[MUSIC PLAYING] JOHN WHYTE: Welcome, everyone. I'm Dr. John Whyte, the Chief Medical Officer at WebMD. Let's talk cancer, specifically lung cancer. It's the leading cause of cancer deaths among men and women. 250,000 new cases a year, 130,000 deaths every year. 80% of lung cancer is something called nonsmall cell lung cancer.

So where are we today in terms of diagnosis, treatment, and what does the future hold? So to help answer these questions, I've asked two experts. Dr. Jyoti Patel, she's the Associate Vice Chair for Clinical Research in the Department of Medicine at Northwestern, and Dr. Benjamin Levy, he's an Associate Professor of Medicine at Johns Hopkins School of Medicine. Doctors, thanks for joining me.

JYOTI PATEL: Thank you for the--

BENJAMIN LEVY: Thank you.

JOHN WHYTE: Well, let's start off with, patients will often talk about lung cancer, but as I pointed out, there's different types of lung cancer. So for our audience, Dr. Patel, could you explain the different types of lung cancer?

JYOTI PATEL: Sure. Thanks very much. So lung cancer is much more heterogeneous than we ever thought. There are two predominant kinds. One is nonsmall cell lung cancer and that accounts for about 85% of all lung cancer. The other is small cell lung cancer, and that is decreasing in incidence, but is still a substantial amount of people, given the fact that lung cancer is so common.

We break down small cell lung cancer down into different types based on what the cancer cells look like under the microscope. So adenocarcinoma is the most common, well by squamous cell tumors, followed by large cell cancers. All of these distinctions have relevance in treatment opportunities for patients and treatment pathways for patients.

JOHN WHYTE: And then Dr. Levy, what are the risk factors for nonsmall cell lung cancer?

BENJAMIN LEVY: It's such a great question. I think we're still trying to learn about potential risk factors. Of course, smoking is one. That's the big one. We know that there's an intimate association with cigarette smoking and the development of nonsmall cell lung cancer.

Second hand smoke, patients that were exposed to secondhand smoke growing up with family members or close friends who were smoking that they were around, that's a risk factor. And then we get down into some of the others and we're still learning. Certainly radon is something that's in the soil and rock that can potentially lead to the development of lung cancer. There's been some nice studies looking at the link between radon exposure and lung cancer.

And they we're really, beyond that, trying to understand other potential causes. There's been some hints and clues from some studies that there may be environmental exposures and the worse the environmental pollution, the more likely you are to develop lung cancer. And I think we still don't know some of the risk factors for lung cancer, specifically for those patients who either never smoked and have never had second hand smoke exposure.

JOHN WHYTE: What percentage, roughly, are nonsmokers?

BENJAMIN LEVY: So this is data that we've come to learn all too well, that never smoking lung cancer is roughly 20% of all nonsmall cell lung cancer. That's a big chunk.

JOHN WHYTE: Sure, yeah.

BENJAMIN LEVY: As does never smoking. And then if we expand that and look at either never smokers or smokers who quit more than 10 years ago, that number goes to about 60%. So this is not a current smoking disease, although that's something that's out there. We need to destigmatize this in some ways to understand this.

JOHN WHYTE: Absolutely. Viewers should be aware that just because you're not a smoker doesn't mean that you can't get lung cancer. So Dr. Patel, how do patients present? Is it cough? Is it weight loss?

JYOTI PATEL: Most patients with nonsmall cell lung cancer present, unfortunately, with symptoms, and generally, that means that the cancer is more advanced. So symptoms can come from the primary tumor causing pulmonary symptoms like cough or shortness of breath. It can come off it's metastasized to another area. So pain in a joint, for example, bony pain. A lot of people will describe weight loss and fatigue that's preceded their diagnosis for some time.

Those are all significant changes. Clearly, someone is coughing more, coughing up blood should seek immediate medical attention. But often in retrospect, the symptoms are subtle. So sort of knowing your body and seeking medical attention.

We want to change this, though. We really want to get more people who have early stage disease when the cancer is curable and gives us the most opportunities for treatment. And so finding patients with early stage disease, which only represent about a quarter of all patients diagnosed with lung cancer, really means implementing screening programs for patients who are appropriate who have a history of smoking.

JOHN WHYTE: Well, let's talk about those screening guidelines, specifically as it relates to the number of years of smoking and age. It's not about chest X-ray. We stopped that a long time ago as a way to find, to screen lung cancer. Dr. Levy, what's the current recommendations for screening for nonsmall cell lung cancer?

BENJAMIN LEVY: Yeah, I think this has certainly moved in the past few years. We know that, based on a seminal work, The National Lung Cancer Screening Trial, NLST, that CT screens low dose helical CT scans in a high risk group, leads to decreased lung cancer mortality when compared to a chest X-ray. So we're talking about screening. We are talking about low dose helical CT scans annually.

The current guidelines are for patients who have a 20 pack a year history of smoking, or more, smoke now or have quit within the past 15 years, and are between the ages of 50 and 80. So that's a wide group of patients. I think that whether this increases and the guidelines get a little bit more flexible, we'll see. But clearly, we know that if we apply CT screening to this group, that lives can be saved and we can reduce lung cancer mortality.

JOHN WHYTE: So as I referenced, it's still the number one cause of cancer death, even as smoking rates have decreased. What are the current treatments available to patients?

BENJAMIN LEVY: Well, it really is divergent based on a host of factors. Obviously, we still have chemotherapy for patients and some of the chemotherapy that we offer to our nonsmall cell lung cancer patients is not the chemotherapy of the 1970s or '80s. These are newer drugs that are better tolerated. So certainly, chemotherapy is a potential option for some patients.

Clearly more exciting are some of the newer therapies or class of therapies. Immunotherapy, which I'm sure many patients have heard of, this is a class of drugs that turns the patient's own immune system against the cancer. And there's many ways to do that and many patients are eligible for this type of treatment.

And we may find out that while this immunotherapy works well in a stage four setting, it may be able to be leveraged in earlier stages of disease. And then finally, I would say targeted therapy, which I always have to have this distinction when I talk to patients. There's immunotherapy that harnesses the patient's own immune system against the cancer and then there's targeted therapy, which essentially is trying to go after the genetic underpinnings of the tumor.

So every patient should have what we call comprehensive genomic profiling, or molecular testing, or genetic testing done on the tumor, so that if we identify the right gene, we can give the right drug. And one last thing I'll say is, these are not genes you're born with. These are only genes in the lung cancer, and we now have novel technologies both on biopsy specimens and by a blood test where we can determine the genetic underpinnings of a tumor and, based on that result, can offer potential targeted therapies that usually come in the form of pills.

JOHN WHYTE: And Dr. Patel, where are we, then, in terms of five year survival? Thought I might have even heard you say the word cure.

JYOTI PATEL: So absolutely. We've made significant impacts in survival. So whereas 20 years ago, a patient diagnosed with nonsmall cell lung cancer was given chemotherapy, chemotherapy was limited because of toxicity and a response rate that might be 30%, a reasonable survival estimate was less than a year for most patients.

And now, 20 years later, with integration of immunotherapies and targeted therapies, we're seeing survivals that are multiple years for some patients. And, in fact, there are patients that we know who have had immunotherapies despite bulky disease, despite prior treatments, who remain with no evidence of disease.

We're not sure what cure really looks like now. These therapies are new. The first immunotherapies were approved in 2015 for lung cancer, and so that's still a pretty short runway. But there are patients who are off of immunotherapies with no evidence of disease.

Patients with targeted therapies and genetic alterations often also have very good outcomes with a single treatment, perhaps a pill that they're taking a couple of times a day for three or four years. One piece that is important to remember is that lung cancer has had this tremendous evolution.

There have been multiple approvals of novel therapies in the past year, and so the science is constantly changing. So what we think a survival estimate is in 2021 is probably not going to be true for a subset of patients in 2024.

JOHN WHYTE: I was going to ask Dr. Levy that. Thanks for setting that up for me. What does it look like in terms of treatment five years from now?

BENJAMIN LEVY: I think the sky's the limit and I think a couple of things I think about in the next five years. The first is looking at newer classes of drugs that are coming down the pike now, some of these drugs called antibody drug conjugates, which may supplant chemotherapy.

These are more selectively-driven chemotherapies that really more like heat seeking missiles that will go directly to the tumor rather than kill all rapidly dividing cells. So these are known as ADCs or Antibody Drug Conjugates, and whether we can leverage these in combination with targeted therapies or immunotherapies, I think we're really beginning to have a significant uptick in trials and really beginning to understand the signals, the safety, and efficacy signals of these drugs.

I think potentially more importantly is that we're going to understand in the next five years how to leverage all of these great therapies that we have for stage four in earlier stage disease. I think that's where we're really heading. And this is the way drug development usually works. You start in the advanced stage setting, and then they work really well, and then you move it to earlier stage.

And while we can cure a certain amount of patience with stage four disease now with immunotherapy, and that's true, we have some data on that, leveraging these drugs in earlier stage to really shoot for cure is where I think we're going to be in the next five years, and that's really exciting.

And if we couple this with CT screens that can identify cancers earlier and then be able to leverage the science that we already know about in the stage four and put it in the earlier stage, I think the sky is really the limit. I'm really excited. It's a fascinating time to be in the field.

JOHN WHYTE: So Dr. Patel, what do you say to a viewer who's diagnosed with nonsmall cell lung cancer? What do they need to be doing?

JYOTI PATEL: For a patient who is diagnosed with lung cancer, I really urge them to become their best advocates, and to find out and to learn about the disease. The world is changing tremendously quickly, and so understanding the genetic profile of your disease so you can ask to your physician and really do some shared decision making about novel therapies or access to clinical trials, it's a huge piece of it.

Second is to really understand that the world is changing and it may be that we're using a particular treatment now, but that hopefully would be a bridge to another therapy that may be available in a year or two that may be more impactful.

JOHN WHYTE: What do they ask their doctor? Do they say, is there a clinical trial? Is there other treatment? How do they ask for that genetic profile, which is such an important point?

JYOTI PATEL: So I think the best outcomes come when we know we have the most data about the tumor and we can really personalize therapy recommendations. Often when a patient is diagnosed with lung cancer, they want to get moving with treatment right away. Sometimes getting the genetic information, understanding the mutational profile may take a couple of weeks and it is a time in which patients feel like they're in limbo and don't really have a path forward.

I would urge that, if patients are well and tolerating the symptoms from their cancer, to take a step back and understand that, probably, cancer's been there for some time. Getting the right information for the right therapies is absolutely important.

The other piece is, we have all of these new therapies because of clinical trials and a minority of our patients in the United States participate in clinical trials. All of the therapies we use now were experimental even four or five years ago. And so to always consider if there's a clinical trial option, could you be getting something that's more innovative that may benefit you or could you be helping our overall understanding of lung cancer may help the next person who is afflicted with this disease.

JOHN WHYTE: I want to thank you both again for sharing your insights about the need for screening, the effective therapies that we currently have, as well as what's on the horizon.

BENJAMIN LEVY: Thanks so much.

JYOTI PATEL: Thank you.

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