Inappropriate Use of Antineoplastic Agents Costing Insurers Millions of Dollars, Driving Up Health Care Costs

Prescribing medications in situations in which there is no evidence of efficacy is a major contributor to the escalating cost of health care in the United States. A recent retrospective study has shown, for example, that non–evidence-based use of just three antineoplastic agents, bevacizumab, capecitabine, and panitumumab, in patients with metastatic colorectal cancer cost one private insurer $2,009,480 between early 2007 and mid-2010. This amount did not include associated expenses of medication such as infusion, diagnostics, hospitalizations, and managing adverse effects.

A research team from The University of Chicago, Case Western Reserve University, and the United Health Group of Edina, Minn., harvested reimbursement data from United Healthcare on its insured patients with metastatic colorectal cancer (Abstract 6002). Jonas A. de Souza, MD, of The University of Chicago, presented results during the Clinical Science Symposium “Emerging Issues in Comparative Effectiveness Research,” held on Tuesday, June 7.

One thousand forty-one individuals were identified who met all the inclusion criteria, including having been treated with at least one medication approved expressly for use in metastatic disease — “metastatic-only” agents. Investigators then compared the treatment histories of those patients with National Comprehensive Cancer Network (NCCN) guidelines to identify inappropriate therapies. Patients with second primary lesions, with Medicare supplemental insurance, or with fewer than 30 days of claims related to metastatic colorectal cancer were excluded from the analysis.

Among 884 patients who had been treated with bevacizumab, 90 (10%) had received it beyond disease progression, resulting in 636 claims for reimbursement. This use is contrary to the NCCN guideline that advises, in part: “There are insufficient data to support continuation of bevacizumab with a second-line regimen after progression on a bevacizumab- containing first-line regimen, and such continuation of bevacizumab beyond progression is not recommended.”

Based on the average sale price of bevacizumab in January 2011, as well as on the assumption that the average recipient weighed 70 kg and stood 170 cm, the approximate cost of this inappropriate use was $1,326,696. NCCN guidelines also indicate that “[t]he use of single-agent capecitabine as salvage therapy after failure on a fluoropyrimidine-containing regimen has been shown to be ineffective and is, therefore, not recommended.” Nevertheless, 49 of 121 patients (40%) who received capecitabine as single-agent second-line therapy had previously been so treated. UnitedHealthcare received and paid 218 reimbursement claims for a total cost of approximately $621,463.

Cetuximab and panitumumab are both approved for use in metastatic colorectal cancer. The NCCN guidelines recommend explicitly against their tandem use. “There are no data, nor is there a compelling rationale, to support the use of panitumumab after clinical failure on cetuximab or the use of cetuximab after clinical failure on panitumumab. As such, the use of one of these agents after therapeutic failure on the other is not recommended.” Despite this recommendation, six of 38 (16%) patients identified as having been treated with panitumumab were given the drug after a failed course of cetuximab, at an approximate cost to UnitedHealthcare of $69,665.

Following the presentation, Discussant Marcelo Blaya, MD, of Tulane University Health Sciences Center, discussed the data in the context of overall survival in colorectal cancer in the past decade as a result of new drug classes. He pointed out that although the approximate monetary cost of non– evidence-based treatments is calculable, the social costs are not. These potent agents may be difficult to tolerate, and the introduction of adverse events with little prospect of benefit tilts the therapeutic index entirely to the negative side.