Finally, could you briefly discuss some of the cost issues associated with adding biologics to CT? How does the cost of bevacizumab compare with that of cetuximab? Given the outcome of the CALGB/SWOG 80405 study, what do you think is a cost-effective approach to using these agents?
Cost today is a big issue, as it should be. A lot of these biologics are extremely expensive and they add significant cost to chemotherapy and to the care of patients. This is not particular to bevacizumab and siltuximab, but to most biologics. The problem is two-pronged, with the problems of cost and the problem of access. The United States may not be so much, but worldwide it could be a problem.
In the United States, in terms of when you think about adding a biologic to chemotherapy, you have to be able to justify whether or not there is enough benefit to justify the cost. The issue of cost with all these biologics is central to how we think about utilizing them in the treatment of colorectal cancer. Resources are limited and cost is becoming an issue when we look at total healthcare. The question is always "is there a good way for us to measure how much benefit is worth it?"
There are different models that have been looking at the cost analysis, from a very simple to the more complicated cost models. Unfortunately all these models have their complexities and their issues, and they're all mostly retrospective rather than prospective, which makes them very difficult to interpret and understand. What's clear is we know they're costly, but we also know they do benefit patients and typically most of the cost are measured around the median. Most patients are not at that median. Some don't benefit at all and others benefit tremendously, and then if you look at the end tail of the curve, some patients live 7 or 10 years and even longer.
The question is "can you look at the cost just based on that median improvement, and how can you improve the cost:benefit ratio?" One way to do it, and it really doesn't exist today, when you look at bevacizumab, we don't have a biomarker. We don't know who the patients are that benefit the most on this side of the curve and who don't. So it's very difficult to make sense out of this and it's difficult to make sense out of cost. The EGFR inhibitors, we know that half of the patients don't benefit from the drug. It's a very simple equation those patients do not receive the drug and you saved half of these patients the cost of the drug.
We need more positive predictors, meaning ones that would tell us who would benefit, not just those who wouldn't benefit, to continue improving the likelihood of these agents becoming cost-effective. Right now, despite all the analysis that we see and hear about, it's very difficult to make sense out of these analyses.
CALGB-0405 had a cost analysis integrated into it. It's relatively rudimentary, but it gave us a good reflection of what cost may look like in a patient receiving either chemo plus siltuximab or chemo plus bevacizumab. It did seem like chemo plus siltuximab was more expensive than chemo plus bevacizumab, and at least from the authors of the study the recommendation was that chemotherapy plus bevacizumab may be less costly and should be the preferred first-line therapy given that there is not much difference in terms of survival.
Unresectable Colon Cancer: Case 2
52-year-old woman newly diagnosed with metastatic CRC and is genotyped as part of her initial work up.