ASCO urges CMS to reconsider ESA coverage decision

September 1, 2007

Oncologists have protested to the Centers for Medicare & Medicaid Services (CMS) that new rules restricting coverage of erythopoiesis-stimulating agents (ESAs) contradict Food and Drug Administration's approved labeling for the drugs and tie the hands of physicians treating cancer patients with chemotherapy-induced anemia.

WASHINGTON—Oncologists have protested to the Centers for Medicare & Medicaid Services (CMS) that new rules restricting coverage of erythopoiesis-stimulating agents (ESAs) contradict Food and Drug Administration's approved labeling for the drugs and tie the hands of physicians treating cancer patients with chemotherapy-induced anemia. The regulations control payments for use of darbepoetin alfa (Aranesp, Amgen) and erythropoietin alfa (Epogen, Amgen; Procrit, Ortho Biotech).

The new Medicare coverage determination has also attracted congressional attention. A majority of members of both Houses have written CMS to express their concerns, and Sens. Arlen Spector
(R-Penn), Tom Harkin (D-Iowa), and Frank Lautenberg (D-NJ) have introduced a resolution in the Senate ordering CMS to confer with the oncology community and make appropriate revisions to its policy.

Starting January 1, 2008, physicians will be required to submit data on a patient's hemoglobin levels along with any claim for an ESA. However, CMS expects physicians to begin following the coverage decision immediately.

CMS put out the new rules based on a policy that patients with anemia secondary to chemotherapy should receive ESAs only when their hemoglobin level is less than 10 g/dL.

"The new policy also denies coverage of ESAs whenever a patient's hemoglobin goes above 10 g/dL. This latter restriction is inconsistent with both the FDA-
approved labeling and national guidelines, and we strongly disagree with this restriction," Joseph S. Bailes, MD, chair of ASCO's Government Relations Council, said in a letter to Steve Phurrough, MD, MPA, director of CMS's Coverage & Analysis Group, Office of Clinical Standards & Quality.

In his letter, Dr. Bailes pointed out that the FDA-approved label for Procrit/Epogen indicates that the dose "should be titrated for each patient to achieve and maintain the lowest hemoglobin level sufficient to avoid the need for blood transfusion and not to exceed 12 g/dL." The labeling for darbepoetin is similar.

The CMS approach, Dr. Bailes said, "is entirely different from the instructions for use specified in the FDA-approved label." Further, he noted, ASCO/ASH guidelines recommend consideration of ESA therapy when hemoglobin falls below 10 g/dL (for most patients) with a treated hemoglobin not to exceed 12 g/dL.

One-time dose escalation

ASCO's second concern: CMS's new payment policy only allows a one-time dose escalation of 25% for hypo- or non-responders—patients with a rise in hemoglobin of less than 1 g/dL over 4 weeks of treatment. Dr. Bailes pointed out that the FDA-approved label for hypo- or non-responders allows for increases in weight-based dosing by 100%.

"Moreover," Dr. Bailes wrote, "the allowance for the 25% dose escalation applies only to the 5th week of ESA therapy within any one course of chemotherapy. The effects of myelosuppressive chemotherapy can be cumulative within any one course of chemotherapy, and this new restriction does not allow for dose escalation further into a course of chemotherapy."

The CMS decision also creates problems for responders. If patients respond to standard starting doses in the first 4 weeks, but their hemoglobin remains below 10 g/dL, they then enter the "maintenance" phase (from the 5th week through the end of that chemotherapy course, plus 8 weeks), Dr. Bailes wrote.

He protested that "after the 5th week, if a patient fails to respond as well to the standard dose, for example, due to the cumulative toxic effects of myelosuppressive chemotherapy, the clinician does not have the option of even the arbitrarily set 25% dose increase, and is allowed only to continue with the standard dose. This restriction interferes with the clinician's ability to titrate the dose as clinical judgment and the best interests of the patient dictate."

ASCO also expressed concern over provisions in the new CMS policy that require ESA treatment to be discontinued (if hemoglobin is 10 g/dL or higher) or the dose decreased (if hemoglobin is less than 10 g/dL) if hemoglobin rises by more than 1 g/dL within 2 weeks.

"We strongly disagree with CMS on the basic premise of disallowing ESAs above a hemoglobin of 10 g/dL," Dr. Bailes wrote. ASCO pointed out that patients will need weekly blood draws in order to determine the rate of hemoglobin rise over any 2-week period.

Dr. Bailes also wrote Louis B. Jacques, MD, director of CMS's Division of Items and Devices in the Coverage & Analysis Group. He pointed out that "under the new CMS policy, a patient's hemoglobin could repeatedly fall below 10 g/dL following termination of coverage at the end of
4-week periods. This consequence would be inconsistent with the FDA-approved labeling," which states that dosing should be titrated to maintain the individual's hemoglobin level.

Transfusion need will rise

The Association of Community Cancer Centers (ACCC) also protested that the new CMS policy could result in a demand for many more blood transfusions. A survey of the ACCC hospital membership showed that 40.9% of respondents indicated that a 30% increase in demand would cause problems in carrying out normal transfusion services. Another 16.5% said even a 10% or less increase in demand for blood transfusions would cause problems, and 21.7% said any increase would result in problems.

The survey was sent to 650 ACCC member hospitals, and 115 responded—including rural (20%), urban (39%), and suburban (41%) hospitals.

One issue that did not get the attention of CMS, Christian Downs, JD, MHA, ACCC executive director, emphasized, "was the impact on hospitals, which are going to bear the brunt of increased blood transfusions."

Senate resolution

The resolution introduced into the Senate echoes this concern. "Such restriction could increase blood transfusions and severely compromise the high quality of cancer care delivered by physicians in the United States," it states. The resolution points out that CMS had said that impact on the nation's blood supply was not relevant for consideration in this national coverage determination.

The proposed Senate resolution asks CMS to immediately reconsider its findings in the National Coverage Determination on the Use of Erythropoiesis Stimulating Agents in Cancer and Related Neoplastic Conditions (CAG-000383N). The senators want CMS to consult with the clinical oncology community and "implement appropriate revisions to such final National Coverage Determination as soon as feasible."