Zosia Chustecka

June 04, 2015

CHICAGO — What a difference a year makes.

Last year, a large, federally funded study in colorectal cancer found that two targeted antibodies combined with chemotherapy showed the same excellent efficacy, improving overall survival by 6 months compared with results seen in previous trials. The conclusion was that clinicians can choose use either; it was "dealer's choice."

But this year, a cost analysis conducted using the same data shows that one of these combinations costs nearly $40,000 more than the other. And the conclusion is quite different.

"The outcome is identical, the quality of life is identical, but the cost of [one]...is less than half of the other," pointed out Leonard Saltz, MD, from Memorial Sloan Kettering Cancer Center, New York City.

"That doesn't leave us with two identical regimens and with 'dealer's choice,' " he said.

"That leaves us with one regimen that is the clear, better choice," he said.

Dr Saltz highlighted this study here at the American Society of Clinical Oncology (ASCO) 2015 Annual Meeting during his plenary presentation on value.

The data come from the Alliance/SWOG 80405 study, conducted in 1137 patients with metastatic colorectal cancer (KRAS wild-type), who were treated with a chemotherapy backbone and either bevacizumab (Avastin, Genentech, Inc) or cetuximab (Erbitux, ImClone Systems Incorporated) as first-line therapy.

The chemotherapy used was FOLFOX (oxaliplatin, 5-fluorouracil, and leucovorin) or FOLFIRI (irinotecan, 5-fluorouracil, and leucovorin); the decision of which one to use was left to the treating physician and the patient (most [73.4%] used FOLFOX).

The trial randomly assigned patients to receive either bevacizumab (5 mg/kg once every 2 weeks) or cetuximab (a loading dose of 400 mg/m² followed by 250 mg/m² once a week).

The primary efficacy results from this study, which were presented at last year's ASCO meeting, showed no difference in efficacy between the two antibodies. In both arms, the overall survival was nearly 30 months, which was described as "remarkable" because it raised the bar from the 24 months or so reported in previously studies.

Cost Analysis

At this year's ASCO meeting, a cost analysis of this study was presented by Deborah Schrag, MD, MPH, from the Dana-Farber Cancer Institute, in Boston, Massachusetts. She noted that this was not a cost-effectiveness study, because the two regimens were equally effective and have similar quality-of-life results; this analysis turned into a "cost minimization" study.

There is a large difference in the cost of the antibodies. Determined on the basis of 2014 Medicare data, the drug cost of one cycle (8 weeks) for an average person is $9324 for bevaczimab and $20,856 for cetuximab.

"Perhaps we could have just stopped there. This could have all been done on the back of an envelope," she commented, to much audience laughter.

But total costs are not always driven solely by the drug costs; they can also be driven by the drug's toxicity profile and, in particular, by whether hospitalization is needed to deal with the drug's side effects. "And as we all know, that is where the big-ticket healthcare costs kick in," she said.

Dr Shrag explained that the two antibodies have different toxicity profiles, and both have rare but potentially severe and sometimes even fatal side effects. With bevacizumab, it is arterial/venous clots (seen in about 1% to 5% of patients), which can lead to myocardial infarction and stroke; with cetuximab, it is interstitial lung disease (seen in fewer than 0.5% of patients) and fatal infusion reactions (seen in fewer than 1%) as well as cardiac arrhythmias.

So the analysis also tried to capture the cost of treating the toxicity by adding in the cost of stays in hospital or intensive care units, although she noted that these costs were estimated.

Table. Cost of First-Line Treatment of Colorectal Cancer (Alliance/SWOG 80405)

  Bevacizumab Cetuximab
Chemotherapy $2894.00 $2616.00
Antibody $33,500 $71,718
Hospital/acute care $28,951 $28,494
Total costs $66,075.00 $105,339.00


The analysis found that the hospital/acute care costs were similar for the two regimens, as were the costs for the chemotherapy. What stood out, and what drove the difference between the two regimens, was the difference in the cost of the antibodies.

Cetuximab costs twice as much as bevacizumab, a finding similar to the results of that "back of the envelope" analysis, she noted. This difference in drug cost accounted for most of the difference ― almost $40,000 ― between the total costs for each treatment arm.

"Chemotherapy with bevacizumab cost less and achieves similar, even identical, survival and quality-adjusted survival," Dr Schrag concluded. Because patients incur significant costs from co- pays, she said there is a good case to be made for this being the first-line treatment, "and it is certainly what I use in my practice."

She also commented that if the price of cetuximab were to be reduced by about 40%, the choice between the antibodies would then become cost-neutral, and this is something to bear in mind during the coming months, as cetuximab comes off patent.

In his discussion of this presentation, Peter Bach, MD, from Memorial Sloan Kettering Cancer Center, homed in on this point and suggested that clinicians should refuse high prices (as, indeed, his institution had done for another colorectal cancer drug). He noted that Dr Schrag had mentioned that she does not use cetuximab in her own clinic, but he wondered, "Why not say no more generally? Why treat prices as immutable?"

He also emphasized the importance of these new discussions about costs and value. "We are in the midst of payment reform, and CMS has decided that it will move towards value-based payments, which will necessarily incoprate costs," he said. "We have to understand which part of the needle we can move, and in order to do this, we have to understand the landscape of costs and how they are linked to particular diseases."

Dr Schrag has reported no relevant financial relationships.

American Society of Clinical Oncology (ASCO) 2015 Annual Meeting. Abstract 6504. Presented May 30, 2015.


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.