Exploring Advantages of Molecular Testing in CRC Treatment

Dr Kristen Ciombor discusses utilization of biomarkers and molecular testing in the treatment of patients with CRC.

Kristen Ciombor, MD: In terms of molecular testing for colorectal cancer, in early stage disease, there are certain things that we look for no matter what, independent of stage. One is microsatellite instability [MSI] or mismatch repair deficiency. That’s important for a couple of reasons. No. 1, it can give us some information about the potential hereditary or genetic background of this cancer, which is obviously important for patients to know. It can also have an effect on prognostic and predictive therapy. We can tell how patients are going to do based on their MSI-high status. We can also sometimes develop treatments or target treatments accordingly. Other than that, most of our molecular testing is done in the advanced-stage setting, in stage IV. I’ll typically molecularly profile my patients’ tumors right away at diagnosis of metastatic disease because there are options that can immediately be affected by those results.

Molecular testing has advanced over the last few years. We used to think it was important only when patients had run out of good treatment options that were standard-of-care chemotherapy. Now we know that it can impact lines of therapy even in the first-line setting. That being said, there are some patients in whom their molecular profile can change over time. I’ll give you 1 example in a second.

It can be important to test at different lines of therapy. For instance, there’s a concept called anti-EGFR rechallenge, in which patients who have stage IV RAS or RAF wild-type colorectal cancer are often treated with anti-EGFR antibodies in their earlier lines of therapy. But in the face of that therapy, they can develop resistance to that drug. One mechanism of resistance can be the emergence of a RAS mutation or a clone. If you remove the anti-EGFR antibody from that patient’s therapy, then sometimes that clone will disappear. We can see this in liquid blood-based testing. We can monitor the emergence and decay of this clone, which can also lead to the potential for us to recycle that line of therapy once the mutated clone decays enough that patients can be resensitized to that. It’s important for us to be thinking about how to monitor molecular profiles over time. We’ll have more instances of that emerge as we learn more about the biology of these tumors.

Most oncologists and patients are starting to understand how molecular profiling can impact treatment. Patients ask me for particular molecular profiling platforms and other things like that. It’s great to see that word is getting out. Many patients—maybe not most—aren’t 100% aware of how molecular profiling can impact their treatment. That’s a conversation I have with many patients at the outset of their metastatic disease. I try to talk with patients about what these may mean. There are different platforms and ways to test that we can send. That’s important, but it can be overwhelming for patients. That takes a lot of time and usually happens over several visits.

From the oncology community at large, our testing and the uptake of our testing has improved over time. We see this reflected in the national guidelines, where it’s clear and has evolved over time regarding which genes and alterations are important to test for. We aren’t there yet. That’s certainly not ubiquitous for all patients. But another challenge we have is that we need this information quickly because many first-line therapies are based on the underlying genomic alterations. Not only getting it done but getting it done quickly and completely is of paramount importance.

Transcript edited for clarity.

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