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Perspectives in the Treatment of Colon Cancer with Leonard Saltz, MD

Perspectives in the Treatment of Colon Cancer with Leonard Saltz, MD

AJMC®: In terms of genetic testing, how important is it to get genetic testing early on in the disease?
Saltz: We rarely have genetic testing back before we initiate first-line therapy because the turn-around time takes a several weeks. I don’t think that matters because I don’t believe the data supports the use of first-line EGFR inhibitor in RAS wild type patients. That’s the only information that would guide a first line decision. I published a piece few years ago, in JAMA Oncology on this topic, where it pointed out that the largest clinical trial on the topic is the intergroup 80405 study, which directly looked at front-line chemotherapy with either cetuximab or bevacizumab in RAS wild type patients, and it did not show a meaningful difference in terms of outcome. But the toxicity of EGFR agents is very difficult for people to tolerate front line. At the doses that are routinely used are twice the cost, so I don’t see a reason why I would want to use these upfront. I think that we need to be obtaining the molecular information on mismatch repair status, KRAS, RAS, and BRAF when we initiate the care for the patient with metastatic disease. I would emphasize that thus far, we don’t have any role for looking at KRAS, NRAS, BRAF, or any other genetic mutations in stage I, II and III disease. So, I am often puzzled when somebody refers a patient to me and says they have stage III KRAS mutated colon cancer, I wonder, “Why do we know that?” To me that’s not an appropriate test to have sent. It is only in the setting of metastatic disease that the RAS information becomes relevant.
AJMC®: What is the role of potential adverse events with various treatment options in selecting appropriate therapy for each individual patient?
Saltz: We have to think carefully about that one. We have reasonable choices. For example, front-line therapy is often based on either irinotecan-containing or oxaliplatin-containing regimens. The toxicities are different, while the effectiveness is very similar. The neuropathy of oxaliplatin would be much more of a problem to some people and less 
to others. Irinotecan is much more likely to cause alopecia than oxaliplatin. That may be irrelevant to some and very important to others. So, talking with patients can allow us to individualize treatment. Bevacizumab, which we often incorporate into the first-line regiments, is a higher risk in people with significant cardiac disease, and don’t want bevacizumab on board in patients who might need urgent surgery. Those are settings where knowing the side effect profile of the drug might cause me to be more or less likely »
to use it. Cetuximab and panitumumab are only going to be effective in patients who get substantial skin rash. The rash does not guarantee the activity, but the absence of rash virtually guarantee that there isn’t activity. We need to have the patient prepare for that and discuss in terms of that relative risk and benefits, and whether that is the right drug for that individual.
AJMC®: What are other areas that are important for managed care, and if you could send one message to the managed care, what would that be in terms of the treatment of colon cancer?
Saltz: One has to be aware that we are long past the days where one size fits all. We need to individualize care based on the overall medical and psychological condition of the patient, who they are, what their preferences are, what their medical comorbidities are, and to some degree, what the molecular characteristics of their tumor are in terms of mismatch repair status, RAS mutation status and BRAF mutation status.
AJMC®: What do you see is the future of treatment in colon cancer, and how do you see it changing over the next 5 to 10 years?
Saltz: I hope that some of the newer immuno-therapeutic approaches will show some benefit. It is exciting that immuno-oncology has transformed certain previously resistant tumors, and I hope that we will be able to bring meaningful benefit with immuno-oncology to the majority of the patients with metastatic disease, specifically those with micro-satellite stable disease. It’s important to realize that we are not there yet, so that’s why I’m hoping the clinical trials will deliver to use over the next 5 years.

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