Recommendations for Molecular Testing in mCRC

Transcript: John L. Marshall, MD: We continue to refine the way we treat advanced colon and rectal cancers, both in the perioperative and the metastatic settings. In this OncLive Peer Exchange® discussion titled “Therapeutic Strategies for Advanced Colon and Rectal Cancers,” I’m joined by an amazing panel of experts in GI [gastrointestinal] medical oncology. Today we are going to discuss the latest clinical data, including from the GI ASCO [American Society of Clinical Oncology] 2019 meeting, and how it pertains to your clinical practice. I’m Dr John Marshall, chief of the Division of Hematology/Oncology at MedStar Georgetown University Hospital, professor of medicine and oncology at Lombardi Comprehensive Cancer Center at Georgetown University, and the director of the Otto J. Ruesch Center for the Cure of GI Cancers in Washington, DC.

And participating today on our distinguished panel are not only very, very close friends but very, very smart people, starting with Dr Howard Hochster, distinguished professor of medicine, associate director for clinical research, and director of GI oncology at Rutgers Cancer Institute in New Brunswick, New Jersey. Howard, welcome.

Howard S. Hochster, MD, FACP: Thank you John, it’s a pleasure to be here.

John L. Marshall, MD: Glad you’re here. Dr Joleen Hubbard, associate professor of oncology and consultant for the Division of Medical Oncology at the Mayo Clinic in Rochester, Minnesota. Joleen, welcome.

Joleen M. Hubbard, MD: Thank you, John.

John L. Marshall, MD: Dr Chris Lieu, associate professor and director of the GI Medical Oncology Program at the University of Colorado School of Medicine in Denver, Colorado. Chris, welcome.

Christopher Lieu, MD: Thank you John.

John L. Marshall, MD: And last but, yeah, maybe least, Dr Tony [Bekaii-]Saab, professor of medicine and senior associate consultant, Division of Hematology/Oncology in the Department of Internal Medicine at the Mayo Clinic in Scottsdale, Arizona. Tony, good to see you.

Tanios S. Bekaii-Saab, MD: Good to see you, John. Thank you.

John L. Marshall, MD: So, thank you guys for joining and we’re going to jump right in and, Joleen, I’m going to pick on you first. So, you know we now have precision medicine in a lot of our diseases. Where are we today in colorectal cancer? What are you testing and when?

Joleen M. Hubbard, MD: For metastatic colorectal cancer patients, they get a bare minimum. Initially, when we start our clinical testing, it would be valuable to get molecular profiling’s, specifically microsatellite instability, any RAS mutations, BRAF mutations, and HER2-positive overexpression.

John L. Marshall, MD: Are you doing that right from the get-go as soon as you’ve got tissue?

Joleen M. Hubbard, MD: I’m doing it right from the get-go. And the reason why is, you know for the RAS and BRAF mutations, it is definitely going to influence what I use for first-line therapy, depending on sidedness. But also, I want to be prepared for what clinical trial I am going to enroll this patient in after first-line therapy. Specifically, we have a number of HER2-positive clinical trials going on, and I want to get the patient set up and ready to go.

John L. Marshall, MD: In a metastatic patient, you generally, a lot with our frontline mets [metastases] the only biopsy we’ve got is that colon biopsy, that little alligator clip biopsy. Do you think that’s good enough? Do I need to biopsy the met in the liver? What is your practice?

Joleen M. Hubbard, MD: I would say if your pathologist says they had enough tissue to do these available testings, the tissue from the colon is fine. But oftentimes, if there is not enough tissue, or if I am thinking about doing next-generation sequencing and I want to get some core biopsies, I will go ahead and biopsy a metastatic lesion as well.

John L. Marshall, MD: Yeah. Chris, let me kind of come back to you real quick. So, this concept of oligo panels versus a broad next-gen panel. We all work at really good institutions where we can get access to any of those things. What are you all doing? Are you going right for the big picture, or doing the oligo panel?

Christopher Lieu, MD: We do a little a bit of a hybrid of both. We do have an in-house panel that gives us a targeted sequencing of the genes that we’re most interested in. So as Joleen mentioned, we are interested obviously in RAS, RAF, MSI [microsatellite instability] status, HER2. We want to know this information so that we can choose the right frontline treatment for our patients. And then what we may do on the back end after we get that first targeted sequencing panel is to go to a much larger panel to look for a larger sequence of genes. The key here, I think, is really speed, right? So, if you can get an answer faster, you can initiate your treatment faster. If the panel takes a long time to get done, then you’re delaying treatment, and I think that causes a lot of anxiety not only for our patients but for our providers as well.

John L. Marshall, MD: You know the lung doctors, I can’t believe their discipline. When they see a new patient with metastatic disease they, even if that patient’s in the ICU [intensive care unit], they sort of wait for that molecular test to come back before initiating their frontline therapy. Are we so disciplined yet?

Christopher Lieu, MD: I don’t think so. But, of course, the lung oncologists also have the benefit of having many more targeted therapies to potentially offer their patients. Here, when you look at the frontline treatment for colorectal cancer, I think you’re always safe to start with FOLFOX/bevacizumab as a frontline treatment, if you know that your sequencing is going to take some time. But it’s always better to have that information upfront so you can create a treatment plan appropriately.

Howard S. Hochster, MD, FACP: I was going to say that the study, for example, for MSI does not even require a sequencing. That’s an immunohistochemistry test. That can be done on any biopsy. It’s really important to know before you start treatment. I mean other than that it’s not as big a difference as in lung cancer where if you have an EGFR mutation, you’re going to give them an oral drug instead of a bunch of chemotherapy. We don’t have that phase III data to tell us it’s better to do that, and that’s why I think we don’t have the discipline. But I do think that as studies come forward with anti—PD-1 for MSI-high patients, we need to have that discipline. And that doesn’t require a Foundation test. I mean you can just do IHC [immunohistochemistry] for HER2 and for MSI, and do your PCR [polymerase chain reaction] for your RAS and RAF, and that pretty much gives us…

John L. Marshall, MD: And you get that within a week or so for most places.

Tanios S. Bekaii-Saab, MD: Yeah, a couple of days.

John L. Marshall, MD: But the PCR takes a little longer than a couple of days.

Tanios S. Bekaii-Saab, MD: You know if they’re doing a PCR test, it shouldn’t take that long. It depends if they’re sending it out or not, and how long the vendor takes.

Transcript Edited for Clarity