Determining Appropriate mCRC Testing Strategies

Dr Ciombor provides her insight on determining appropriate testing strategies for patients with metastatic colorectal cancer.

Kristen Ciombor, MD: When a patient has metastatic colorectal cancer, how do I perform the molecular testing? What goes into my consideration? There are certainly genes of interest that are actionable. Things like KRAS, NRAS, BRAF, MSI [microsatellite instability], deficient mismatch repair, and HER2 are all important in our guideline-directed biomarker testing. However, some oncologists will do piecemeal testing for all of those genes. But as those genes increase in number, it becomes difficult from both a tissue point of view and an efficiency point of view to do that in a piecemeal fashion.

These days, I do a next-generation sequencing platform that we have a contract with institutionally, and that’s changed over the years. Basically, that will give me efficient multipanel information, not only the actionable alterations but also things that may be important in the future or that I may have clinical trials for—things like PIK3CA or others that we have clinical trials for and will likely become important or treatment options for patients in the future, at least in clinical trials.

It’s important to know from the outset what these patients have. Even though tissue isn’t typically an issue for colorectal cancer in terms of the amount that we can get—we can often get good liver biopsies—we have to be thoughtful in how we test for this and make sure that we’re utilizing the tissue appropriately and efficiently. Next-generation sequencing largely does that. There are occasional times when I’ll send in-house testing—such as mismatch repair testing, BRAF, or HER2—while I’m waiting for the larger next-generation platform to come back. But those cases are a little rarer. For most patients, next-generation sequencing platforms make the most sense.

We’re starting to learn the clinical utility of earlier use of biomarker testing. As I mentioned before, we used to use a lot of this information in the third-line setting or beyond in patients with refractory disease. Targeted therapy, things like anti-HER2 therapy, are often given based on our clinical trial use later in the course of a patient’s disease, but that may not always be the case.

There are often implications for what that status means for patients’ other therapies too. For instance, if I know that a patient has HER2-amplified colorectal cancer, I likely wouldn’t give anti-EGFR therapy in the first line because we know it’s less likely to work. There are a lot of potential implications for molecular testing and what those results may mean for patients. I find that doing that testing early in the patient’s course sets us up for success in terms of making sure that we can sequence the best therapies appropriately for the patients.

We’ve known that HER2 amplification in other tumor types has been important. As GI [gastrointestinal] oncologists, we have learned largely from our colleagues in breast cancer who have known about HER2 for a long time. In the GI oncology world, not only in colorectal cancer but gastroesophageal cancer, it’s an important target too. In metastatic colorectal cancer, it’s a relatively rare subtype. However, it shouldn’t be ignored, and it isn’t super rare once you look in the proper setting. We know that patients with left-sided disease are more likely to be HER2 amplified, and it’s more likely to be helpful as a biomarker test in patients with RAS wild type. Those are some important factors to know. We have several anti-HER2 therapies in clinical development that have shown encouraging results for patients with this biomarker.

Transcript edited for clarity.

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