Deciding on Adjuvant Therapy in CRC


John L. Marshall, MD: Thank you for joining us for this OncLive® global Peer Exchange® on individualizing treatment and improving outcomes for patients with colorectal cancer. Optimizing treatment in colorectal cancer is centered on understanding the biology of the underlying disease and working with other members of the multidisciplinary team to determine the best approach. The emergence of immunotherapy has brought additional tools to the current treatment landscape, and novel combinations are on the horizon. This panel of experts in gastrointestinal (GI) cancers will have a practical discussion regarding the various treatment modalities, provide an update on tumor-sidedness, and will review the latest data likely to alter clinical practice.

I am Dr. John Marshall, director of The Ruesch Center for the Cure of GI Cancers and chief of hematology and oncology at the Lombardi Comprehensive Cancer Center of Georgetown University Medical Center, in Washington, DC. Joining me for this panel are some of my best friends and really, really smart people: Dr. Johanna Bendell, who is the chief development officer and director of the GI Cancer Research Program at the Sarah Cannon Research Institute in Nashville, Tennessee. Johanna, welcome.

Johanna C. Bendell, MD: Thank you for having me.

John L. Marshall, MD: Right on this side of me is Dr. Cathy Eng, who is a Sophie Caroline Stevens Distinguished Professor in Cancer Research and professor in the Department of Gastrointestinal Medical Oncology at The University of Texas MD Anderson Cancer Center, in Houston, Texas. Cathy, welcome.

Cathy Eng, MD, FACP: Thank you.

John L. Marshall, MD: Back over here we have Dr. Michael Morse, professor of medicine, professor in the Department of Surgery, although he stresses he does not cut people open, and medical oncologist at Duke Cancer Institute, in Durham, North Carolina. Mike, welcome.

Michael A. Morse, MD: Thank you, John.

John L. Marshall, MD: And last but not least, from the far north, we have Dr. Dale Shepard, director of the Phase I and Sarcoma Programs and a medical oncologist at the Taussig Cancer Institute at the Cleveland Clinic, in Cleveland, Ohio. Welcome, Dale.

Dale R. Shepard, MD, PhD, FACP: Thank you.

John L. Marshall, MD: We’re going to start with earlier stage colon cancer. Johanna, I’m going to pick on you to start. You’ve seen the patient with early-stage disease. He or she comes to you in the clinic. You’re going to have a discussion around adjuvant therapy or not. Can you give us a sense of how you sort of decide and integrate decision making in adjuvant therapy?

Johanna C. Bendell, MD: The biggest piece of it is looking at the patients themselves. Have they recovered from the surgery? What’s the patient’s age? We have to look at comorbidities as well as think about the potential lifespan of this patient.

The next part is looking at the pathology report, of course, to see the T and N stage. You need to make sure that those patients have had the proper staging. I can’t tell you how many times I’ve had patients come in with the abdominal and pelvic CT. Then there’s this controversy between the surgeons and the medical oncologists—and there may even be controversy around the medical oncologists—regarding whether you need a chest x-ray versus CT.

John L. Marshall, MD: You’re in the Department of Surgery. What’s up with that? I’m seeing this all the time. We’re not getting chest CTs because the surgeons say it’s not supposed to be done. What do you think?

Michael A. Morse, MD: Well, the surgeon said they got it all, so they obviously don’t need it. No. At our institution, it’s pretty regular to get a chest, abdomen, and pelvic CT before people are operated on.

John L. Marshall, MD: We’re often coming back and picking up that chest CT in the postoperative setting, right? I didn’t mean to interrupt, but I think it’s a big deal.

Johanna C. Bendell, MD: Exactly, as well as the pre-operative CEA (carcinoembryonic antigen), so you have something to base things off of. And then, working on vascular access. If this patient is a stage 3 patient or a high-risk stage 2 patient who’s likely going to require some kind of adjuvant chemotherapy, we need to think about making sure that patient has appropriate vascular access. There’s a lot of discussion now that we’re using more CAPEOX. I know we’re going to talk about using a central catheter in the adjuvant setting. Still, giving oxaliplatin peripherally is not so much fun.

John L. Marshall, MD: Is anybody doing that? Are you giving oxaliplatin peripherally?

Cathy Eng, MD, FACP: It’s not even allowed at our institution.

John L. Marshall, MD: It is not allowed, but I see a lot of it being done. “It’s only going to be a few cycles. It’s all good.” So, getting some vascular access. Let’s sort of carve out stage 2 cancer. Let’s be a little controversial, at first. Dale, maybe I’ll pick on you. If you’ve got a stage 2 patient, what are some of the things that you’re factoring in, to decide who gets treatment and who doesn’t?

Dale R. Shepard, MD, PhD, FACP: I really factor in the traditional things. If it’s a stage 2 patient, if they have high-risk factors, if they had perforation, if they have sort of a larger tumor, if they have obstruction at presentation, they’re kind of the big things.

John L. Marshall, MD: Then you lean more toward treating those patients?

Dale R. Shepard, MD, PhD, FACP: I lean more toward treatment instead. I think the discussion is about the fact that they are less likely to have a recurrence. And so, are we going to put them through treatment when they might not need it?

John L. Marshall, MD: I always wonder about this. We say, “high risk.” You mentioned it, too—about high-risk stage 2 patients. Yet those were the patients that were in the adjuvant trials, right? And yet, we don’t really show benefit with the addition of oxaliplatin in that group. The data say one thing and our bias says the other. Are you giving oxaliplatin in that high-risk patient?

Cathy Eng, MD, FACP: For high-risk stage 2 cancer?

John L. Marshall, MD: Yes.

Cathy Eng, MD, FACP: I largely just have the discussion with the patient. I rarely actually give chemotherapy to a stage 2 patient, unless they have evidence of perforation.

John L. Marshall, MD: For an 8-cm, cecal lesion? T3, N0, 0 of 12, 40 years old?

Cathy Eng, MD, FACP: No.

John L. Marshall, MD: No. Does anybody say yes on that? Maybe?

Johanna C. Bendell, MD: Obstruction, poorly differentiated?

John L. Marshall, MD: No, just a big old cecal thing.

Cathy Eng, MD, FACP: Basing it all on size?

Johanna C. Bendell, MD: Oh, you can’t base things on size, John Marshall.

John L. Marshall, MD: There you go. I know, but you see these huge masses.

Johanna C. Bendell, MD: That’s true.

John L. Marshall, MD: Node count still matters, right?

Cathy Eng, MD, FACP: Definitely.

John L. Marshall, MD: Yes. And so, maybe not enough nodes lean one way or the other?

Johanna C. Bendell, MD: The proper surgery and the proper surgeon.

John L. Marshall, MD: Yes.

Cathy Eng, MD, FACP: You mentioned a right-sided tumor in that setting. That’s when you want to test them for MSI—high, right? So, that’s even more reason not to give treatment.

John L. Marshall, MD: We’re going to do molecular testing. How about Oncotype? If I’m a breast patient, I’m getting that, right?

Michael A. Morse, MD: For the right patient. For people that really need to be nudged in one direction or another, it’s a good test—if people know how to use the information from it.

John L. Marshall, MD: So, you are doing it sometimes? I’m always confused about when I get one of these. I don’t think I’ve ever really ordered one.

Cathy Eng, MD, FACP: Or the interpretation of it.

John L. Marshall, MD: How to, then, apply it. It is being done, and many surgeons are ordering it, too. It comes to our chart, when we’re sitting there. What are we going to do with it? You mentioned MSI, Cathy. Does every colon cancer patient need MSI testing?

Cathy Eng, MD, FACP: Every colon cancer patient should be tested.

John L. Marshall, MD: Stage 1 through stage 4?

Cathy Eng, MD, FACP: Correct.

John L. Marshall, MD: Every single one, right or left?

Cathy Eng, MD, FACP: I think everybody should be tested.

John L. Marshall, MD: OK. Is everybody OK with that?

Johanna C. Bendell, MD: Yes.

John L. Marshall, MD: Let’s say that you’ve done that. We’ll be very specific. In a stage 2 patient, do you have to know MSI before doing any decision making on adjuvant therapy?

Cathy Eng, MD, FACP: You don’t have to know, but I think it’s very helpful. That will really tell you that the patient doesn’t need adjuvant chemotherapy. They have a good prognosis.

John L. Marshall, MD: So, before starting it, you would want to know, probably? Before initiating, if you were leaning toward treating somebody? What do people think about MSI and oxaliplatin overcoming whatever negatives from the other data, Johanna?

Johanna C. Bendell, MD: Well, it does appear that there is 5-FU resistance and not necessarily platinum resistance. So, if you have a patient for whom you’re thinking about high-risk stage 2 disease, and you’re thinking about stage 3, and the patient is microsatellite instable, FOLFOX is still a standard of care. That’s a very important point to make.

John L. Marshall, MD: Now there are data that actually show that FOLFOX looks the same whether you’re MSI or not. In stage 3 disease, if you were leaning toward giving FOLFOX anyway, then maybe MSI doesn’t matter?

Johanna C. Bendell, MD: That would be the one group of patients in whom it doesn’t matter. But you might want to know it in terms of risk of recurrence. You might want to know it in terms of looking for sporadic Lynch syndrome. I mean, like, for the first person that’s presented that might have Lynch syndrome, you’d be thinking about genetic testing.

Cathy Eng, MD, FACP: You might want to know it just in case they have recurrence, too.

Transcript Edited for Clarity

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