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Perspectives in Targeted Therapy for Colon Cancer with Scott Paulson, MD
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Perspectives in Targeted Therapy for Colon Cancer with Scott Paulson, MD

AJMC®: As far as use of chemotherapy in combination with targeted regimens, how do you make treatment decisions about using those treatments in combination, and how are those discussions coordinated with patients? What are challenges from a managed care perspective in terms of using targeted treatments?

Paulson: Insurance is not as much of an issue in coverage of targeted therapy as long as you’re following established guidelines, provided that you’re not treating KRAS-mutant patients with EGFR inhibitors or doing anything that’s considered inappropriate treatment. I don’t think you frequently run across insurers flat out refusing to pay for targeted therapies that are more expensive. Some very selected, very managed plans will only allow you a certain amount of cetuximab every 3 months. I have seen that, where you have to be judicious about your use of it. That‘s exceptionally rare, though. I would say as long as you’re following standard procedures, you don’t really run into many challenges with the payers. FOLFIRI [folinic acid, fluorouracil, and irinotecan] is actually very cheap, FOLFOX [folinic acid, fluorouracil, and oxaliplatin] is also fairly cheap relative to the targeted therapies, but a little bit more expensive. 

So, getting and securing combination chemotherapy is dependent on the targeted therapies, and is very, very rarely a challenge. But I don’t tend to run into that much of an issue except from exceptionally managed plans when using targeted therapy, provided you’re following guidelines.
 
AJMC®: When you are selecting, for instance, an EGFR inhibitor or a VEGF inhibitor, how do some of the indications for use of those treatments vary? For instance, panitumumab varies in its indication for use versus cetuximab: Are there any limitations that you run into as far as the specific indication for the product?

Paulson: You mentioned very specific examples. Essentially, [these are] what I would view as similar medications. There are certainly established medical data in different settings for each of them. When I look at those data, I find that each drug could essentially be interchanged in most clinical settings. I feel that the payers certainly agree with that as well. They are both extremely costly. So, that choice is often just dictated by whatever is most appropriate for the situation. 

Panitumumab and cetuximab are similar enough drugs that I feel like a lot of the evidence in both of their settings can be applied to either drug. I think the VEGF inhibitors are a little bit more challenging, just because there tends to be a much broader difference in price. Ramucirumab is a much more expensive drug at present, and bevacizumab and ziv-aflibercept are less expensive. So, I think focusing on those different drugs is still important, certainly when you’re looking at the second-line setting

When it comes to choosing the differences between the VEGF inhibitors that are used in combination with chemotherapy, that’s a little more important than choosing between the 2 or choosing between the 3. Whereas, when it comes to panitumumab and cetuximab, their prices do vary somewhat, and I think it’s better to go with a more cost-effective option, certainly. But it’s less of a clinical piece than, for example, the difference between ramucirumab and the rest. 
 
AJMC®: How do some of the differences in the trials with targeted therapies factor in to making a decision as far as selecting patients for a specific treatment? Or is it more of a selection based on general classes?

Paulson: If you had asked me 3 years ago, I would have said that you have to follow the cookbook recipe to an absolute fine point, and that if it’s not specifically provided for by the indication, then you absolutely cannot vary it. I’m starting to call that into question. I’m not saying that I’ve certainly changed my perspective on it. I like to follow the evidence as it is displayed. However, we’re running into situations where the cost of drugs continues to increase and we need to be mindful of finding more cost-effective options, and be able to integrate them into patient care in what we would feel is an appropriate way, even if it doesn’t necessarily meet the indication. So, I’d say that that’s evolving.

Another thing that’s evolving as far as choice of targeted agents and how we sequence everything is right-sided versus left-sided data, where I don’t think the entire molecular picture of the tumor is quite complete yet. I hope to see further data coming out on that, which will probably be able to help us choose patients extremely effectively right from the start, and treat them in a sequence where we can expand survival. We’re still trying to figure out exactly which patients are best served by an upfront EGFR inhibitor versus a late EGFR inhibitor, and how long we can keep people on vascular endothelial growth factor inhibitors. These questions, I don’t think, are perfectly answered yet, but I do believe that they’re going to continue to evolve. Throughout all of that, we have expensive drugs that are being tagged on to therapy at each point. Insurers are trying to make smart, sound decisions about how to prescribe the low-cost targeted therapy in a reasonable way, even if it doesn’t stick exactly to what we’ve done in the study.
 


 
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