Optimizing Systemic Therapy in Advanced Colorectal Cancer - Episode 2

Liquid- Vs Tissue-Based Testing in Colorectal Cancer

Transcript: John L. Marshall, MD: Any role for repeat testing? So, in breast cancer, the standard of care is to do a new biopsy for HER2. How about in colon cancer?

Tanios Bekaii-Saab, MD: At some point, it would probably make sense. Right now, I don’t think I would advocate. For one, HER2 is still technically experimental.

John L. Marshall, MD: Even for RAS?

Tanios Bekaii-Saab, MD: For the RAS, yes. For the RAS and the BRAF, it’s unlikely to change much through life, at least genotypically. Phenotypically, it may, but you’re not going to capture that with a repeat test. I think, ultimately, we’re going to move away from tissue-based testing to liquid-based testing. That will essentially give you a snapshot of the changing genetic profile of some of the tumors over time. That would probably be more beneficial than just a glimpse, with one biopsy of a single site at a given time.

John L. Marshall, MD: A lot of people are talking about liquid biopsies. Is anybody using them as their primary way of testing?

Cathy Eng, MD: Not right now.

Tara E. Seery, MD: No.

Daniel G. Haller, MD: No. But the first one was just approved in lung cancer for EGFR mutations. So, the foot is in the door.

Cathy Eng, MD: Right.

Daniel G. Haller, MD: And you’re right. But in the Intergroup study that Peter O'Dwyer’s running, the so-called “Bucket or Basket,” we’ll be talking about TAPUR and MATCH. It’s the same sort of study. Stan Hamilton, the consultant on that, is mandating repeat biopsies of people who are more than 12 months out from their original archived primary tumor.

John L. Marshall, MD: I’m involved in a national molecular profiling effort. The reason I ask about this is that we’re sending serial samples. The primary gets sent and the metastases get sent, and we’re seeing a clear change over time. Just this past week, we found a patient whose primary tumor had all four proteins present; they had metastasis. We resect it, we happened to profile it, and it was MSI-high. We’re crosschecking to make sure the labs are correct so that we’re sure. I used my adjuvant therapy based on MSS (microsatellite stable), and now with metastatic disease, we’re in an MSI setting. So, I wonder if we’re only starting to understand the fluidity of the molecular profile of cancer.

Tanios Bekaii-Saab, MD: I think that that goes back to the point of liquid- versus tissue-based. The problem with the tissue-based is that you’re not capturing the same population of cells every single time you’re taking a biopsy. We know that the concordance rate is about 80%, so there’s actually 20% that are between metastatic and primary; 20% is a decently large number. You could interpret this as differences between sites rather than a changing genome. That’s one of the challenges with tissue-based biopsy.

John L. Marshall, MD: Tara, do you think it’s at a point where we should recommend to our audience to send it again or do another tissue? Are we not quite there yet? Is this all just talk at the academic level?

Tara E. Seery, MD: I think it depends on the patients themselves. If they have been stable for a long time and all of a sudden the primary is stable and something new grows, I biopsy that if it’s safe to biopsy; that’s the caveat.

John L. Marshall, MD: I think that’s really good advice. Anybody else, thoughts? Sound good?

Cathy Eng, MD: I fully agree with that, I think it’s very reasonable. If something is out of the ordinary, you need to resample it and reevaluate it.

John L. Marshall, MD: What’s the biggest pain in the neck that we can share with our audience about getting tissue done?

Cathy Eng, MD: Cost.

Daniel G. Haller, MD: Getting it paid for.

Cathy Eng, MD: Insurance approval.

John L. Marshall, MD: Coverage. To me, it’s access, too. Sometimes the only biopsy we’ve got is a colonoscopic biopsy. That’s a little alligator clip-sized snip, and it’s gone, so you’ve got to find it, and it takes time to figure that out, right? You send off a block, and they don’t have enough.

Tara E. Seery, MD: Sometimes you have to ask for more and do it again.

John L. Marshall, MD: How do we advise our audience, Tanios? Give me what you tell a general oncologist who sees regular colon cancer patients. How do they handle molecular testing?

Tanios Bekaii-Saab, MD: I think you have to really go where the money is right now and make sure that you have enough, in terms of prior authorizations, to get the whole RAS testing. It’s important to have BRAF for multiple considerations; some of them are actually therapeutic. MSI is, again, very important. It may also link back to a family history; that would be important to figure out. With smaller families, it’s sometimes very difficult to get a good family history by itself. And then HER2 would be on the lower list of priorities. I think it’s important, but I wouldn’t sweat too much over it right now. I think RAS, MSI, and BRAF would be important to start with to go down that decision tree.

Cathy Eng, MD: I think it’s important to think about HER2/neu testing because we taught people about BRAF testing because no one used to test for it before. Now people are testing for it, now we have trials for it. We know it’s a poor prognostic indicator. The reason I bring that up is that we know we’re going to have a trial with Herceptin as an option for patients. It’s less than 10% of patients that are HER2/neu-positive, but I still think we need to educate people.

John L. Marshall, MD: I completely agree with what you’re all saying. But the biggest pushback I get on this is doing an even broader profile and getting a ROS mutation, or some other mutation for ALK or something. And in colon cancer, how do I get the drug? I have a patient in the hospital right now whose profile we got back, and she’s HER2-positive. They could afford a month’s worth of this therapy, but not much more than that. So, we need a mechanism to get access to these drugs and study whether or not there’s positive outcome. Is there such a thing, Dr. Haller?

Daniel G. Haller, MD: There are a number of large studies we’ll be talking about—the MATCH trial, the big Intergroup trial, the bucket trials, the basket trials, etc. You’re trying to get information about this so that you have the backup for being able to do that. I’m saying that you have found an actionable mutation and you need an available drug. Getting all three things together is difficult. The only one we really have any evidence for are drugs we’ve had for 12 years now—since 2004. For example, cetuximab, the EGFR inhibitors, and panitumumab. I think that’s the one people absolutely have to do; the others are a little bit in the future.

Transcript Edited for Clarity