Transcript:Benjamin Levy, MD: Hello, and thank you for joining us for this OncLive Peer Exchange. Until recently, little progress had been made in the area of squamous non-small cell lung cancer. Now, with the excitement of recent positive trials and new drugs approved, there are increasing options for patients and the hope of improved outcomes, particularly after failure of chemotherapy. In this OncLive Peer Exchange, we’ll be discussing the most recent advances in squamous NSCLC and how they relate to patient care.

My name is Dr. Benjamin Levy, and I’m an Assistant Professor at Icahn School of Medicine and Medical Director for the Thoracic Oncology Program for Mount Sinai Health Systems and Associate Director of the Cancer Clinical Trials Office at Mount Sinai Hospital. Today, I’m fortunately joined by: Dr. Edward Kim, Professor and Chair for the Department of Solid Tumor Oncology and Investigational Therapeutics at Levine Cancer Institute, Carolinas HealthCare System; and Dr. Paul Paik, a Medical Oncologist for the Thoracic Oncology Service, Division of Solid Tumor Oncology, Department of Medicine at Memorial Sloan-Kettering Cancer Center.

Thanks for participating in this discussion. Let’s begin. I think what we’d first like to take on is the mutational landscape of squamous NSCLCs, but before we do that, maybe we can take a step back and talk about some of the differences in squamous cell and non-squamous cell as it relates to immunohistochemistry, and, more importantly, perhaps, clinically. I’ll take on the immunohistochemistry differences. Squamous cell lung cancer is typically stained a little bit differently. They are Napsin A and TTF-1-negative and p63-positive and also p40 can be used as well. p40 tends to be a little more specific than p63. And I think that this discernment is important in several aspects, 1) is that defining whether this is non-squamous or squamous helps with chemotherapy selection, and 2) is that in order to understand whether we need to do genetic interrogation for EGFR and ALK, this pathological discernment needs to happen. We routinely don’t test EGFR and ALK for pure squamous tumors, although I think there may be clinical scenarios where that’s the case. So I think that having a firm immunohistochemical diagnosis to discern squamous cell from non-squamous cell tumors is important.

Just as important, I think, are the clinical differences, the clinical presentation of a squamous cell patient, particularly an advanced squamous cell patient versus an advanced non-squamous patient, and perhaps differences in comorbidities. So, Ed, do you want to take this on and maybe talk to us about the differences in clinical presentation?

Edward S. Kim, MD, FACP: Thanks, Ben. It’s interesting and I’ve seen patients in Houston for over a decade and now I’ve been seeing patients in North Carolina, and there have been some differences in the population. One was a tertiary medical center, MD Anderson, and now we are at a very regionally-based community, sort of hybrid program where we do have doctors positioned in the communities at regional sites. It’s amazing to me. I saw hardly any squamous lung cancer when I was at MD Anderson, but we have a lot of patients who present with squamous cell cancer. It’s been astounding.

For the ones who end up in the hospital—and those are the ones who never make it to the large tertiary centers—we get a CT scan and we can’t tell right away if it’s small cell or squamous tumor because many times the presentation is of a central mass, one that’s very confluent with the mediastinum, causing some kind of bronchial constriction. The patients are dyspneic. We’ve already had several patients this year with either mild to moderate and one very severe superior vena cava syndrome with classical swelling in the upper extremities and the neck. I would say it’s a 50/50 coin flip whether it’s been squamous cell or small cell. And so that is what you see in more of a severe to moderate typical presentation of squamous NSCLC.

I think we get fooled every now and then when we see this peripheral lesion that’s a solid lesion and we biopsy it. We’re almost positive it’s adenocarcinoma. Maybe there’s a smoking history that confuses us, but typically what we’ve observed is patients who definitely have more comorbidities, they definitely are smokers, actively or recently quit, and they present with bulky disease that causes symptoms.

Benjamin Levy, MD: Do you feel that they’re more likely to have a marginal performance status? Is that something that you’re seeing in your clinic where these patients are more likely to be maybe an ECOG performance status 2 versus a 1? Does that make it harder to treat these patients?

Edward S. Kim, MD, FACP: Yeah. You know, we haven’t seen as many like that, honestly. It’s more of the severity of the disease that is impacting the performance status and their underlying comorbidities. But, had they presented a month earlier with maybe some hemoptysis or a cough, I would feel very comfortable treating them in the outpatient setting and I am amazed at the number of over age 70 patients we have seen, quite a few. I thought we would have a nice sort of gradient, 50s, 60s, 70s, and some 80s and I would say there’s a lot of 70 and 80 year-olds showing up with squamous cell cancer especially.

Benjamin Levy, MD: Paul, any thoughts, your experience with the squamous cell population? You see a lot of these at Memorial Sloan Kettering—difficult to treat, lots of comorbidities. What’s been your experience with your patient population?

Paul K. Paik, MD: Sure. So the overall experience matches Ed’s and I think the overall experience wherever you go in the United States is probably going to be similar—again, central disease. The main concern for these patients are the symptoms that they’re having and our need to really palliate these as soon as we can. I agree that the comorbidities are there. These are patients who are generally relatively heavy smokers so that goes hand in hand with existing lung disease and sometimes heart disease. And that’s a bit of a challenge, but really what we’re talking about is the cancer specific performance status that they’re hindered by.

I think apart from that, the outlier cases in terms of presentations that are atypical are also important to note because there are some of these cancers that do present, as Ed had mentioned, as peripheral tumors that really don’t have a lot of bulky central disease as you might expect. These can happen still in smokers. Some of these happen in lighter smokers, and I think this speaks to the fact that the histologic diagnosis remains important but also doesn’t tell the entire story.

Squamous lung cancers, in general, all look the same under the microscope just in terms of morphology. So, one of the things that we have to consider is the clinical characteristics for the patients and whether or not there might be also a different primary site as an origin. Head and neck is right up north of lung cancer, and so this is also a consideration in the differential diagnosis. So just keeping your eyes out for that in cases that present a little bit different from what you’re used to I think is an important consideration clinically.

Benjamin Levy, MD: I think that’s a great point. I had just one more question as it relates to these clinical phenotype or perhaps social history with these patients. Smoking. These patients generally are, for the most part, smoking or have been former smokers. For those patients who are smoking, are you instituting smoking cessation? I think we have data that patients who stop smoking or quit smoking do better in terms of their outcomes. Is this something you guys are encountering in your clinics or employing smoking cessation programs?

Edward S. Kim, MD, FACP: We do have a smoking cessation program. Like I said, we have a two-state regional touch point and I can tell you exactly where and in which counties there’s no way a smoking cessation program is going to work— in very working class folks who are doing their job every day and they don’t come in to the hospital to the emergency rooms. And so by the time they do end up making it there, they’re sick. So smoking cessation goes a little bit further down on the list upon their presentation, mostly because I don’t want it to interfere with the radiation we’re going to have to give them. Of course, these are not going to be patients who are qualified to take tyrosine kinase inhibitors. Yeah, we encourage it greatly and we try to hit them early but it’s been a struggle.

Paul K. Paik, MD: It’s the same thing with us. We have routine smoking cessation that we bring up at the initial visit. Particularly for the early stage patients in terms of maximizing future curability, making sure that we decrease the risk for any lung cancers. But it’s a challenge. These are patients in whom this has been a part of their life, by and large, and they’re faced, particularly with our patients, with metastatic disease. This is a new diagnosis for which, psychologically, smoking helps. And so it’s a great challenge but still something that’s very important to bring up routinely.

Benjamin Levy, MD: I agree with you. I’ve been surprised at how hard it is to get some of our patients to stop smoking. It’s been challenging. This is also a coping mechanism that patients rely on in a challenging diagnosis, so we’ve have challenges. But I would agree with Ed that we try very hard to get these patients to stop smoking.

Transcript Edited for Clarity