to 2, with 1 abstaining, they recommended that ESAs not be used when patients were being treated with the goal of curing their cancer but be limited to treatment of advanced stage disease.
• They urged that patient sign an informed consent before they were given ESAs helping them to understand the potential risks.

The ODAC recommendations are included in an article in the New York Times that also has statements made during the meeting by Carlea Bauman, C3:Colorectal Cancer Coalition President, and Robert Erwin, a member of the C3 Board of Directors.

Carlea Bauman, President of C3:Colorectal Cancer Coalition, told the panel,

There is a perceived lack of progress. The drugs have been on the market for many years, billions of dollars have been spent by insurers, millions of patients have been treated, and yet we still have many of the same unanswered questions.

C3 recommended establishing a registry of patients who were taking the drugs so that information could be collected and analyzed about ESA risks and benefits.

Background information on the studies that ODAC considered in preparation for yesterday’s meeting is included in an FDA Briefing Document.  From that document:

Whereas at the time of approval, safety concerns were theoretical, there is now mounting evidence of documented effects on survival, tumor progression, and thrombotic events which require a re-assessment of the net benefits of this class of drugs. With the results of two additional clinical studies with evidence of harmful effects (a total of eight studies as of this date), FDA requests the Committee’s advice with regards to appropriate actions to be taken at this time.

Prior to the meeting, Amgen who manufactures the ESA drugs under consideration issued this statement. They wrote,

Amgen strongly believes that ESAs provide an important clinical option for some patients, and looks forward to collaborating with the ODAC and FDA to maximize the benefits of these drugs when used according to the approved labeling while minimizing the risks.

The ODAC meeting was prompted by information from eight different studies that showed poorer outcomes for cancer patients who received an erythropoiesis-stimulating drug rather than a placebo to treat anemia.  There was evidence that ESAs might be responsible for poorer survival, additional blood clots, or growth of tumors.

Since the studies were exploring new uses of the drugs beyond the limits on the approved FDA label, safety issues for labeled uses were not clear.  Many questions about safe use of ESAs for cancer patients receiving chemotherapy remain.

In November of 2007, the FDA revised labeling for Procrit, Aranesp, and Epogen to reflect research that found anemic patients not on chemotherapy had reduced survival when given the drugs.  The new label included black box warnings:

• Not to target hemoglobin levels at or above 12 g/dL.
• Risks of shortened survival and tumor progression have not been excluded at target hemoglobins below 12 g/dL
• Use the lowest dose possible to avoid blood transfusion
• Use only for chemotherapy-induced anemia, not for anemia in cancer patients who are not receiving chemotherapy.
• Stop ESAs when chemotherapy ends

The March 18 ODAC recommendations must be acted on by the FDA before more labeling changes are made, but their opinions are usually taken very seriously.

What does this mean for patients?

If you are anemic and on chemotherapy, discuss using an erythropoiesis-stimulating agent (ESA) such as Procrit, Aranesp, or Epogen very carefully with your doctor.

• You should not take an ESA to treat cancer anemia if you are not on chemotherapy.  (On the FDA approved label)
• There is no evidence that an ESA will make you feel better or improve your quality of life.
• The goal of using an ESA is to reduce the risk of needing a blood transfusion, but you may still need one even if you take an ESA.
• Ask that the lowest dose possible be used to slowly raise hemoglobin levels. (On the FDA approved label)
• Stop ESAs when you stop chemotherapy.

While the latest ODAC recommendations are not yet part of the FDA labeling for Procrit, Aranesp, or Epogen, you should also discuss them with your doctor including:

• Not taking an ESA if you have breast cancer or head and neck cancer.
• Not using an ESA for cancer treatments that are focused on cure such as adjuvant treatment after surgery for cancer that has not yet spread.

ODAC has recommended that patients and doctors discuss the risks and benefits of ESA use together.  You may be asked to sign an informed consent before being treated with one.  Read it carefully, discuss it with your doctors and your family, and make your own decision.

Disclosure:  C3 believes in fully disclosing sources of financial support. In 2006 and 2007, C3 received funding from Amgen in the form of a charitable donation. Johnson & Johnson held a meeting in February 2008 in Washington, DC, and paid the travel expenses of a C3 Board member. Neither of these companies nor any of our other corporate supporters have influenced our comments on this issue.