Tumor Locations in CRC

Transcript:Alan P. Venook, MD: The anatomy of the colon, this is something we’ve known. For example, gastroenterologists, for years, have described these flat serrated polyps in the right side of the colon. They are not in the left side, but in the right side. They’re biologically different. I think the main thing we have to realize is that it’s not a uniformed population of cancer cells. For the moment, what I believe is we’ll have to say studies will put patients with right-sided cancer in one study, patients with left-sided cancer in another. I hope that isn’t for too long, though, because I would assume we will figure out what the features of the right and left side are that are dictating outcomes.

I think, anatomically, there are other ramifications. It’s been fascinating. There’s been an argument in some health-providing organizations about doing sigmoidoscopy or colonoscopy. When we’ve now clearly shown that right-sided colon cancer is just different than left-sided colon cancer, how in the world would you only do a sigmoidoscopy? Because they’re just different entities, it makes no sense to me. It’s like doing a right mammogram and not a left mammogram. Looking at the left colon doesn’t tell you anything about the right colon. I don’t know if that’ll have ramifications there, but it should.

And then the other thing I believe is that our approach, in terms of our goals of therapy, may now be very different. Patients with right-sided cancer may be a much heavier lift, to be able to cure them, given their innate prognosis. These are all factors that will go in. It doesn’t mean that I’ll do something dramatically different for the patient who shows up on this Wednesday, but I’ll be thinking of it. As one of my colleagues says, “I’ll think of RAS, RAF, MSI, and which side.” And hopefully at some point, we’ll figure out what tumor side represents.

Do we test patients with right-sided cancers? Why would we do that if we’re not going to use the cetuximab? Good question. And I think right now, I’m not sold on knowing all the answers on the right side so I would still check. There was one observation in our study that was really hard for me to understand. It absolutely twists us up into a pretzel—and that is because we had a pre-amendment group of patients who received cetuximab, even though they were RAS-mutant. We didn’t know that we shouldn’t be doing that. We had a couple hundred patients who we were able to analyze in terms of right versus left side.

Patients with RAS mutations and right-sided cancers lived 23 months. Patients with RAS wild-type, getting cetuximab on the right side, lived 16 months. So, the patients who should not be getting cetuximab lived almost 7 months longer than the patients we would give cetuximab to. It makes no sense and really tells us we don’t understand RAS very well. But that’s an idea; that gives you a handle on how we have to look at the disease now. A lot of the things we thought we knew, we don’t know. And in many ways, it’s almost back to the drawing board because we get into trouble when we have biases and we think we know what we’re doing. In fact, it’s a humbling, humbling process to figure out that maybe we don’t know what we’re doing. For this, though, we’re hoping to put together a big international consortium, put all of our data together, and see if we can’t really get clarity by doing that, as well, and we’re in the process of doing that. The most important dataset, a couple of important datasets, are from the CRYSTAL study, which is FOLFIRI with or without cetuximab and KRAS wild-type patients; it is very important.

Transcript Edited for Clarity