Current Mutation Testing in Lung Cancer

Insights From: Roy S. Herbst, MD, PhD, Yale Cancer Center; Bruce E. Johnson, MD, Dana-Farber Cancer Institute; Mark A. Socinski, MD, Florida Hospital Cancer Institute


Roy S. Herbst, MD, PhD:
In 2016, we have recognized a large number of mutations that we test routinely in lung cancer—most of which are actionable, meaning that we can use a defined drug. When I see patients in my clinic with non–small cell lung cancer, I like every one of them to have an EGFR mutation test, a test for an ALK rearrangement, and a test for ROS1. Other tests are now routinely done for RET and BRAF. We do test KRAS, although that’s mostly for protocol. The actionable mutations would be, of course, EGFR, ALK, and ROS1—for which we have drugs and we use them.

Now, the data are beginning to emerge for BRAF. In a small percentage of patients with lung cancer, 3% to 4% of patients that have BRAF, usually a V600E, are usually treated with trametinib or, based on more data recently published, trametinib with dabrafenib. It’s exciting. Of course, the other thing that’s now come out is the test for PD-L1. Although it is a little bit different than the mutation testing, knowing a PD-L1 status is useful. We know that 25% of the patients will be high, and, in that group, they’re candidates for pembrolizumab, right now, in the frontline setting.

So, in my clinic at Yale, at the Smilow Cancer Hospital, we’re routinely, as a reflex, having patients get tested for EGFR, ALK, ROS1, and PD-L1. And then, as part of the testing that we do, we do a next-generation panel—we’re getting another 100 genes for the ride. We are getting KRAS and a whole host of other mutations. Those are still mostly for research purposes or for when we send the patients down to our early-phase drug development group, because there, there might be trials for specific genetic abnormalities.

Now, one thing that’s very exciting is the Lung-MAP trial, and I’m one of the leading investigators in that trial. Lung-MAP is a trial where we take patients with squamous lung cancer, put them through a Foundation Medicine panel, and look at 4 or 5 different marker groups. And then we have arms of that trial that match with those. For example, in squamous lung cancer, we know that the FGF (fibroblast growth factor) receptor is mutated or there are increased copy number variations in a small percentage of patients—10% to 20%. So, we’re finding those patients through a large international study in the United States and Canada—over 700 sites. Then, those patients get an FGF receptor inhibitor. We’re doing the same thing for CDK4/6 inhibitors—palbociclib being a drug that we’re studying for PI3-kinase. Testing is important, and testing will help patients. It will improve life and quality of life—some tests right now and others will, of course, as we learn more and we do experimental trials.

Bruce E. Johnson, MD: The typical genomic testing that we do for patients with nonsquamous non–small cell lung cancer is a next-generation sequencing panel. That typically involves several hundred genes where you characterize the mutations, as well as the chromosomal rearrangements and copy number assessment of the tumors. We think it’s important to do testing on patients at the time they develop metastatic disease. The times that we use the information for the standard treatment of patients with nonsquamous non–small cell lung cancer is at the time when they have disseminated disease. Therefore, we typically take the tumors and then do the testing.

Now, at my own center, and at a large number of academic centers, they do those large next-generation sequencing panels. As far as I’m concerned, the ones that are important to do in nearly any setting are those that would have an impact on the initial or subsequent therapy. At the current time, those include EGFR, or the epidermal growth factor receptor mutation testing; ALK and ROS rearrangement testing; and now, as it’s emerging, testing for mutations in the BRAF gene.

Mark A. Socinski, MD: At our institution, we routinely test all nonsquamous non–small cell patients for a number of actionable, or potentially actionable, mutations—one of which is BRAF. So, I think it’s important in the first-line setting, at the time of initial diagnosis, to have a very good understanding of the pathogenesis of the disease. And I think in 2016, that includes a number of potential mutations, or translocations, that we know we have targeted agents for that are quite effective.

Bruce E. Johnson, MD: The BRAF testing that we do at our institution includes not only the V600E mutations, for which there is currently drugs available, but also mutations that throw out the kinase domain of that gene. We have the luxury of doing a next-generation sequencing panel, so we get all that information. At the current time, it looks like there’s only going to be a drug for V600E mutants. So, out of the community setting, it’s likely that testing just for V600E will be adequate for the moment.

Transcript Edited for Clarity
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