Importance of Molecular Testing in Lung Cancer

Transcript:Mark A. Socinski, MD: Hello, and thank you for joining this OncLive TV Peer Exchange, “Treating Adenocarcinoma of the Lung.” Much progress has been made over the last decade in defining molecular subgroups of patients with adenocarcinoma of the lung. Many more studies are currently underway to further our understanding of how to use targeted therapies to personalize our treatment approach in these patients. In addition to targeted therapies, we also have several monoclonal antibodies at our disposal, including the recent addition of immune checkpoint inhibitors. In this OncLive Peer exchange, my colleagues and I will discuss how and when to use the therapies we have available and what to consider when choosing a treatment strategy for an individual patient.

My name is Dr. Mark Socinski, and I am a professor of medicine and thoracic surgery and director of the Lung Cancer Section at the University of Pittsburgh. Participating today on our distinguished panel are Dr. Benjamin Levy, an assistant professor of medicine at the Icahn School of Medicine and medical director of the Thoracic Oncology Program at Mount Sinai Health Systems; Dr. John Longshore, director of molecular pathology for the Carolinas Pathology Group; Dr. Gregory Riely, an assistant physician at Memorial Sloan Kettering Cancer Center and associate professor at Weill Cornell Medical College in New York; Dr. Thomas Stinchcombe, associate professor for the Thoracic Oncology Program at the UNC Lineberger Comprehensive Cancer Center at University of North Carolina, Chapel Hill; and his colleague, Dr. Jared Weiss, an assistant professor of medicine for the Division of Hematology and Oncology at UNC, Chapel Hill, Lineberger Comprehensive Cancer Center. Thank you again for joining us. Let’s begin.

I’m going to start with Ben. The title of our discussion today is “Adenocarcinoma of the Lung,” and we know that there are different subsets of non—small cell, adenocarcinoma being the most dominant one; squamous number 2. But the adenocarcinoma population is somewhat different. Can you just kind of give us an overview of that population from your perspective?

Benjamin P. Levy, MD: Sure. With lung adenocarcinoma patients, there are some important clinical characteristics to point out. Like squamous cell, unfortunately, 60% of patients do present with advanced stage disease. That’s speaking volumes of the need to define, declare these patients earlier through CT screening methods. Importantly, 20% of lung adenocarcinoma patients are never-smokers, which is a little different than the squamous cell population. And then if you look at patients who are either never- or former smokers, that percentage goes up to 60%.

So this is not necessarily a currently-smoking disease. Most of our patients, in fact, are either former smokers or never-smokers. And then, finally and most importantly, we had a firmer understanding of the genetic landscape of lung adenocarcinoma. We are now being able to molecularly characterize this disease better, and the list of driver mutations that we have that may predict sensitivity to targeted therapies is growing. It’s a very exciting time for us to be treating this patient population.

Mark A. Socinski, MD: Yeah, and that really was a paradigm that started almost 10 years ago with the initial description of EGFR mutations. I want to ask Dr. Riely to walk us through this population. What should we be thinking of? What should we be testing for? How should physicians begin thinking about tissue acquisition strategies to make sure we have enough tissue? And then we’ll also ask John after that to make some comments on making sure we have a good histologic diagnosis in the issues of tissue stewardship. So what should we test for?

Gregory J. Riely, MD, PhD: First of all, we need to think about when we’re diagnosing lung cancer, you need an accurate diagnosis. And in 2016, an accurate diagnosis means you understand the histology well and you have molecular testing done for that tumor, because all these things drive what patients are going to get in terms of treatment. So we need to know this up front. When we’re going to get tissue for that patient, we’ve known for 10-plus years that going for a fine needle aspirate, a simple one-pass needle biopsy, is not enough in 2016. We’re not going to get what we need in order to really answer all the questions we need. So, we need a big biopsy, whether that’s multiple passes with a fine needle, multiple passes with a core needle, or even surgical biopsies. Those are the ways that we go.

When we go to test, after we’ve passed through the histology and we’re testing for molecular testing, I’ve decided there’s two levels. There’s one that absolutely everybody needs to do every day, and then there’s the kind of thing that many of us do to learn more to qualify patients for trials. The absolute bare minimum for patients is we need to know EGFR mutation status and we need to know ALK status. I might extend level one to include ROS1 rearrangements because there’s an FDA-approved drug with clear activity in that area. So ALK, ROS, and EGFR are really critical for all of our patients with lung adenocarcinoma. And I’ll extend the lung adenocarcinoma group to patients who have small biopsies for squamous cell, as well. We don’t always know that that’s a pure squamous tumor from a small biopsy, and we need to include those patients in a lot of our molecular testing.

When I go past the first level that everybody should be doing, then I get into things that are a bit broader and can take more time. So I’ll say the first level should be done in clinic in 7 to 10 days. We should have those results to treat patients.

Mark A. Socinski, MD: And can I just make a point that for those three things we now have, at least for the first two, EGFR and ALK, we’ll get to this later, we have FDA-approved therapies that are better than chemotherapy. That’s the reason, too.

Gregory J. Riely, MD, PhD: Absolutely. That’s right. Randomized clinical trial data said platinum-based chemotherapy is inferior to targeted therapy for those patients, so we need to know that up front. When we get to the second level of molecular testing, there’s a broad spectrum of things. A lot of people take different approaches defining these, but there are things like BRAF mutations, MET exon 14—skipping mutations, a whole range of things that we’re really just beginning to understand and are really going to be important over the next few years. But today, I can’t expect everybody to have a platform for that.

Transcript Edited for Clarity