Lung Cancer Molecular Testing


Transcript:Benjamin P. Levy, MD: Hello, and thank you for joining us today for this OncLive Peer Exchange Panel Discussion on Metastatic Non-Small Cell Lung Cancer, a disease for which treatment decisions are determined by histology and, more importantly, molecular markers of the tumor. Advances in research continue to generate new drugs for this setting, adding to the complexity of optimally treating patients. Today I’m joined by a panel of world authorities in lung cancer medical oncology. Together, we will highlight the latest studies and will incorporate expert perspective on how the new data applies to decision making in clinical practice.

I’m Dr. Benjamin Levy, assistant professor of Icahn School of Medicine and medical director for the Thoracic Oncology Program at Mount Sinai Health Systems in New York. Joining me today are Dr. Chandra Belani, Miriam Beckner Distinguished Professor of Medicine at the Penn State Cancer Institute in Hershey, Pennsylvania; Dr. Marina Garassino, chief of the Thoracic Oncology Unit at the Medical Oncology Division of the National Cancer Institute of Milan, Italy; Dr. Sarah Goldberg, assistant professor of medicine at Yale Cancer Center in New Haven, Connecticut; Dr. Ramaswamy Govindan, professor of medicine, director of the Section of Medical Oncology, Division of Oncology at Washington University School of Medicine; and Dr. Mark Kris, professor of medicine at Weill Cornell Medicine and the William and Joy Ruane chair in thoracic oncology at Memorial Sloan-Kettering in New York. Thank you all for joining us. Let’s begin.

I think in this first section we’re going to be talking about molecular testing, state-of-the-art. And I think what we’ve witnessed in the past 10 years has been incredible advances in the development of targeted therapies. These developments of targeted therapies, of course, have been predicated on a firmer understanding of the genomic characterization of lung cancer. EGFR and ALK have been on our radar for quite some time, but there’s a growing list of rare yet actionable mutations underscoring the importance of comprehensive genomic profiling. Squamous cell cancers, while historically they have not shared the same advantages as adenocarcinoma, may have potential actionable mutations which may help drive therapy selection. And then finally, we’ll talk about plasma genotyping and the use of a minimally invasive blood test to reliably identify the genetic alterations within the disease within lung cancer.

So, given this list, Mark, given your leading role in the LCMC (Lung Cancer Mutation Consortium) and being on the cutting edge of a lot of this work, perhaps you can talk to us about what you’re testing for and how you’re testing.

Mark G. Kris, MD: Well, starting with the LCMC—and there are a number of LCMC sites here with me represented today—we had this concept that if you understood the genetic makeup of a certain tumor, you’d be able to better match treatments to the individual characteristics of that tumor. And, as you mentioned already, ALK and EGFR are sort of the poster children for that concept.

What’s happened over the last decade is that we found more drivers, and more drugs that target those drivers. In addition, there’s been a great development of technology to allow these drivers to be assayed, to have it done in a routine way, a cost-effective way, and a tissue-effective way; that is, frankly, available everywhere on Earth right now. And it’s very much like the CBC (complete blood count). I don’t even think it’s possible to order a white blood cell count. I don’t think it’s possible anywhere on Earth to do that. When you order the white blood cell count for all kinds of economies, you automatically get hemoglobin and automatically get a platelet count. It’s the same way with these DNA genetic-based tests. And so because we have these technologies, we not only can go after the ones you mentioned—the EGFR and ALK—but the others that have emerged. And the big ones that have emerged in recent years are ROS-1, RET, rearrangements in the RET gene, and, most recently, the identification of mutations in exon 14 of MET. The beauty about these things is these tests are not research tests. They’re all part of that same panel that’s already giving us the information on ALK and EGFR.

The second thing that’s happened here is that there’s been a revolution in the—I’ll call it the “Efficiency and Ease of Testing”—FISH tests, which used to have to be done for ALK, no longer need to be done, and next-generation sequencing, the current standard test. You can get very accurate measurements of amplifications in EGF and you can get an EGFR, too. But the ones we use mainly now are ALK, RET, and ROS. These targets I’ve talked about are particularly important because drugs exist today that can be used to target these new targets that we found. There was the approval of crizotinib a few months ago for those patients that have rearrangements in ROS-1. There’s the availability of cabozantinib recently approved now for renal cell cancer in addition to thyroid cancer and in MET.

As it turns out crizotinib was originally developed as an inhibitor of MET. It’s interesting if you go back to the phase I trial of crizotinib, which led to these discoveries. It says, “Trial of the new agent, an inhibitor of MET.” But it is a great inhibitor of MET. So, the beauty of these things is that it’s additional targets and it’s mutually exclusive, you find more targets at the same time, and you have a drug that can do that. And again, these drugs are already part of Compendia so any doctor can order it.

The one common denominator to this though, and really all the treatments for lung cancers, is adequate tissue. And I think what we really need to do is interact with our colleagues that give us the tissue specimens—interventional radiologists, pulmonologists, thoracic surgeons—and ask them to make sure that when they have lung cancer suspected, that enough tissue is there to do two things: to get a very accurate histologic diagnosis, and we’ll talk later I think today about why that’s so important, but also sufficient tissue.

Back in the day, it was just about getting enough tissue to make sure you can make the cancer diagnosis. That dynamic has changed now. And if you have that tissue, everything works quickly, and our pathology colleagues will also have the adequate tissue they need. There have been very dramatic time advances in therapy, advances in technology, but we still need to work on the human side to make sure we get the tissue we need in every patient and to make sure our colleagues understand why we’re asking for that. And I think it’s been everybody’s experience when the interventional radiologist knows why this is so important and they jump through hoops to get it done, and get it done right.

Transcript Edited for Clarity

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