First-Line Treatment Options for mCRC


After a brief overview on first-line treatment options for patients with metastatic colorectal cancer, panelists highlight the role HER2 status plays in the selection of novel therapies.


Kristen K. Ciombor, MD: That was a great discussion about ctDNA [circulating tumor DNA], NGS [next-generation sequencing], and how we decide to use these assays. We’ll talk more about specific subgroups of patients with metastatic colorectal cancer [mCRC]. We have a lot of cytotoxic chemotherapy backbones and biologics. In the first line, we have a lot of options. For patients who have a biomarker that we can treat, and utilize for treatment in the first line, that’s 1 thing. But for the patient who has RAS wild-type disease, for example, we have many options on how to initially treat. When I think about it, I definitely keep in mind not only the biology, primary tumor “sidedness,” and some of the mutational status but also the goals and preferences of the patient. Because if a 30-year-old is healthy, you’re not going to treat them similarly to an 80-year-old who has a lot of comorbidities. They may not want the same treatment even if they were fit enough to receive it. It comes into play. We have a lot of factors that we need to consider. It makes oncology not only a science but also an art. You have to keep in mind a lot of things.

We also think about toxicities. That’s something patients are appropriately very vocal about—which toxicities they think are easier to tolerate than others. I’ve had patients who said, “I don’t want to lose my hair at all costs because I don’t want people to know what I’m going through.” [Others] say, “I can deal with a little neuropathy.” All those things are important, but we’re also starting to see how we have a lot more options in the first line because of molecular status. That brings back the point that we need the molecular data early in our treatment course, [as opposed to doing] FOLFOX [5-fluorouracil, leucovorin, oxaliplatin]and FOLFIRI [5-fluorouracil, leucovorin, irinotecan]and then figuring that out later. We’re also thinking about how many chemotherapy agents to use at 1 time, what combinations, and what type of biologics. That’s advanced in the last few years, even though we’ve had those same drugs for a long time. It’s important to factor in a lot of things, like primary tumor “sidedness” and molecular alterations.

Let’s talk a little about some of the different subtypes and how our therapies are changing. Dr Hubbard, how do we test for HER2 [human epidermal growth factor receptor 2]? We’re starting to catch up with our breast oncology colleagues. We’re not there yet, but we can learn from them. How do we test for HER2 in colon cancer? Who do we want to know about that information? In what types of patients?

Joleen M. Hubbard, MD:HER2-positive colorectal cancer occurs in 3% to 5% of patients, depending on the study you read. It’s enriched if you have patients who don’t have a RAS or BRAF mutation, and then it’s upward of 10% of patients. When you think about 150,000 new cases per year, that’s a significant number of patients who have HER2+ disease. We can detect it in several ways. The gold standard is immunohistochemistry [IHC], but we can also identify it with in situ hybridization as well as amplification when we get a next-generation sequencing panel. I caution people that when we use ctDNA, sometimes that can underestimate the prevalence; we have to be a little cautious.

This year at ASCO [American Society of Clinical Oncology Annual Meeting], we’re going to see a poster presentation from Andrea Cercek, who’s looking at how we test for HER2 positivity in colorectal cancer. It’s established very well for gastric cancer and breast cancer but not for colorectal cancer. They did a study from the patients from the MOUNTAINEER study, which was a study for HER2+ patients. Of the patient samples from that study, they looked at testing it via the breast cancer algorithm or the gastric cancer algorithm. Interestingly, they achieved 100% concordance between the 2 assays in the immunohistochemistry score. Either way was 99% concordance. That tells us we can probably establish a standard IHC test for colorectal cancer based on the HER2 algorithm or the gastric algorithm. It’s pretty important to get that established. A lot of pathologists are like, “Wait, there’s no validation for this test.” I’m happy to see that we’re moving forward with a validation.

Joel R. Hecht, MD: We’re already driving the pathologists crazy with PD-L1, sonot having a third standard is wonderful.

Transcript edited for clarity.

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