Sides dig in as ESA policy debate heats up

The controversial new Medicare policy restricting the use of erythropoiesis-stimulating agents (ESAs)—Medicare's single largest drug expense—continues to stir intense debate. Unless the Centers for Medicare and Medicaid Services responds to the oncology community's pleas to change the current policy, the only alternative may be legislative intervention.

Prompted by safety concerns, FDA and CMS have joined forces in the battle over the "proper" use of ESAs in oncology. The two agencies contend that the new CMS national coverage decision (NCD) is backed by sound scientific data, while the oncology community argues that the policy is too restrictive and stems as much from economic concerns as from concerns about patient safety.

Fearing a return to the "dark ages" when transfusions were the primary option for treating anemic cancer patients, oncology leaders are committed to reversing the NCD, Joseph S. Bailes, MD, chair of ASCO's Government Relations Council, told Oncology NEWS International.

"The new restrictions are inconsistent with both FDA-approved labeling and national guidelines, and we strongly disagree with this restriction," Dr. Bailes said. Although the new Medicare coverage determination has attracted congressional attention, Dr. Bailes conceded that given the current political climate, reversing the NCD will be a long uphill battle.

Safety concerns escalate

Safety concerns about ESAs were first raised in 2003 by two studies that some experts say were flawed and unconvincing. Since then, subsequent trials have produced equally debatable conclusions.

On March 9, 2007, based largely on the results of a phase III trial called the "103 study" and some preliminary data from a Danish trial called DAHANCA 10, FDA added a new "black box" warning to the package inserts of ESAs marketed in the United States. The new label recommended using the lowest ESA dose necessary to avoid the need for blood transfusions.

The warning label prompted the new CMS directive: In cancer patients with chemotherapy-related anemia, ESAs cannot be used until the patient's hemoglobin level falls below 10 g/dL and must be stopped if, after 4 weeks of therapy, the hemoglobin level rises to 10 g/dL or higher. Starting January 1, 2008, CMS will require physicians to submit data on a patient's hemoglobin levels along with any claim for reimbursement of ESAs. However, CMS expects physicians to institute the new regulations immediately.

[Editors' note: As ONI went to press, FDA issued an alert announcing new boxed warnings and other safety-related product labeling changes for ESAs. The changes include a warning that the risks of shortened survival and tumor progression with use of ESAs in cancer patients have not been excluded when ESAs are dosed to reach a hemoglobin of < 12 g/dL and a recommendation that prescribers discuss these risks with their patients. Other new labeling emphasizes that in cancer patients, ESAs have not been shown in controlled trial to improve symptoms of anemia, quality of life, fatigue, or patient well-being.]

Hospital survey on transfusions

Matt Farber, manager of economic and public policy for the Association of Community Cancer Centers (ACCC), warned that taking a patient off an ESA in favor of transfusion may be more costly than continuing the medication.

ACCC surveyed 650 hospitals about this possible economic downside. Of the 125 hospitals responding, 41% said that an increase in blood transfusions of 30% would make it difficult to operate normally. An additional 16.5% said an increase of 10% or less would pose a problem, and 22% claimed any increase would strain resources.

Mr. Farber also said that anecdotal reports suggest that the new policy might indeed be causing a rise in blood transfusions in the hospital setting.

Oncology community responds

Many oncologists perceive the new NCD as yet another example of the government's intrusive presence in their day-to-day delivery of highly complex cancer care. As ASCO and other major cancer organizations exchanged formal letters with policymakers in Washington (see timeline chart on page 20), leading oncologists gathered on October 25 in Chicago to discuss concerns and develop a common response to the new NCD.

In their final statement, which was sent to officials on the Hill, they noted that more than 40 scientific studies support the evidence-based use of ESAs and stated that there is "no evidence of increased mortality or tumor progression when administered in accordance with the FDA label up to 12 g/dL."

In Washington, Dr. Bailes worked with policymakers to find common ground on the disagreement. He sent a letter to Steve E. Phurrough, MD, PhD, secretary of Health and Human Services, stating, "CMS misapplied clinical evidence or did not supply relevant, currently available scientific information when restricting coverage of ESA use in patients with hemoglobin above 10 g/dL." Dr. Bailes also noted that at the May 2007 ODAC meeting convened by FDA, the panel voted to maintain the FDA-approved label that sets the upper ESA limit at 12 g/dL.

In his letter, Dr. Bailes also expressed concern over the new CMS policy requiring ESA treatment to be discontinued if hemoglobin levels reach 10 g/dL or higher. Doctors would also be required to decrease dosing if the hemoglobin level rises more than 1 g/dL within a 2-week period, which would burden patients with weekly blood draws.

"The consequence of this premise would be inconsistent with the FDA-approved labeling, which states that dosing should be titrated to maintain the patient's hemoglobin level," Dr. Bailes said.

Updated ASCO/ASH guideline

On October 22, ASCO and ASH jointly released an updated guideline on the use of ESAs in chemotherapy-related anemia (see Table). According to ASH, the guideline update was developed by examining two meta-analyses that reviewed close to 60 randomized clinical trials.

"Our goal is for these evidence-based recommendations to influence practice standards and result in better care," Samuel Silver, MD, PhD, ASH executive committee councillor, said in an interview with ONI. "Our guidelines are the product of several years of collaborative work, not a reaction to the recent CMS decision."

FDA acknowledges its ESA labeling has caused confusion among oncologists about dosing recommendations. Dr. Silver said part of the confusion stems from FDA's reply to Rep. Peter Stark's request for clarification of the labeling recommendations. In the reply, FDA said it "believes that the approved labeling and the CMS national coverage decision are generally consistent in their recommendations regarding the use of ESAs in patients with cancer undergoing chemotherapy."

Said Dr. Silver, "The term 'generally consistent' is a carefully chosen and rather peculiar bit of legalese, because although the NCD is encompassed within the FDA labeling, there are some patients who, because of the restrictions of dosing above 10 g/dL, are actually excluded by the NCD."

ASH and ASCO propose keeping the hemoglobin concentrations between 10 and 12 g/dL following the first administration of an ESA, but under the new NCD, oncologists would have to wait until a patient's level drops below 10 g/dL and would not be allowed to use the drug until the hemoglobin once again falls below that level, he said.

A dual coverage system?

"It's my understanding that private payers are generally following the ASH/ASCO guidelines, which effectively creates a dual coverage system, one for Medicare beneficiaries and one for the remainder of the private payer community," Dr. Silver said.

Unfortunately, he added, "legislation is not the optimal way of handling this issue. We feel that the national coverage decision should have been an open analytical process, decided by examining the extensive scientific data in the literature that we used to establish the recently issued ASH/ASCO guidelines."

Safety vs profit?

Approximately 450,000 cancer patients receive ESAs each year. The annual cancer-related sales of these drugs is approximately $10 billion, more than any other drug class in oncology. And at $2 billion annually, ESAs are the highest Medicare reimbursement expense.

Thus, money remains a key part of the current controversy. Both Amgen and Johnson & Johnson have come under scrutiny for a variety of promotional activities, as has the industry's practice of rebates, which some say invariably leads to overprescribing. Caught in the rhetorical fallout are many community oncologists who are struggling to keep their practices afloat.

A New York Times article ("Incentives limit any savings in treating cancer," June 12, 2007) asserts that new reimbursement challenges have left oncologists "searching for new income," and using strategies such as providing additional treatments that have the best reimbursements "whether or not the treatments benefit the patients."

So the struggle continues for those in the oncology community who are convinced of the benefit of ESAs and stymied by the CMS's rigid 10 g/dL limit on treatment.