What is the Role of Biomarker Testing in Biliary Tract Cancers?

Transcript:

Laura W. Goff, MD: I’ll kick some questions back to you, Milind. Talk to us about biomarker testing in patients with biliary tract cancers. Do you test all patients? When do you test?

Milind Javle, MD: This is an evolving field. It’s been frustrating for you and me and others in the field because we don’t do biomarker testing as much as we should. When the Cholangiocarcinoma Foundation did a survey, 50% or 60% routinely ordered biomarker testing. These were individuals who came for the conference, so they were aware. In our experience [at The University of Texas MD Anderson Cancer Center], we try to get biomarker testing for everybody. I have to be candid: we’re successful in 50% or 60% because sometimes there’s not adequate tissue. A patient may have traveled and already had a biopsy that was inadequate, and a second biopsy was not pursued because the patient had already received some treatments by the time they saw us. For many reasons, biomarker testing isn’t as universally adapted as it should. I want to make the point that the NCCN [National Comprehensive Cancer Network] Guidelines recommend biomarker testing for all patients with biliary tract cancer because of the large number of actionable mutations. This is a work in progress as we improve our platforms and the awareness among physicians and patients. Hopefully we’ll get to a point when we can test it almost universally.

Laura W. Goff, MD: You mentioned the platforms. Tell me a little about the types of testing methods you’re using.

Milind Javle, MD: For biomarker testing, you’re absolutely right: the platform matters. At our institution, for the longest time, we had a 50-gene standard platform. That platform didn’t test fusions routinely. That has changed over the last couple of years, and individuals from platforms that are commercially available have been ahead of the curve in many cases. I encourage oncologists to choose an appropriate platform that’s broad enough to check all the actionable mutations. Typically, a platform has 400 or 500 genes and also includes fusion genes—for instance, FGFR fusions. These are molecular abnormalities seen with a relatively higher frequency in biliary tract cancer compared with other cancer types. An appropriate platform in that setting is of great value. What do you tend to use, Laura? Is there a specific type or platform that you recommend?

Laura W. Goff, MD: We’ve been in agreement with you that the commercially available platforms serve the needs and have stayed current. Our institutional platform uses Tempus, and we like to have tumor tissue when available. But in biliary cancers, sometimes that’s not feasible. The amount of tissue may not exist at all, or the amount of tissue may be exhausted. I’ve had pretty good luck with their circulating platform for tumor DNA as well. We’re using that commercially available platform.

Milind Javle, MD: This dovetails into my next question. What biomarkers do you look for in biliary tract cancer? The second [question] is [about] liquid biopsy. Do you use it? When do you use it?

Laura W. Goff, MD: Some are critical in terms of determining what’s standard to know. You wouldn’t treat a breast cancer without knowing the ER [estrogen receptor] and PR [progesterone receptor] status. For biliary tract cancers, particularly for intrahepatic cholangiocarcinoma—but really for all—it’s critical to know the alterations in the tumor. The most prevalent are FGFR alterations, notably fusions, which respond better to the agents that we have. Some minor alterations may also respond, like IDH1 mutations.

Some of the rarer alterations in the tissue-agnostic indications for drugs have been seen in biliary tract cancers [as well]. Rarely we’ll see MSI [microsatellite instability]–high tumors, but they’re important to find. HER2 [human epidermal growth factor receptor 2] is a little more common, and [there is] some promising activity of a variety of HER2-targeting agents. BRAF is another 1 you need to check, and we’ve seen patients respond with these alterations. NTRK is 1 you don’t want to miss, but it’s super rare.

Those are the usual suspects, but—you’ve published extensively on this—there are a lot of alterations in very low frequencies. [There is] a long tail of the curve. Although these patients are rare, they can have good responses. It’s important to look broadly for other alterations that we may be able to treat.

Milind Javle, MD: And liquid biopsies. Do you recommend them routinely? How do you use that in your practice?

Laura W. Goff, MD: That’s a really good question. I’m in the evolving phase of using liquid biopsy, specifically for finding targetable alterations that it can have a role in biliary tract cancers. Finding what may be a driver alteration for a patient and matching it to a drug is important, and many times, this is the only way we can get at the tumor to do molecular testing. I haven’t gotten into using it for serial testing. It’s still a bit experimental to use serial testing to assess response to therapy. The initial data are quite encouraging, and we should continue to include serial liquid biopsies in our clinical trials, but I don’t yet do this in routine clinical practice. How about you?

Milind Javle, MD: I think you’re right. Patients often ask me, “Should we do another liquid biopsy after chemotherapy?” Most of the data suggest there’s no need. But if they do get targeted therapy and there’s a [clinical] trial where the presence of acquired mutations can lead to some other alternative therapy or alternative trial, then we try to do it. But these tests are expensive, and the yield isn’t universal. We do it mostly when there’s a choice or a trial that will be impacted.

Laura W. Goff, MD: Our approach is going to evolve over the next couple of years very significantly, so I’m looking forward to what my answer will be in 2 years. This field is fun to be a part of because everything changes so quickly.

Transcript edited for clarity.