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

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

AJMC®: Can you summarize how treatment of colon and colorectal cancer begins with surgical therapy, progresses to surgery with chemotherapy, and then also includes, potentially, targeted therapies? 

Paulson: In general, the management of local disease, like early-stage cancers, involves a combination of surgery and possibly chemotherapy, depending on exactly what point it’s at. Targeted therapy up to this point has no role in that setting whatsoever. So, early-stage curable disease is managed with a combination of surgery and chemotherapy. With metastatic disease, it depends on several factors, but often we manage it using a combination of chemotherapy and surgery. The role of targeted therapy in curable disease often includes management of, for instance, cancer that spreads into the liver and/or lungs. It is a bit unclear, but certainly multiple different targeted therapies are integrated with that as well
AJMC®: What is the current role of genetic testing in colorectal cancer? Which tests are done clinically?

Paulson: At present, the standard of care would be testing for mutations such as KRASNRAS, and BRAF. There are a lot of other tests that are done in multiple different centers, and personally, I often perform many of those tests. However, in colon cancer I actually tend to keep that fairly limited and try to be mindful because a lot of the therapeutic implications are really summed up in that first KRASNRASBRAF analysis. For patients who require more expanded options right up front, often I will do a focused panel of HER2 [human epidermal growth factor receptor 2] analysis and a couple of additional molecules as well, just to try to get a better genetic profile. But for the first pass, it is going to still start with what the NCCN [National Comprehensive Cancer Network] guidelines say, and standard of care. 

In colorectal cancer, from the payer perspective, coverage generally does not extend beyond KRASNRAS, and BRAF testingParticularly with colorectal cancer, we tend to get a lot more questions if we are trying to do a more expanded panel up-front. As a result, I tend to stick to the standard of care first, if it is ordained by NCCN, and then move forward from there. For patients who understand the potential financial implications of expanded genetic analysis, I am actually much more inclined to do that than look at HER2 analysis, as well as a couple of other choice molecules as well. There are still cost implications to the patient, and they have to be willing to accept that they may be financially liable for a lot of extended molecular testing. I, personally, do not think it is necessarily right that we are getting too overprotective of a couple of gene samples in a disease that is exceptionally costly. At times, having a genetic profile of a patient with cancer is extremely useful. At present, it is not necessarily something that is always recognized by the payers. 

AJMC®: When it comes to use of various chemotherapeutic regimens, when you are choosing a regimen and you are choosing candidates for surgical therapy, what kind of criteria do you use? What are some of the interesting edge cases in terms of selecting patients for different modes of treatment?

Paulson: Therapy for colon cancer has gotten so much better, and appropriate selection of patients has improved significantly enough. The only edge cases are patients who are either unwilling or physically unable to tolerate combination chemotherapy. These are generally elderly patients who are well into their late 70s and early 80s, who don’t have a lot of functional reserve, and they may be jeopardized if put on combination chemotherapy. 

The other edge cases that you will run across are patients who are just flat out unwilling to undergo chemotherapy. They’ve either had family members who’ve gone through it, they’ve seen toxic effects from it, or they’re just interested in different holistic approaches. These would also be patients who I would not consider to fall under the standard treatment algorithm. However, this can be a little challenging because, from a payer perspective, you’re not going to be able to just do whatever you want. You still have to follow some degree of established treatment protocol. Those tend to be a little more challenging if patients are simply not interested in following standard of care. 

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