Long-Term Therapeutic Strategies in Colorectal Cancer

Transcript:John Marshall, MD: Let’s shift gears one more time and talk about downstream treatments—metastatic colon cancer after initial lines of therapy, through maintenance. And, of course, we’ve got more treatment choices in this refractory space; we’ve got new medicines, new side effects, and new data. Johanna, let me first get to you. I know you’re a major referral center in your part of the country. What percentage of patients are getting to this third-line in your world?

Johanna Bendell, MD: I think that more and more patients with colon cancer, given how good the treatments are up front, are making it to third-line therapy. Now, I’m just going to give my own biased estimate, but I would say it’s 70% to 80%.

John Marshall, MD: Tony, the average age where you live is like 90. Are you seeing an older population that does make it?

Tanios Bekaii-Saab, MD: Yes. Actually, interestingly, we do have a lot of older patients, and we have a number of younger patients. It’s, again, a referral center from across the western part of the country, so we see all of them. But, yes, even the older patients are making it to third-line. And I’d say 70% to 80% is probably the right figure. Now, again, we do have a skewed patient population across all our centers because we are a referral center, so you’re more likely to see the patients that are going to make it to the third-line.

John Marshall, MD: Who’s the patient, Alan, that’s not going to make it?

Alan P. Venook, MD: Well, the patient who’s not going to make it is a patient with peritoneal disease. Women with right-sided peritoneal in metastatic disease do very poorly. Again, this gets to those molecular subtypes, which I think will help define that. Unfortunately, we know that right off the bat. The BRAF-mutant patient, the patient with a BRAF mutation, is very unlikely to get to that point. And so, for the larger portion of patients, I’m not sure it makes a lot of difference what order you go in what treatment because these patients tend to have disease that responds and you get good periods of time even with holidays, which we can build in. But I think the patients with peritoneal disease are usually the patients who do very poorly.

John Marshall, MD: In pancreas cancer, we see a lot of what I’ll call, “therapeutic nihilism,” where people say, not necessarily from oncologists but from their primary care doctor, something like that. Is anybody seeing any of that here, an older patient where they just burn out, they’re okay, but don’t want it? Johanna?

Johanna Bendell, MD: Rarely.

John Marshall, MD: So, it’s not so much in this disease compared to the other. Tony?

Tanios Bekaii-Saab, MD: It’s a different disease. Again, they have the sense that they’ve responded to 1 line or 2 of therapy, and they went for a while. You might frame it just a little bit differently than the pancreas cancer patient. Again, most patients do search on the Internet, and they tend to think that pancreas cancer is a disease that is overwhelming, will take all of them, and they have this nihilism. On the other hand, with colon cancer, they see a different story. So, it affects them and how they view their future therapies differently.

John Marshall, MD: In a patient that you don’t think is going to go to resection, do you begin your first visit or early visits talking about these lines of therapy and set that stage for patients, Alan?

Alan P. Venook, MD: Well, what I do is I say, “We’re going to follow the bouncing ball.” You’re going to follow the disease. I don’t really talk about lines of therapy; I talk about a strategy. I tend not to start with FOLFOX because you’ve often burned that. If you go 6 or 7 cycles, a patient gets neuropathy. Then, in fact, you probably can’t revisit that or be hesitant to revisit it. So, we start with FOLFIRI, on average, but I talk about strategic moves. I will often, if a patient is doing very well on FOLFIRI, let’s say, go to every 3 weeks or every 4 weeks. I just try to keep the patient going. With high-volume disease to begin with, I might not give them a holiday per se. But we do, early on, talk about the strategy, which is don’t write the dates in their calendar in pen, write them in pencil, because I don’t. One of the most striking things to me is how many patients will come to me after 12 cycles of FOLFOX or 12 of this. If there’s a magic number, I think we avoid that. The other trick is to avoid the toxicities that can be devastating—steatohepatitis. Patients who get too much chemotherapy, some of them will develop fatty liver and you may get a big spleen. We very much play it by ear and watch the patients. If a patient says they’ve got a wedding to go to at such and such a time, then that’s what we build around. We want to have them chemotherapy-free for that period of time. And I think with the very effective therapies, in many of them, we have that luxury. We should be able to do that.

John Marshall, MD: So, the really important point—there are many that you made—is that frontline strategy needs to, in some way, have the downstream in mind. That if you burn them too much in the beginning, you’ll never get there. Is that right?

Alan P. Venook, MD: Absolutely.

John Marshall, MD: We all, I think, use “marathon race strategy” as the terms that we use with patients. Agreed?

Johanna Bendell, MD: Absolutely. And also, I think patients, they need to hear a few times, especially when they’re first diagnosed, that this is going to be a chronic treatment. I have so many patients that ask, “Okay, am I done?” You want to tell them that we’re going to build in holidays, but it’s the marathon.

Transcript Edited for Clarity