ESAs Not Cost-Effective in Cancer, and Use Is Declining
By Zosia Chustecka
Medscape Medical News
May 18, 2010 — Another economic evaluation has found that the use of erythropoiesis-stimulating agents (ESAs) for anemia in cancer patients is not cost-effective, even when the model considers only the more conservative uses of these agents, following the current guideline recommendation that they only be used for chemotherapy-induced anemia and within specified hemoglobin targets.
"There is no evidence to suggest that ESA is more economically attractive in this subgroup than in any other," say the authors.
Using ESA to treat anemia related to cancer does not represent good value for money.
"Available evidence suggests that using ESA to treat anemia related to cancer does not represent good value for money," they conclude in a paper published online April?19 in Cancer.
The pendulum is swinging away from the use of these agents, with "less enthusiasm for widespread use," said lead author Scott Klarenbach, MD, assistant professor at the University of Alberta in Edmonton.
"There is increasing awareness of the harms of ESAs," he said, not only in populations with cancer (where an increase in mortality has been reported), but also in populations with chronic kidney disease and end-stage renal disease. It is also not clear whether the purported increases in quality of life associated with these agents are "strikingly positive," he added.
"These issues, in addition to the substantial drug-acquisition costs, have led to more questioning about the value of these agents," he told Medscape Oncology.
There has been a marked decline in the use of ESAs in cancer since late?2006/early?2007, when the first alerts about harm appeared, according to a news brief in the May?5 issue of the Journal of the National Cancer Institute (2010;102;592-593).
A further decline in use is now expected, after the recent implementation of a risk evaluation and mitigation strategy by the US Food and Drug Administration for the use of ESAs in cancer patients. This mandates training for oncologists that needs to be repeated every 3 years and provides detailed information and informed-consent forms for patients. It is expected that both of these measures will decrease the use of these agents and increase reliance on blood transfusions to treat anemia instead, the news brief notes.
"I'm not familiar with the details of this program, but I would strongly agree with very careful use of these medications in the cancer population," Dr. Klarenbach said.
There are also lessons to be learned here, he suggested. Large-scale clinical trials to evaluate benefit and harm should be conducted "prior to widespread use of medications such as ESAs," he emphasized.
"It is also important to conduct cost-effectiveness evaluations prior to widespread use, in order to ensure that finite healthcare resources are used in the most appropriate manner to improve outcomes for our patients," he said.
Cost-Effectiveness Analysis
For their economic evaluation, Dr. Klarenbach and colleagues created a decision model based on the Canadian public healthcare system, and input data from a recent systematic review (CMAJ. 2009;180:E62-E71).
The authors report that, compared with supportive transfusions only, conventional ESA treatment was associated with an incremental cost per quality-adjusted life-year (QALY) gained of $267,000 during a 15-week time frame. When they adjusted these analyses and included multiple assumptions about quality of life, all favoring ESA, the lowest incremental cost per QALY gained was $126,000.
They then performed additional scenario analyses to simulate the use of ESA in accordance with the latest guidelines from the American Society of Clinical Oncology (ASCO) and the American Society of Hematology (ASH), which recommend that ESAs be used only for the treatment of chemotherapy-induced anemia in cancer patients (and not anemia associated with the cancer itself); they also specify initial and target hemoglobin levels.
This is the first such analysis to consider this more conservative use of ESAs, the authors note.
When they considered ESA use according to the ASCO/ASH guidelines, the results were "quantitatively lower," but in all the analyses, the incremental cost per QALY gained exceeded $70,000, and in many cases exceeded $100,000.
"Overall, these findings suggest that even with the more conservative administration and dosing, ESA therapy for patients with cancer is unlikely to be economically attractive when using a commonly accepted threshold of economic attractiveness," they conclude.
Comparator Was Blood Transfusions
The comparator in this study was blood transfusions as required; thus, the cost-effectiveness ratio is relative to this standard of care, said Dr. Klarenbach. Costs to the patients, such as the time taken and the cost incurred in traveling to a health center for a blood transfusion, were not included in this analysis, he explained, but this has been looked at in other studies.
"The willingness to pay that has been reported in other studies is less than $1000. Given the very high cost per QALY we found, formal incorporation of this relatively limited patient willingness to pay would have no meaningful impact on overall conclusions," he added.
The authors note that their economic analysis considered patients who were candidates for blood transfusions. They also point out that there are specific subpopulations in whom blood transfusions are difficult (e.g., patients with iron overload) or unacceptable (e.g., Jehovah's Witnesses), and that access to health centers that perform transfusions could pose problems.
The researchers have disclosed no relevant financial relationships.
