Updating Biomarker Testing Strategies as Cancer Care Evolves


Timothy J. Pluard, MD; Ossama Tawfik, MD; and Sujith R. Kalmadi, MD, reflect on how they update their biomarker testing strategies as the field of cancer care and precision medicine evolves.


Timothy J. Pluard, MD:Ossama, in terms of testing from tissue at the time of diagnosis of lung cancer, there other situations—I’m thinking particularly of breast cancer—where the biomarker profile might evolve over time, like with the acquisition of ESR1 mutations, which confirm resistance to endocrine therapy. Also, as we touched on briefly, the HER2 [human epidermal growth factor receptor 2] expression status is becoming a critical biomarker in breast cancer with the identification of the HER2-low subset of patients, and it may benefit from trastuzumab deruxtecan. How does that influence serial testing vs testing at frontline in liquid vs solid?

Ossama Tawfik, MD: That’s a loaded question.

Timothy J. Pluard, MD:It’s a lot.

Ossama Tawfik, MD: It’s a tremendous challenge. The first thing we start with, logically, is sitting together as a team. We create a game plan. What do we want to do? What do we want to know? That team should meet regularly. HER2-low is a perfect example. It came out last August, and our lives have changed. We have to be on top of things and work together to update that policy that we work with. You start by saying, do I have enough? If I don’t have enough, how do you expedite the information you’re going to get. I need to get on the phone and let you know that this isn’t going to be enough or whatever you want. Let’s do something instead of waiting so you can avoid the frustration that you get with the report with QNS [quantity not sufficient]. That’s critical for the success of the operation.

It’s all about communication and understanding the needs. That’s very important. Working in the lab, we have to inform our team that new studies are coming out, so please make sure you preserve the tissue when you’re starting to handle the specimen. Don’t consume tissue for additional testing that might be good for curiosity, confirmation, or diagnosis if you already have it. It’s going to be more relevant and more important to preserve the tissue to do the testing. As far as liquid biopsies go, they’re coming back full circle. We usually start with the next-generation sequencing [NGS], which everybody would like first. It’s frustrating because it takes a long time and is expensive. We might not have that. But tumor mutations and transformations are also important. I call those tumors live animals. They are so cunning and change their characteristics over the time. I see a tremendous value in liquid biopsies in treating patients after you get all the information about the patient the first time. They’ll definitely have a tremendous role.

Sujith R. Kalmadi, MD: Tim, can I interject for a quick thing?

Timothy J. Pluard, MD:Yes, absolutely.

Sujith R. Kalmadi, MD: There are 2 kinds of evolutions I’ve seen as a medical oncologist. One is obviously tumors evolve, and you can get mutations. With CLL [chronic lymphocytic leukemia], we’re seeing an evolution of chromosome 17 deletions and TP53. In breast cancer, we’re seeing HER2 overexpression. In lung cancer, I’ll treat it with EGFR drugs, and we’ve seen the MET pathway amplified. Those are all examples of how the tumors evolve over time.

The second thing that evolves, which we don’t pay as much attention to, is the evolution of knowledge. To give you an example, I had a patient with colon cancer about 7 years ago who was metastatic. I did a full genomic testing, which was considered standard of care at that time; this was 2015. Luckily, he had a good response to standard chemotherapy, EGFR-directed therapy, and such and made it 7 years. About 6 months ago, I had exhausted all my treatment options. He was still in good performance status, and I was debating whether to put him on a phase 1 clinical trial or on hospice [care]. Where do we go from here? For some reason, I said, “Let me order circulating tumor DNA.” I ordered that because I didn’t want to subject him to 1 more biopsy since he was getting weaker with all the chemotherapy I’d given him across the years.

The circulating tumor biopsy came back as an NTRK mutation. The patient doesn’t want NTRK treatment; he’s in full or partial remission. When I went back and looked at my NGS platform from 7 years ago, NTRK wasn’t part of the platform. There’s also the evolution of knowledge, which happens— not just evolution of tumor biology. We’ve got to be careful because some of these therapies are highly effective. When we see an NGS report in our chart, and you’re sitting there saying the patient doesn’t have any mutations, we’re thinking the patient doesn’t have mutations. In somebody like this, with a long natural history, it’s relevant to rethink and ask if we should we biopsy again because the platform has changed.

Timothy J. Pluard, MD:That’s a great illustration of the advances in the sequencing technology. We couldn’t pick up NTRK fusions on DNA because it’s an RNA seq identification, which wasn’t available routinely. On some of the platforms, it’s still not routinely available.

Transcript edited for clarity.

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