Metastatic Colorectal Cancer: Frontline Treatment Paradigm



Howard S. Hochster, MD, FACP: Today, I think the question of first-line therapy sets the stage for subsequent therapies. I would say most of the time, most of us are using FOLFOX [folinic acid (leucovorin), fluorouracil (5-FU), and oxaliplatin] plus bevacizumab as first-line therapy, but the question is if you should be using an anti-EGFR antibody first line for left-sided tumors. The CALGB/SWOG 80405 data didn’t really show superiority for that, but the study may have been too small. The European data are a little bit more favorable and statistically significant suggesting that you should use anti-EGFR antibodies on the left side. So that’s one situation where the practice in the United States and the practice in Europe are a little bit different.

I would say at the moment, I tend to still use bevacizumab first line and then save the anti-EGFR for later, because we know it works as well in subsequent lines as in first line. There’s no real particular benefit that we know of in giving it first compared with bevacizumab, and that was pretty well demonstrated in the CALGB/SWOG 80405 trial. Additionally, when you’re starting people with chemotherapy, they have to deal with all the skin toxicity a little bit, and it’s an extra burden on the patient. So, personally, I prefer to save that for subsequent line therapies.

Today, for first-line therapy of colon cancer, I think we’re mostly using FOLFOX or—for the higher risk patients, like BRAF-mutated patients—even FOLFOXIRI [folinic acid, 5-FU, oxaliplatin, and irinotecan]. I’ve been using that more and more for younger patients, for patients I want to get to liver resection or for patients who have BRAF mutations. I think in general, it’s tolerated pretty well, certainly no worse than FOLFIRINOX [folinic acid, 5-FU, irinotecan, and oxaliplatin] for pancreatic cancer patients. A lot of the Europeans tend to use FOLFIRI [folinic acid, 5-FU, and irinotecan] first. Some of our American colleagues also suggest we should use FOLFIRI first and not introduce the problem of neuropathy in first-line therapy, so that’s also another option. There’s really no major reason not to give FOLFIRI first line. I think it’s more that we’ve set up our paradigms that way. Perhaps oxaliplatin could come back and be used later, too. So, I think there’s some benefit to giving it first and then coming back after having had FOLFIRI for a while.

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