August 2014, Vol 3, No 5

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Bevacizumab Not Cost-Effective in Metastatic Colorectal Cancer


The addition of bevacizumab to chemotherapy for metastatic colorectal cancer is not cost-effective,” according to Daniel A. Goldstein, MD, of Emory University, Atlanta, GA, who led a cost-effectiveness analysis that earned an ASCO Merit Award at the annual meeting.

The lack of cost-effectiveness was demonstrated at a willingness-to-pay threshold of $100,000 per quality-adjusted life year (QALY) in first-line therapy and in second-line therapy when continued beyond progression, he reported at ASCO.

Previous studies from the United Kingdom, Canada, and Japan have indicated a lack of cost-effectiveness for the biologic in the first-line setting, but data from the US perspective have been lacking, as have data for bevacizumab continued beyond disease progression.

While not all studies have been positive, it has become standard practice to use bevacizumab with 5-fluorouracil (5-FU)-based chemotherapy in both the first- and second-line settings, he noted.

Goldstein and colleagues developed 2 Markov models to compare the cost and the effectiveness of 5-FU, leucovorin, and oxa­liplatin (FOLFOX) with or without bevacizumab in first-line treatment, and subsequent chemotherapy with 5-FU, leucovorin, and irinotecan (FOLFIRI) with or without bevacizumab in the second-line setting.

Weibull models were fitted to the published survival curves and were used to extrapolate the cause-specific mortality and progression risks. Costs for administration and management of adverse events were based on Medicare reimbursement rates for hospital and physician services, and drug costs were based on Medicare 2013 average sale prices. The cost of 2 weeks of bevacizumab was figured at $2649.

Cost-Effectiveness Not Shown for Bevacizumab

The use of bevacizumab in the first-line metastatic setting provided an additional 0.29 QALYs (0.41 life years) at an additional cost of $69,354. The incremental cost-effectiveness ratio (ICER) was $240,814 per QALY, Goldstein reported.

Continuing bevacizumab beyond progression (with FOLFIRI) provided an additional 0.11 QALYs (0.16 life years) above FOLFIRI alone, at an additional cost of $39,211. The ICER here was $363,066 per QALY (Table).

In each of the 1-way sensitivity analyses, the ICER of bevacizumab exceeded $100,000 per QALY. The ICER of bevacizumab was greater than $100,000 per QALY in more than 99.9% of probabilistic sensitivity analyses.

“No ICER fell below $100,000 in the first or second line, and we ran this model 10,000 times,” he said. “All fell well above $100,000 and $50,000 QALYs.”

The lowest willingness-to-pay thresholds were $225,000 per QALY in the first-line setting and $370,000 in the second-line setting.

Goldstein added that similar results have been shown when bevacizumab is used in metastatic lung cancer, where the published ICER is $560,000 per QALY.

“The drug could potentially be cost-effective if a biomarker were to be found,” he predicted, “but so far the search for this has been elusive.”

Sandra L. Wong, MD, assistant professor of surgery and a researcher at the Center for Healthcare Outcomes & Policy at the University of Michigan, discussed the study. She commented that a plenary presentation at ASCO, the CALGB 80405 study, found that the addition of bevacizumab (or cetuximab) increased median overall survival to an impressive 25+ months. “There are increasing costs with the addition of this drug, but it’s commensurate with a rise in overall survival,” she commented.

“Dr Goldstein’s study is nicely done and has produced robust data that show, however, that no matter the willingness-to-pay threshold, there is not cost-
effectiveness with bevacizumab,” she said. Wong suggested that the researchers update the study, using the CALGB 80405 results.

“Looking at cost-effectiveness helps inform our conversations with patients, to minimize cost and maximize benefit, leading to value,” she said.

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