The Current Paradigm of Metastatic Colorectal Cancer


Johanna C. Bendell, MD: In the last few years, we’ve made significant advances in the treatment of patients with metastatic colorectal cancer. We have multiple new combinations that we use, FOLFOX [folinic acid/fluorouracil/oxaliplatin] and FOLFIRI [folinic acid/fluorouracil/irinotecan]. We have targeted agents like bevacizumab, cetuximab, panitumumab, and now TAS-102 and regorafenib. By using these combinations of therapies and sequencing therapies appropriately, we’re able to improve the survival of patients with metastatic colorectal cancer.

Before, when we just had 5-fluorouracil, we had about 12-month overall survival averages. But now, as we move patients through the progression of all the different potential regimens and agents they can get, we’re seeing survival of 3 years or potentially even better. We’re seeing that patients can also have improved surgical outcomes if they have potentially resectable metastatic disease. We’re seeing more cure in patients with advanced colorectal cancer.

The biggest thing we’re also doing is learning more about subsets of patients with metastatic colorectal cancer, including RAS wild-type versus mutant patients, BRAF-mutant patients, and patients with microsatellite instability [MSI] who may have different treatment options than others. It’s important that we know and classify the tumors that our patients have to make sure that we optimize their care.

Though we’ve made big advances for patients with colorectal cancer, we still can do better. We haven’t cured everybody. We haven’t bumped survival out past 3 years, and so that’s our main focus now. How can we bring new agents into play to improve outcomes for these patients? We’re doing better for the treatment for patients with metastatic colorectal cancer, but we still have a long way to go. We are able to cure some patients, we’re able to improve survival, but certainly to do better in terms of increasing survivals further or curing more patients is our ultimate goal. And right now, we’re at a time period where there’s a lot of research going on, looking into ways to improve survival for those patients with refractory disease.

Tanios Bekaii-Saab, MD: Colorectal cancer, as we understand it now a little bit more—and there’s a lot more to understand—is not 1 but multiple cancers, if we define it biologically or through molecular breakdowns. We know 1 thing: that the left and the right look different. The rectum looks a little different than the left; closer to the left, it transfers. Looking now at the left, we initially thought it looked more like the right. But even when you look at the molecular and genetic changes as you move across the right or the left, you also change your genetic composition regarding enrichment for some mutations versus others: MSI high on 1 part but not on the other part, BRAF mutations, or primary RAS mutations on the right side.

What we know is that colon cancer is a lot of different diseases, not 1. We at least know the role of RAS mutations. We’re starting to understand a lot more about the role of HER2 amplifications. We understand a little bit more BRAF V600E mutations. We also know what the non-V600E mutation may mean or MSI-high disease, and we’re learning more and more about FGFR, PIK3CA, and lots of others genes. We’re starting to understand a little bit more about the intricacies of molecular and genetic subtyping of colon cancer and what it will essentially mean for future targeting. We know what it means for current targeting, which is an evolution, but in the future, I foresee that colon cancer will be primarily defined by immunogenic, epigenetic, and molecular subtypes.

Transcript Edited for Clarity

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