Ixabepilone in Metastatic Breast Cancer: Small Benefit at High Cost

Nick Mulcahy

May 07, 2009

May 7, 2009 — Ixabepilone (Ixempra) for metastatic breast cancer is an example of a cancer drug that adds "a small benefit at a high cost," says an editorial in the May 1 edition of the Journal of Clinical Oncology.

The editorial accompanies a new cost-efficacy study in the same issue of the journal that found that the addition of ixabepilone to capecitabine (Xeloda) adds about $31,000 to the overall medical costs of metastatic breast cancer while providing about 1 more month of "quality-adjusted" survival.

Most of the $31,000 in higher costs is attributable to the cost of ixabepilone.

"Most of the $31,000 in higher costs is attributable to the cost of ixabepilone," said lead author Shelby Reed, PhD, from Duke's Center for Clinical and Genetics Economics in Durham, North Carolina, in an interview with Medscape Oncology. She also said that she agreed with the comments in the accompanying editorial.

Medscape Oncology asked Bristol-Myers Squibb, the makers of ixabepilone, to comment on the editorialists' "small benefit–high cost" assessment of ixabepilone. "There are inherent challenges in assessing cost effectiveness in areas of high unmet medical need, such as relapsed metastatic breast cancer," said Sarah Koenig, a company spokesperson.

Approved in US, But Not in Europe

Ixabepilone was approved in the United States in 2007 and is indicated for the treatment of metastatic or locally advanced breast cancer in patients after failure of an anthracycline and a taxane.

However, the European Medicines Agency's review committee recently recommended that ixabepilone be rejected for approval because of concerns that the drugs' benefits do not outweigh the risks, including neuropathy.

Ixabepilone provides another advance in treatment for patients with metastatic breast cancer.

Nonetheless, editorialists Bruce E. Hilner, MD, and Thomas J. Smith, MD, from Virginia Commonwealth University and the Massey Cancer Center in Richmond, Virginia, write that ixabepilone provides "another advance in treatment for patients with metastatic breast cancer"

However, their comments about the drug's pricing were less positive.

The pricing of ixabepilone and some other recent cancer drugs "can be justified only by a logic of pricing" that is "independent of the absolute or duration of benefit," assert the editorialists. They then write: "Profiteering, the act of makinga profit by methods considered unethical, such as raising pricesafter a natural disaster, is a pejorative term that we believecan be applied to this recent trend where a life-threateningdisease is the natural disaster."

Ixabepilone plus infusion currently cost approximately $4570 per cycle, said Dr. Reed. The drug would only be cost effective if this cost was cut in half, she and her study coauthors calculated.

As it is, the price of ixabepilone is higher than that of other patented treatments for advanced breast cancer, write the study authors.

Complex Calculations, Important Exercise

In the new cost-efficacy study from Dr. Reed and her Duke colleagues, the survival estimates were generated from an earlier phase 3 randomized clinical trial of ixabepilone that had progression-free survival as the primary end point.

In that phase 3 clinical trial, the patients had metastatic breast cancer and were progressing after anthracycline and taxane treatment. The addition of ixabepilone to capcitebine increased progression-free survival by a median of 1.6 months.

In their cost-efficacy study, Dr. Reed and her fellow investigators attempt to use a modeled survival estimate to evaluate the cost-effectiveness of adding ixabepilone to capcitebine in this setting.

The importance of this exercise was explained by the investigators. "As more treatment options become available, information aboutexpected costs and health gains associated with treatments beforethey become standard care may help to moderate the growth ofhealth care expenditures," they write.

First, the investigators multipliedthe per-cycle cost of ixabepilone plus capecitabine (approximately$6100), and capecitabine alone ($1900), by the average numberof treatment cycles (6.4 and 5.9, respectively) and subtractedthe difference to arrive at an incremental cost of approximately$28,000.

They then took the 1.6 month difference in progression-free survival with ixabepilone and converted it into life-years saved with the addition of ixabepilone(0.13), and then multiplied life-years saved by the mean quality-of-life score, which was lower for ixabepilone (0.67) than for capecitabine (0.77). In the end, the investigators arrived at a value for the gain in quality-adjusted life-years (QALYs) with ixabepilone (0.09). "Dividing the increase in costs by the gainin QALYs yields a cost-effectiveness ratio of approximately$321,000 per QALY," they write.

Quality-Adjusted Survival

The Duke researchers actually estimated a gain in life expectancy of about 2 months in women with metastatic breast cancer treated with ixabepilone plus capecitabine, compared with capecitabine alone. The total medical cost of the 2 months for the patients treated with ixabepilone plus capecitabine was estimated to be more than $60,000.

However, when quality-of-life scores were factored into the cost-efficacy analysis, the researchers' concluded there was about 1 "quality-adjusted" month's difference in survival between ixabepilone plus capecitabine and capecitabine alone.

Patients receiving ixabepilone were more likely to experience moderate to severe toxicities, especially sensory peripheral neuropathy and hematologic toxicity, the authors noted.

Cost-Effectiveness Evaluations: Not Used, But Needed

The editorialists examined what cost-effectiveness threshold should be a cut-off point for determining whether drugs are worthwhile or not. In doing so, they noted that Medicare and commercial and state Medicaid plans do not use cost-effectiveness data — even though "almost all use costs in some form when evaluating new interventions."

Both the study investigators and the editorialists, using different methods, agree that the efficacy of ixabepilone necessitates that its price be cut in half before it can be considered to have an acceptable cost-effectiveness threshold. "The easiest way to improve cost-effectiveness is to cut the price," summarized the editorialists.

They also believe that establishing some kind of cost-effectiveness threshold, which they pegged at somewhere between $140,000 and $200,000 per QALY, is imperative. At least 100 new molecules for cancer are currently in phase 3 clinical trials, they note. "We will have to make some hard choices about alternative use of public funds if we accept paying $31,000 for 1 month of QALY," they write.

J Clin Oncol. 2009;27:2185-2191, 2111-2113.

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