Biomarker Testing in Metastatic Colorectal Cancer

Expert panelists provide their perspective on the current state of molecular testing in metastatic colorectal cancer and how it impacts treatment pathways.


John L. Marshall, MD: Hello and welcome to this OncLive® Peer Exchange titled, “Evolving Testing and Treatment Strategies in Metastatic Colorectal Cancer.” I’m Dr John Marshall, professor of medicine and oncology and chief of the division of hematology/oncology at Lombardi Comprehensive Cancer Center and Georgetown University [in Washington, DC]. I’m joined today by an amazing panel of experts in the field of colorectal cancer [CRC]. I’d like to welcome my esteemed fellow panelists to introduce themselves. Dr Eng, take it away.

Cathy Eng, MD, FACP: I’mDr Cathy Eng from Vanderbilt-Ingram Cancer Center, Nashville, Tennessee.

John L. Marshall, MD: Dr Tani Saab?

Tanios Bekaii-Saab, MD, FACP: Tani Bekaii-Saab, GI Medical Oncology at the Mayo Clinic in [Phoenix,] Arizona.

John L. Marshall, MD: Dr Parikh?

Aparna R. Parikh, MD: I’m Dr Aparna Parikh, from the Mass General Cancer Center, [Boston, Massachusetts].

John L. Marshall, MD: Last but not least, Dr Cohen.

Stacey Cohen, MD: Hi, I’m Stacey Cohen. I’m at the University of Washington and Fred Hutchinson Cancer Center in Seattle, [Washington].

John L. Marshall, MD: I want to welcome everyone here today from Chicago, Illinois, and I want to welcome all of you all who are listening in. Today we’re going to discuss a number of updates in diagnosis and treatment of metastatic colorectal cancer with a particular focus on the treatment of BRAF-mutant and HER2-positive disease. We will discuss the latest data in the context of CRC guidelines and their impact on clinical practice. Let’s get started.

I’m going to use the chair’s prerogative to set the stage for everybody out there. No need to tell you [all] what’s going on out there. We’ve made some more progress in the management of patients with both metastatic and earlier stage colorectal cancer. We’re going to dive into the adjuvant world and the role that ctDNA [circulating tumor DNA] MRD [minimal residual disease] testing might play in the management of these patients. We’ll start off with that kind of discussion, but we’re also going to talk about the role of precision medicine in the management of metastatic disease.

We don’t talk enough, in my opinion, about how we have been curing metastatic colon cancer, not so much the 5 of us, but our treatment colleagues in the surgery departments and interventional radiology and radiation. As we manage oligometastatic disease and the multidisciplinary team concept of that, we have new medicines, medicines that are very specific, [and] medicines that go for anybody at any time. We have even more evidence of VEGF [vascular endothelial growth factor] beyond progression, a new drug coming [soon]. That’s one more VEGF-inhibitor approval for that.

[We are] increasing immunotherapy options and increasing precision medicine options, so it’s a little more complicated than it was before. What I hope we accomplish in our session is to take apart a couple of main areas. [Dr Eng], we’re going to start with you. Talk about the biomarker testing really focused on metastatic disease.

Cathy Eng, MD, FACP: For any patient diagnosed with cancer, I think we all agree that microsatellite instability [MSI] testing is required on all of our solid tumor patients. Specifically in the metastatic setting, we want to test for RAS, and we want to test for BRAF. We want to also test for HER2, which is new. We have a new drug, tucatinib. And that is exciting. And we also know that there are various KRAS codons that we should be looking for [like the] G12C mutation; there are clinical trials for that. We want to try to enroll patients to those existing clinical trials. Molecular testing is of key importance for all of our patients.

John L. Marshall, MD: [Dr Bekaii-Saab], help us a little bit on when to do this. Is this something like in breast cancer, where you can’t even get started without knowing your molecular status? We all worry about turnaround time and getting going. What’s your strategy there?

Tanios Bekaii-Saab, MD, FACP: Understanding the challenges of the timing for testing, I think testing is essential, as [Dr Eng] mentioned. It is important to have some basic elements at least before you plan treatment. HER2, RAS, BRAF, MSI-high, at least, and then a number of others. Some of those are automatically done on tissues, such as MSI-high, and at our institution we’re doing HER2 IHC [immunohistochemistry] [testing] automatically now.

John L. Marshall, MD: Has everybody pretty much gone to that too? That’s a 48-hour turnaround time, isn’t it?

Tanios Bekaii-Saab, MD, FACP: Yes. It will give you that answer quick. But what we’re doing, and I’m sure others [are] as well, is it has become our standard practice to have every patient diagnosed with metastatic colorectal cancer to have a liquid biopsy and a tissue sent for a biopsy from HALO [Precision Diagnostics]. In fact, our nurse navigators have become trained to order those tests on our behalf even before I see the patient. So, by the time I see the patient, many times I have the liquid biopsy results, which take about 7 to 8 days.

There are limitations to that, at least for RAS and BRAF. There’s a high concordance between tissue and liquid. The problem is if you find it [in the] liquid, it’s in tissue. If you don’t find it in liquid, you still have to confirm its absence in tissue. That’s important as we increase our sensitivities of testing that remains somewhat of a limitation. But we’re in pretty good shape in terms of having adequate concordance to be able to, within a week, tell the patient this is the best option. Clinical trial support, as well. A lot of these clinical trials do require the presence of these targets early on.

John L. Marshall, MD: You’re getting 2 samples cooking, whereas a lot of doctors aren’t doing any samples. I was surprised to hear you say that you’re sending 2 assays out. I’m not. I’m sending mostly a tissue-based assay and waiting, but I get your argument around doing both. Also maybe downstream looking for resistance and [using] lung cancer mentality with the liquid. What are you guys doing about that?

Aparna R. Parikh, MD: I’m [doing] tissue and blood as well.

John L. Marshall, MD: You do both?

Aparna R. Parikh, MD: Yes.

John L. Marshall, MD: Right from the beginning you’re sending them. Two different companies usually?

Aparna R. Parikh, MD: It depends. It’s tricky because we have an in-house panel, so we do our tissue on in-house and then external commercial testing for blood.

John L. Marshall, MD: And so these are complementing each other?

Aparna R. Parikh, MD: They are, and I think we have moved to managing metastatic colorectal cancer in the noncurative setting as a chronic disease almost. So it helps me set my eye on the landscape of treatment. Even if the liquid may not impact my first-line therapy, it gives me a sense of where I’m headed with that patient. As we see more and more data about the ability to even rechallenge perhaps in the setting, it’s really helpful to know if there’s underlying resistance mechanisms that are in the blood that are subclonal that you’re not picking up on the tissue.

John L. Marshall, MD: I worry a lot about our testing and subclones. If we find one little clone that says it’s a RAS mutation, but the rest of the forest was RAS wild-type. Are we really representing things? So there’s a lot we don’t know, but we’re driven in that way based on these assays.

Transcript edited for clarity.

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