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Bevacizumab Wins Cost-Effectiveness Analysis in First-Line Metastatic Colorectal Cancer

An economic analysis of the landmark CALGB/SWOG 80405 study, which compared bevaciz­umab versus cetuximab in patients with metastatic colorectal cancer, declares bevacizumab the clear winner, as its total cost is $39,000 less than cetuximab.

“Chemotherapy plus bevacizumab costs less and achieves very similar survival and quality-adjusted survival as chemotherapy plus cetuximab for first-line treatment of KRAS wild-type metastatic colorectal cancer,” according to Deborah Schrag, MD, MPH, Dana-Farber Cancer Institute, Boston, MA.

The phase 3 head-to-head comparison was presented at the plenary session last year by Venook and colleagues. At a median follow-up of 24 months, no significant differences were observed between the treatment groups; median overall survival and progression-free survival were 29 months and 10.8 months, respectively, with bevacizu­mab/chemotherapy, and 29.9 months and 10.4 months, respectively, with cetuximab/chemotherapy.

“Our study objective was to determine the most cost-effective treatment strategy for first-line metastatic colorectal cancer,” said Schrag. “The cost-effectiveness analysis was prospectively planned for CALGB/SWOG 80405, given the high costs of all the study arms.”

She cited the 2014 cost for 1 cycle (8 weeks) of these treatments in the average patient as $9324 for bevacizumab and $20,856 for cetuximab. This was based on an average selling price of $66.6/10 mg for bevacizumab given at 5 mg/kg every 2 weeks, for a total of 1400 mg in an 8-week cycle, and $53.3/10 mg for cetuximab given at 250 mg/m2 every 2 weeks (400 mg/m2 for the first dose), for a total of 3913 mg in an 8-week cycle.

She and her coauthors figured the incremental cost-effectiveness and cost- utility ratios for the 2 treatment strategies. Their analysis took into account the utilization and cost of chemotherapy (leucovorin, fluorouracil, oxaliplatin [FOLFOX] or leucovorin, fluorouracil, irinotecan [FOLFIRI]) and the major care episodes related to treatment. They assumed vial sharing and the efficient use of every milligram of drug, that end-of-life costs were similar between the arms, that postprogression treatment intensity was identical between the arms, that all hospital regular bed days and intensive care unit days were “created equal,” that genomic testing costs were identical, and that the arms were similar in terms of provider visits and chair intensity.

The efficacy of the regimens was similar, as was quality-adjusted life-years (QALYs), Schrag noted, while pointing out that the 2 drugs differ in toxicities but are generally well tolerated.

Life-years and QALYs, based on the EQ-5D measurements of health outcomes, were 2.88 and 2.75, respectively, for bevacizumab, and 3.03 and 2.90, respectively, for cetuximab. The only difference in a subjective measurement was greater “skin satisfaction” with bevaciz­umab, as expected.

“There were no meaningful differen­ces” in subjective outcome measures between the arms, Schrag indicated.

Large Cost Difference Observed

The analysis did, however, reveal large cost differences between the treatment arms, which stemmed from differences in the cost of the biologics (Table).

Schrag indicated that if the average selling price of cetuximab were reduced by 45%, the cost would be neutral.

Peter Bach, MD, MAPP, Director of the Center for Health Policy and Outcomes at Memorial Sloan Kettering Cancer Center, New York City, commented on Schrag’s study.

“We are in an era where we have decided on a hierarchy of comparative decision making in cancer that begins with efficacy, then is followed by toxicity, and then cost,” he said.

“Dr Schrag’s analysis could have been ‘back-of-the-envelope,’ but she spent lots of effort to lay this out. And she found no statistically significant difference, whether in life-years or QALYs, with 2 drugs that cost considerably different against dealer’s choice backbone chemotherapy,” he said.

“Benefits to some extent are constrained by biology, as are harms. But prices and costs? We accept these prices, put them into our cost-effectiveness analysis...Why not close this loop? If drugs are equal except for cost, why not just say no to the higher-cost agent?”

In fact, that is just what Schrag does. “There’s a good argument” for bevaciz­umab first-line, “and that is what I use,” she said.

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