ESAs spared ax at ODAC meeting

Erythropoietin-stimulating agents were spared the ax when FDA’s Oncologic Drugs Advisory Committee (ODAC) decided by a vote of 13-to-1 that ESAs should remain available for use in cancer patients with chemotherapy-induced anemia. ODAC did, however, recommend further restrictions on ESA use in these patients (see Table on page 8), some of which created concern and confusion among oncology leaders at the meeting.

 Since the 2007 ODAC meeting, new data from two studies became available, prompting FDA to call yet another ODAC meeting on this issue. The PREPARE study, a European neoadjuvant breast cancer trial, showed a slight numeric decrease in survivorship in the ESA arm, compared with the placebo arm. GOG-191, a gynecological group study of cervical cancer patients, also showed an increase in numeric mortality in the ESA arm. However, as with previous data showing problems with ESAs, both studies targeted hemoglobin levels higher than the currently approved product label.

“To be perfectly honest, there really weren’t any new data at the ODAC meeting. The arms of both studies were not statistically significantly different; there was just a trend,” said Samuel Silver, MD, PhD, of the University of Michigan and chair of ASH’s subcommittee on reimbursement.

Dr. Silver told Oncology News International that he felt there was no new information presented at the meeting that warranted changing the indications or labeling of ESAs. He was also concerned about confusion coming out of some of the rulings.

Who defines ‘potentially curative’?

“The committee voted overwhelmingly to modify ESA indications for potentially curative treatment. So that begs the questions about exactly what is curative treatment?” he said. Who determines whether you’re treating for cure? How will the language be written to make that clear? he asked.

“In lymphoma patients you could have stage IV, widely disseminated, intermediate-grade lymphoma treated curatively or as you could have a low-grade lymphoma with a lesser stage that cannot be treated curatively,” he said.

ASCO executive vice president and ONI board member Joseph S. Bailes, MD, said that ASH and ASCO are collaborating on an education initiative about ESA usage.

 “This is an important initiative simply because of how much confusion can be generated in the community setting by ODAC’s action,” Dr. Bailes told ONI.

 He stressed that it is important for community practitioners to keep abreast of the changes in ESA reporting.

 “For example, you must report the most recent hemoglobin or hematocrit levels on any claim for a Medicare patient receiving ESA administrations or Part B anti-anemia drugs other than ESAs that are not self-administered,” Dr. Bailes commented.

Worries over MDS patients

According to Dr. Silver, the ASH membership was apprehensive about the ODAC meeting, fearing it might result in decisions that could hinder the availability of ESAs for patients with low-grade myelodysplastic syndromes.

“This is not a labeled indication. However, we were concerned that if the committee voted to discontinue marketing to treat anemia resulting from chemotherapy, its availability to patients with MDS might be compromised. We were glad that didn’t happen,” he said.

Dr. Silver testified to FDA that recent studies show there could be an increase in survival in patients with low-risk MDS who receive ESAs.

“Our hope is that these agents continue to be available, but currently for Medicare patients with MDS, it’s not a national coverage decision, it’s based upon the decision of the local carrier’s medical director,” he said.

Reiterating Dr. Bailes concern about the need for educational materials on ESA use in cancer patients, Dr. Silver said, “We need good communication tools for physicians to use and patients to read. These materials need to cover the risks and benefits of the ESAs; the risk and benefits of transfusions, because transfusions are not a risk-free modality either; and the risks and benefits of not treating anemia. ASH and ASCO will be getting together to write these communication tools soon.”

A compelling story

Another ODAC attendee, David Henry, MD, of Pennsylvania Oncology Hematology Associates, told ONI that he is concerned about cancer patients, who oftentimes are a silent presence during these emotional political and financial decisions.

He said that the FDA/ODAC public comment period that he participated in lasted about 1 hour, including comments from about 20 speakers picked at random.

“Most of us were physicians, but two were patients,” he said.

He said a woman [Karen Pasquelleto] went to the mike without notes and simply said that some 21 months ago she delivered a child and 1 month later was told she had metastatic incurable colorectal cancer and 6 months to live. She said that thanks to modern oncology care, she is alive and doing well some 20 months later.

She attributed this to the wonderful care of her oncologist, and to the ESAs she had been receiving. She stressed that her transfusion requirement had been eliminated, and she was able to spend more time at home with her husband and family.

“She told this compelling story under her allotted 3 minutes, without notes and with eloquence and passion,” Dr. Henry commented. “At the conclusion of her remarks, she got applause from the crowd of some 400 people.” 

ODAC recommendations to FDA on ESA use
• Preserve the chemotherapy-induced anemia indication for ESAs.
• Do not restrict ESA use only to patients with small-cell lung cancer.
• Modify the current indication to include a statement that ESA use is not indicated for patients receiving potentially curative treatments.
• Modify the current indication to include a statement that ESA use is not indicated for patients with metastatic breast cancer and/or head and neck cancer.
• Require the use of a signed informed consent/patient agreement for the treatment of chemotherapy-induced anemia, but do not mandate a restricted distribution system for oncology patients receiving ESAs.