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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®: What are some of the treatment options for patients with metastasis, whether it occurs in the brain, lung, or liver? What will influence your treatment decisions? Which types of cases in patients with metastatic cancer will pose limitations to targeted therapy?

Paulson: As it relates to targeted therapy, I don’t think the picture is very clear—we are getting mixed messages from different trials. Some of the EPOCH data would suggest that using an EGFR inhibitor led to a trend in reduced survival in patients who were planning to undergo surgery in any operative setting, whereas other data suggest that higher response rates improve resectability outcomes. So, there are mixed data regarding the efficacy of targeted therapy in the planned surgical patient. 

How does that affect my decision? If I’m looking at some of these data and I know that they’re surgically resectable up front, and the patient has synchronous disease and an isolated liver metastasis that needs surgery, I would actually treat that patient with just chemotherapy up front; I don‘t necessarily apply any targeted therapy in addition to it. We tend to try to abbreviate the amount of systemic therapy that these patients get, to limit significant toxicity to the liver as they’re going to undergo liver resection. In lung, where you’re getting less toxicity from a lot of the chemotherapeutic agents, there’s certainly a lot more flexibility. Frequently, I’ll treat those patients with a VEGF inhibitor as well, but there are much less data to guide physicians around targeted therapy selection for lung metastasis protection. It’s a less common scenario, and therefore, it’s a lot less compiled.

Right now, as far as choice of targeted therapy for a resectable patient, I don’t think there are enough data to guide management; it has to be taken on a case-by-case basis, looking at the subtotal of everything. Is the tumor left-sided or right-sided? Should we be changing our tune on how we use targeted therapy based on that? I don’t know. I don’t have a specific algorithm. I tend to treat these patients who I know are going to go to surgery with chemotherapy alone up front. In this case, the use of targeted therapy is based on very specific clinical indicators. It’s not possible to have an algorithm for that; it’s a complex approach.
AJMC®: How does some of the uncertainty there potentially leave the door open for differences between specific agents within targeted therapy classes, if at all? Are there any possibilities there, in the future, for finding more specific populations that are appropriate for a given treatment, or do you think it’s more likely that we have to take a more pragmatic approach now, and that will continue to be the case? 

Paulson: I think, hopefully, we will eventually find the right population. That’s where I think we need to head with it. Which left-sided and wild-type tumor with an isolated hepatic metastasis is really going to benefit from an EGFR inhibitor to make them a suitable resection candidate? We need to nail down the genetics of it. We have conflicting data from multiple different studies that have been done over the past number of years. I think it’s going to be a matter of figuring out a better profile of these patients, and having those data so that you can make sound decisions. For now, we just have to take it on a case-by-case basis, trying to see what’s best for that patient. A lot of the choices of agents can be dictated by patients who know what their toxicity profiles are and what they could handle and tolerate on a day-to-day basis. You never know when you’re going to run into a patient who will absolutely not tolerate losing their hair or getting a skin rash, and then all of a sudden the FOLFIRI plus cetuximab combination is out of the question. 
AJMC®: In terms of choosing therapy, it sounds like there are a lot of variables, not least of which is the patient’s preferences and expectations. How you go about setting expectations for therapy for patients within the metastatic setting?

Paulson: It’s a challenging thing, because even patients who you do get to resection have a very high recurrence rate. Someone who will have an isolated liver lesion removed along with their primary tumor, they have metastatic disease, and especially if that’s showing up right at the time of diagnosis, even with a complete resection, the chances of recurrence are still more likely than not. That’s challenging because, if a patient is going to be going through a major amount of toxic chemotherapy followed by an exceptionally large surgery, you’re at least hoping that you can get to the point where you’re not going to have any cancer left in the body. So, the question becomes: How do we manage those expectations? We try to be as open and honest as we can, and then try to put that aside and go for as big a win as we can possibly try to get out of a tough situation. For the most part, that works. I think as soon as a patient hears that they have stage IV cancer, they realize what they’re up against and they also don’t want to get so aggressive that all quality of life is completely stripped, and that can happen. So that requires frequent check-ins and reassurance, but some people develop pretty debilitating neuropathy and skin rashes, with chemotherapy and targeted therapy. In addition, surgical morbidity is certainly not small if they’re having a large liver resection. 

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