Frontline Treatment Landscape Advancements for Non-Small Cell Lung Cancer

Featuring Sid Devarakonda, MD, Director, Thoracic Oncology Program, Swedish Cancer Institute

Welcome back to PopHealth Perspectives, a conversation with the Population Health Learning Network where we combine expert commentary and exclusive insight into key issues in population health management and more. 

Sid Devarakonda, MD: I go by Sid. My name is Sid Devarakonda. I'm a thoracic oncologist. I'm a medical oncologist. And I treat patients with just cancers. Lung cancer, mostly, mesothelioma malignant cancers. I currently oversee the thoracic oncology program at Swedish Cancer Institute in Seattle. 

Interviewer: All right. Wonderful. What current frontline treatment options are available for patients with NSCLC that are covered by most insurance policies?

Dr Devarakonda: Wow, that's a, that question usually requires a pretty exhaustive answer. So, you know, we have made a lot of progress in the last, you know, a couple of decades, 20-25 years, so to speak. Traditionally, non-small cell lung cancer, especially in patients with metastatic disease, was conventionally treated with chemotherapy. We have had, you know, and these chemotherapies did okay, they were not that great. Most patients, you know, did not make it to one year. And that was a sad reality of this disease. But then as a science involved, our understanding of the cancer evolved and drug development, you know, saw a lot of progress. Now we really treat non-small cell lung cancers. 

First of all, it's not enough to call non-small cell lung cancer, non-small lung cancer anymore. We, you know, the most common subtypes of non-small lung cancer we see are carcinomas, squamous cell carcinomas. These are the two most common types, and then there are other rare types like neuroendocrine carcinoma, sarcomatoid lung cancer, and so on. 

Now, the first thing that we have realized is that many of these cancers, especially adenocarcinomas, often have a driver alteration, which is a very specific genomic change. And we harness that information to come up with the treatment plan for patients in the front-line setting. A good example for that is EGFR mutations, which are far more common in non-smokers, but you can also see them in patients who have smoke cigarettes. And then you have gene rearrangements like ALK, ROS1, RET. So there's a host of these mutations or genetic changes, and then that list keeps increasing year after year. And the reason we, that that's the first piece of information you need when you often treat patients with non-small cell lung cancer, is because you have treatments called targeted therapies that are very effective in managing patients with this format or this type of lung cancer. 

And in patients that don't have targetable operations, we now use immunotherapy. You know, it's the front and center of managing lung cancer of almost all stages. But immunotherapy is the predominant driver, and often we use immunotherapy alone or sometimes in combination with chemotherapy based on a level of expression of a marker called PDL1. So, yeah, these are all approved front-line indications. And then we can, you know, each of these biomarkers, so to speak, these genetic alterations is in itself a whole topic. And, you know, the same about immunotherapy. And this is just what's approved currently. And on the investigational side, we still have a lot more biomarkers, several new drugs that are being investigated.  

Interviewer: What identifying coverage for NSCLC treatments do payers consider coverage for patients who require 1L therapy due to mutations such as EGFR? 

Dr Devarakonda: I mean, ideally, we want to put our patients on the best possible treatment, right? That's the goal, whether it's on clinical trial or off clinical trial. And that decision from a clinician perspective for me is, you know, is it data driven? The choice that I'm picking? And is it appropriate for my patient? Because sometimes it's not just enough to show a tumor that has beautifully shrunk on the scan, right? And patients obviously do well when the disease is responding. But many of these medications do come with their own unique share of toxicities. So on the clinical side, when you identify a treatment, whether it is for patients with or without EGFR mutations in a very general sense, you're trying to find treatments that are effective, that are rooted in data, good quality data, and where, you know, the toxicity is really not atrocious and you're able to, you know, it has a reasonable toxicity profile. That's kind of what you're looking at.

And most times for these kind of regiments that are well rooted in data, these are often supported by national guidelines too. And insurance companies, you know, are supposed to pay for them. Right? And we often we find coverage to pay for these treatments and those other treatments we put our patients on. Every now and then, you might have some pushback from insurance companies, especially with regiments that have been recently approved. But then, often many times in my experience, of course, it takes away a big chunk of your time. But still, if you're able to justify the path that you're choosing for your patients, then often you are quite successful in securing approval. And it definitely helps now that the guidelines such as NCCN are pretty frequently updated. And that definitely helps the cost in obtaining coverage for these treatments. 

Interviewer: All right. Wonderful. So statistics tell us that patients often receive a lung cancer diagnosis only after the disease has spread to different parts of the body. Do you have any insight into screening options covered by health plans to prevent a delayed diagnosis? 

Dr Devarakonda: Yeah, this is the unfortunate part of lung cancer. It's the number one cancer killer, both in men and women. And obviously, identifying the cancer early is a huge area of unmet need. And the challenge here is that when, you know, most people have a tiny tumor spot growing in their lung, it's often not associated with symptoms unless it's blocking a windpipe, causing pneumonia, it's feeding into a blood vessel that's making people spit up blood. Often it goes undetected.

Now, there are two components to this, right? The major number one preventable cost for lung cancer is cigarette smoking. So that makes it easy to focus your screening efforts on one population. You can take patients with certain exposure to cigarette smoking, you know, the most criteria enough measure what's called pack years. And if patients meet certain criteria, then they can get load of CT scans on an annual basis and there is some data to support that. But the uptake for these has still been quite low, and there are several barriers to that with insurance coverage or the potential for insurance coverage being only one such. 

But then there is a totally different dimension to this where we are all a little bit lost and I'm hoping that in the years to come, medical science will give us a better way of tackling this question, which is, you know, your cigarette smokers, it's a little bit easier to identify because they will report a risk factor. But what about patients who have never smoked a cigarette, right? Because never smoker lung cancer is a major health problem. We see quite a few patients annually, depending on which part of the country you live in in the United States. And this is common in certain ethnicities. It's more common amongst, for example, middle-aged women and those of Asian descent. And this is a big problem for patients in the eastern part of the world, too. 

So how do you identify those patients for screening, right? And with every screening, there is a number needed to treat to be able to pick up tumors and it also comes with certain screening-related harms. So I think in the absence of good quality data, it's very hard to propose screening interventions, especially for never-smokers or those who have a very light smoking history. But really, I think this is an area of unmet need. 

And maybe going forward, it just won't be imaging varieties that we rely on for screening. We will probably use somewhat of a hybrid approach where patients get scans and maybe they get blood tests that involves some kind of a biomarker like circulating tumor DNA that will allow us to find and treat these tumors early before they have metastasized. 

Interviewer: It really is such a tricky situation because how can you treat what you don't know is there? So what can providers do to make treatment options more accessible to patients who lack coverage? Do you have any advice from your experience dealing with that?

Dr Devarakonda: It's always a challenge when patients don't have insurance coverage and, you know, it's a very complicated health care system that we, that we have and it's a very complicated world that we live in where there are so many social and economic inequalities. But, you know, largely from a physician perspective, we reach out to drug companies often and then we try to secure financial assistance for some of these medications, given how expensive they are otherwise. And there are some income criteria that companies will consider before they allow us to, you know, give us access to the drug through compassionate use and many large hospital systems including ours are very good financial aid programs that will help patients secure coverage through Medicare, for example, or help them with medical costs, you know, that that's the barrier that they have. But I still think it's a large challenge, not just at an institutional level or in oncology, but across society. 

Interviewer: It really applies to a lot of other disease states, of course, too, outside of just NSCLC. So you've done a wonderful job covering all the bases here, but is there anything else that you wanted to touch on that you didn't get a chance to or any other kind of messages you'd want to leave with our audience? 

Dr Devarakonda: I mean, lung cancer is a major global problem. It still claims a lot of lives every year, and I was, like I was just alluding to, it’s the number one cause of cancer-related death. You know, I think a few take home messages is that our understanding of lung cancer has changed. Lung cancer is not just a smoking-related cancer anymore. Which often tends to, even if that's the case, there is no reason why there should be any stigma surrounding this disease. But in general, the biggest risk factor for getting lung cancer is having lungs. It could be any of us that get lung cancer. So I think the increased awareness would probably help with, you know, early detection of cancers where persistent symptoms don't go unnoticed for a long time just because patients don't fit a certain stereotype. I think that's one, you know, area that I would really like to emphasize.

Two, for patients who or, you know, for people who still smoke, there is never a good time. You just have to stop smoking today, right. Right now. Because smoking all said and done is the number one preventable cause of not just lung cancer but cellular level diseases. Right? There’s a systemic number of people that die from cardiovascular disease and smoking is a huge risk factor even in that space. 

And finally, you know, our understanding of the disease is changing at so many other levels too, right? We now have understanding that maybe there's a small percentage of lung cancers or a modest size of lung cancers that may have some kind of familial predisposition. So as our knowledge of cancers of genetic, I'm sorry, as our knowledge of germline alterations in lung cancer continues to evolve, then maybe there will be a role for genetic counseling. And that could lean pretty heavily on for some, you know, very select kind of screening strategies. 

And finally, I think the, you know, every passing month, I feel a little bit more optimistic because this is still a bad disease. You know, we still have the success stories that we have, you can count on one hand, while you still have a vast majority of patients that don't have outcomes that you like seeing. So it's still a huge area of unmet need, but the optimism does come from the fact that drug development is progressing at an exponential pace. We have many good drugs in the pipeline, and it's no easy task. Things won't change overnight, but I definitely think we're headed in the right direction.

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