FROM JOURNAL OF CLINICAL ONCOLOGY

Adding bevacizumab to standard chemotherapy for metastatic colorectal cancer yields a minimal incremental benefit at high incremental cost per quality-adjusted life year, according to a report published online Feb. 16 in the Journal of Clinical Oncology.

In a cost-effectiveness analysis using computer modeling based on the results of the most recent randomized phase III clinical trials of the agent, even the best-case scenario produced an incremental cost-effectiveness ratio of more than $200,000 per QALY. Probabilistic sensitivity analyses also showed that the likelihood of bevacizumab being cost effective was 0% as either first- or second-line treatment for a willingness-to-pay threshold of $100,000 per QALY, said Dr. Daniel A. Goldstein of Emory University, Atlanta, and his associates.

At present, it is standard practice to add bevacizumab to chemotherapy for metastatic colorectal cancer in both first- and second-line settings, but the modest survival benefit conferred by the agent in this patient population, together with its very high cost, have raised concerns about its cost effectiveness.

Dr. Goldstein and his associates developed computer models of the clinical effectiveness and direct medical costs associated with bevacizumab using data from the most recent randomized controlled trials. They then performed both internal and external validation studies, which demonstrated that the survival curves generated by their models closely approximated those that actually occurred in other clinical trials of the agent.

As first-line therapy, FOLFOX alone provided 1.31 QALYs at a cost of $32,561, while FOLFOX plus bevacizumab provided 1.41 QALYs at a cost of $92,112. The incremental cost-effectiveness ratio for FOLFOX plus bevacizumab was $571,240 per QALY. As second-line therapy, FOLFIRI alone provided 0.64 QALYs at a cost of $7,443, while FOLFIRI plus bevacizumab provided 0.75 QALYs at a cost of $46,764. The incremental cost-effectiveness ratio for FOLFIRI plus bevacizumab was $364,083 per QALY. A threshold between $50,000 and $100,000 is usually used to define a cost-effective health intervention, the investigators said (J. Clin. Oncol. 2015 Feb. 16 [doi:10.1200/JCO.2014.58.4904]).

In sensitivity analyses that tested a broad range of variations in each parameter – such as different drug costs, physician fees, and treatment toxicities – the incremental cost-effectiveness ratio remained higher than $200,000 per QALY in every case, even in the “best case scenario” model.

These findings closely accord with those of similar studies in other countries, even though there were significant differences in modeling approaches, costs, and health care systems. In the United Kingdom, adding bevacizumab to FOLFIRI cost the equivalent of $102,000 U.S. per QALY. In Canada it cost the equivalent of $120,000 U.S. per QALY, and in Japan it cost the equivalent of $113,000 U.S. per QALY, Dr. Goldstein and his associates said.

Presumably, the poor cost/benefit ratio could be improved if an effective biomarker were developed and used to select only the patients most likely to benefit for bevacizumab therapy, they added.

No funding sources were reported for this study. Dr. Goldstein reported having no financial disclosures; his associates reported numerous ties to industry sources, mostly through research funding of their institutions.

tor@frontlinemedcom.com

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