Therapeutic Strategies in Metastatic Colorectal Cancer - Episode 9
Transcript:John L. Marshall, MD: Let’s talk a little bit about maintenance, because we all probably have different recipes. I know mine is the correct recipe, but you all could share your other choices on what you like. I know people do everything from nothing, a pure holiday, to a little capecitabine, to bevacizumab alone, to a combination of capecitabine/bevacizumab or 5-FU/bevacizumab. Tony, I’ll start with you. A regular old patient not on a clinical trial, 4 to 6 months or whenever, what’s your regimen?
Tanios Bekaii-Saab, MD: This is where it’s very, very important to include the patient in the discussion, and the patient's preferences are important. Ultimately, this is a palliative setting. We’re talking 2 or 3 months added if you do this or that. Ultimately, those patients are going to succumb to their disease at some point, and having a time for toning down the regimens or maintenance or even a complete break is not unreasonable. That discussion is cognizant of patient preferences, but also if the patient, for example, had a complete response, which about 9% to 10% of our patients do have a complete response, I’m actually inclined to go to a maintenance regimen for 2 to 4 months.
John L. Marshall, MD: What do you use?
Tanios Bekaii-Saab, MD: Infusional 5-FU, bevacizumab, or capecitabine/bevacizumab, either/or. And then if everything continues to be controlled, many times I give patients a complete break and just monitor them and restart the same regimen. I tend to have a trigger finger, whether it’s FOLFIRI or FOLFOX after 4 to 6 months to get rid of the oxaliplatin or the irinotecan and just go on a maintenance. And then the holidays are sugar on top.
John L. Marshall, MD: I use the CAIRO-3 approach, a chronic low-dose capecitabine, Q3 week bevacizumab is often what I do. Yes? You like that recipe?
Johanna Bendell, MD: Yes. I have trouble, though, with getting the copays, getting capecitabine for the patients. That throws a wrench into things, so I tend to start with the infusional 5-FU and then push the capecitabine later.
John L. Marshall, MD: What do you like?
Richard Kim, MD: I follow the CAIRO-3 data you mentioned. I use capecitabine and bevacizumab. There are a lot of data out there after my study, but out of those, the CAIRO-3 has probably some of the more robust data. I use capecitabine and bevacizumab after 4 to 6 months, all depending on how the patient is responding. If the patient responds after 4 cycles, after 4 months, I try to milk it more, give more chemotherapy to see if I could get down a further reduction of tumor. But, otherwise at the end of 4 to 6 months, due to neurotoxicity, eventually you have to change over to some kind of maintenance therapy if useful.
John L. Marshall, MD: The trick for me is that it’s our fault when people get neuropathy, in some way, pulling that trigger. What do you guys like to do?
Charles S. Fuchs, MD: You mentioned the CAIRO study and you talk about the idea of stopping everything. I look at that data and say you’re going to reduce survival if you stop everything, maybe not enough, maybe it doesn’t matter, but it is less.
John L. Marshall, MD: It’s double, right? The progression-free survival is 4 versus 8 months. 8 months is a long time, right?
Charles S. Fuchs, MD: It is. I certainly stop the oxaliplatin, the irinotecan. I don’t particularly encourage them to stop everything. Certainly, if they want to take a trip to Hawaii and they want an extra few weeks, fine. But, in terms of genuinely stopping all therapy, I tell them that the data we have in those comparisons of maintenance therapy does suggest there’s a better outcome if you do some measure of maintenance.
John L. Marshall, MD: The hardest question today we face is stage IV, no evidence of disease. We’ve already confessed that we cure some of them, but not most of them. We’re going after funky lesions here and there. To me, is this maintenance? Is it adjuvant? Do we leave them alone? I don’t think there’s a right answer. You get to go first, Richard. What do you do in this setting?
Richard Kim, MD: A case where, you give chemotherapy, the patient goes under radiographic CR by PET scan or CT scan. There’s definitely data from MD Anderson series when they go back and they biopsied those samples, about 80%-90% still have viable cells in there. I don’t think CR from CT scan, PET scan means cure.
John L. Marshall, MD: Well, what about resected?
Richard Kim, MD: After resection and after patients have no evidence of disease, I agree there’s no data what to do afterwards.
John L. Marshall, MD: 4 liver lesions, resected, CEA-3. Went from 800, 3 post-operative, scan negative, 4 liver lesions, synchronous liver metastases, so a high-risk relapsed patient, right?
Richard Kim, MD: I give almost like a stage III patient, give 6 months of FOLFOX and then I stop afterwards.
John L. Marshall, MD: So you give adjuvant therapy.
Johanna Bendell, MD: Yes.
Richard Kim, MD: Yes.
John L. Marshall, MD: Adjuvant?
Tanios Bekaii-Saab, MD: No.
John L. Marshall, MD: Nothing? What do you do, watch them?
Tanios Bekaii-Saab, MD: I’m not sure that you’re actually going to change the course. And the data from the EORTC study and the EPOCH, too, does not really confirm a significant survival advantage. If anything, a slight PFS advantage at 3 years doesn’t translate into an OS advantage for the clearly resectable.
John L. Marshall, MD: So why don’t you give maintenance?
Tanios Bekaii-Saab, MD: Why would you?
John L. Marshall, MD: I don’t know. It feels right to me. It’s what I would give if it was my disease.
Tanios Bekaii-Saab, MD: I can’t say this is the wrong approach, the same way I can defend my approach is where we’re saying there’s a lack of good data. So either/or is right. This is where your clinical experience, your clinical acumen trumps data because the data is really not solid one way or the other.
Charles S. Fuchs, MD: I give adjuvant. I agree with you, Tony, that the EORTC study, which looked at giving FOLFOX in conjunction with hepatic resection, didn’t show an OS benefit. The problem is it’s a small study. They were never going to get a survival benefit. There are not enough patients in the trial. There’s certainly a trend in terms of disease-free survival. I routinely give adjuvant.
Transcript Edited for Clarity