Expert Perspective | New and Emerging Progress in Lung Cancer Treatment

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Expert Perspective | New and Emerging Progress in Lung Cancer Treatment from Patient Empowerment Network on Vimeo.

What’s the latest in lung cancer research? Dr. Thomas Marron from the Tisch Cancer Institute at Mount Sinai Hospital discusses the advances in targeted therapy and immunotherapy and what this progress means for patients with lung cancer. 

Dr. Thomas Marron is Director of the Early Phase Trials Unit at the Tisch Cancer Institute at Mount Sinai Hospital. Dr. Marron is also Professor of Medicine and Professor of Immunology and Immunotherapy at the Icahn School of Medicine at Mount Sinai. Learn more about Dr. Marron.

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Transcript:

Katherine Banwell:

Dr. Marron, you’re a leading researcher in the field. What new and emerging progress in lung cancer care are you excited about? 

Dr. Thomas Marron:

So, there’s many extremely exciting, targeted therapies that’re in development. And so, as I mentioned, we do genetic sequencing, and we get three to 500 genes’ worth of data. But we only have drugs to target around 10 of those.  

So, hopefully in the coming years, in the next three to five years, we’ll have many more options based on somebody’s genetic profile of their tumor. I think that also, within the field of immunotherapy, which typically are given to patients who don’t have those targetable mutations. 

Immunotherapy is really, has revolutionized the treatment of lung cancer and with immunotherapy, we’re actually able to cure a subset of patients while in the past, we always said patients with metastatic disease had incurable disease, but it was treatable disease, just not curable.  

Now, we are curing a subset of patients. Unfortunately, we’re not curing the majority of patients. But the field of immunotherapy is evolving very quickly with new therapies targeting new parts of the immune system.  

So, similar with targeted therapies, it’s really an umbrella term. So, targeted therapy is an umbrella term for dozens of different drugs. Immunotherapy, similarly, is an umbrella term for dozens of different approaches to the immune system. So, dozens of different ways to turn on the immune system so that the immune system does its job and recognizes and kills cancer. Because your immune system is in your body to tell the difference between foreign things like COVID and normal things like your lung.  

And cancer is somewhere in between and there’s probably hundreds of different ways in which cancer finds an ability to hijack our immune system and then turn our immune system off. And so, I think with these emerging therapies that we’re developing now and will be further developed in the next five to 10 years, I think we’re going to see another revolution happen in the setting of immunotherapy.  

Katherine Banwell:

So, what do these advances mean for non-small cell lung cancer patients?  

Dr. Thomas Marron:

So, in non-small cell lung cancer, immunotherapy has really changed the way that we’re treating patients from 10 years ago when we were giving chemotherapy alone, or maybe 15 years ago. Ten or 15 years ago, when I saw a patient with metastatic disease, I would have to have a very frank conversation with them and tell them that the median survival was 10 months and that this was an incurable illness that would eventually take their life. Now, with the introduction of immunotherapy, patients are living more than twice as long on average. 

And there are a subset of patients, somewhere between 10 to 20  percent of people that go into remission and stay in remission. And so, that really has revolutionized the treatment. Obviously, we’re not done, because we still have to help the remainder of those patients and our goal is 100 percent cure. But the fact that we’re even using the C-word, cure in our cancer clinics is really amazing. 

Antibody Drug Conjugates for Lung Cancer | Advances in Research

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Antibody Drug Conjugates for Lung Cancer | Advances in Research from Patient Empowerment Network on Vimeo.

What are antibody drug conjugates, and how are these new agents changing lung cancer care? Lung cancer expert Dr. Thomas Marron defines antibody drug conjugates and explains how they work to treat lung cancer.

Dr. Thomas Marron is Director of the Early Phase Trials Unit at the Tisch Cancer Institute at Mount Sinai Hospital. Dr. Marron is also Professor of Medicine and Professor of Immunology and Immunotherapy at the Icahn School of Medicine at Mount Sinai. Learn more about Dr. Marron.

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 Expert Perspective | New and Emerging Progress in Lung Cancer Treatment

Expert Perspective | New and Emerging Progress in Lung Cancer Treatment

Transcript:

Katherine Banwell:

What are antibody drug conjugates, and how do they treat lung cancer?   

Dr. Thomas Marron:

So, antibodies are proteins that have been manufactured. They’re a synthetic version of something that happens in our own body And they’re very specific for a very unique protein. And so, there are certain cancer proteins, there’s proteins on the surface of cancer that really aren’t expressed anywhere else in your body. And so, what we can do is we can develop these antibodies that basically are a heat-seeking missile. So, you inject them like chemotherapy, through an IV. But they’re a heat-sinking missile, and they go throughout your body, and they stick themselves to the cancer.  

And hopefully, they don’t stick anywhere else. And basically, antibody drug conjugate means the drug is conjugated to the antibody, meaning you basically have glued chemotherapy onto that antibody.  

And so, what it allows us to do is, instead of giving chemotherapy through the IV like we normally would, where that chemotherapy goes everywhere in your body, and that’s the main reason that you have toxicity.  

It doesn’t just go to the cancer, it also goes to your bone marrow, to your hair, to your intestines, has side effects. Antibody drug conjugates, the goal of them is to really deliver the chemotherapy directly to the tumor and spare the rest of your body, the toxicity from the chemotherapy that’s glued onto the antibody.

It’s important to note that they still do have side effects. So, some of that chemotherapy, for lack of a better term falls off the antibody or it might leak out of the tumor after it kills the tumor cells. And so, there is still the potential for toxicity, very similar to the toxicities that we see with chemotherapy.   

But so far, the data is very encouraging, both in lung cancer and other cancer types that antibody drug conjugates might be a superior formulation of chemotherapy, so better able to treat lung cancer. And we have a few drugs that’re actually probably going to be FDA-approved in the second line setting for non-small cell lung cancer. So, that’s for patients who have received standard first-line therapy and unfortunately, their cancer has progressed.   

And we actually already have one drug that was, it’s called Enhertu that was developed for breast cancer. And that’s now FDA-approved for lung cancer, for a rare subset of lung cancer patients who have an exon-20 HER2 mutation.  

And the patients I’ve treated with that drug do extremely well, and so I think it’s a very encouraging sign of what’s to come using more and more of these targeted chemotherapy regimens.  

Katherine Banwell:

Yeah. Well, that leads me to the next question, is there a patient type that ADCs are right for? 

Dr. Thomas Marron:

So, maybe is the question, answer. So, I don’t know because we don’t have good biomarkers right now to identify the patients that’re going to respond best to the drugs that’re in development, at least those ones that’re furthest along in development.  

And we’re always searching for biomarkers, which basically just means a test that we do on the patient’s biopsy or in their blood to tell us who’s going to respond to a therapy and who’s not. Unfortunately, right now we don’t have a good biomarker for these drugs.  

Hopefully as we do larger trials and we study biopsies and blood from the patients on those trials, we can identify the subset of patients that will do best with the therapy. Because we always want to make sure we’re getting patients the best therapy for them and we’re avoiding giving these therapies, because there are some toxicities to patients that aren’t going to respond to the therapy. So, it’s definitely a work in progress. 

How Has Lung Cancer Molecular Testing Evolved?

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How Has Lung Cancer Molecular Testing Evolved? from Patient Empowerment Network on Vimeo.

What are the latest advances in lung cancer testing? Dr. Thomas Marron discusses the role of molecular testing when choosing therapy and how innovations in technology have revolutionized lung cancer care.

Dr. Thomas Marron is Director of the Early Phase Trials Unit at the Tisch Cancer Institute at Mount Sinai Hospital. Dr. Marron is also Professor of Medicine and Professor of Immunology and Immunotherapy at the Icahn School of Medicine at Mount Sinai. Learn more about Dr. Marron.

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 Expert Perspective | New and Emerging Progress in Lung Cancer Treatment

Expert Perspective | New and Emerging Progress in Lung Cancer Treatment

Transcript:

Katherine Banwell:

What should patients understand about the results of molecular testing? 

Dr. Thomas Marron:

So, molecular testing is extremely important and anybody who has metastatic non-small cell lung cancer should get it. And increasingly, with the new drug approvals, even patients that have earlier stage disease, stage II and III disease should also get molecular testing. Molecular testing is important to identify if there is a potential therapeutic target.  

But it’s also important to know that it may predict a response to a therapy, whether that be a targeted therapy or something like immunotherapy. But there is no guarantee. So, there’s no specific result from a molecular test that tells you there’s 100 percent chance you’re going to be cured by Drug X.  

And so, it’s important to always know that we’re following the data and we’re giving patients the drugs that, based on the knowledge we have today is the best option for them, based on their molecular test. But it isn’t a guarantee. And sometimes these drugs will work transiently.  

And so, they may work for weeks, months, year but then they might stop working. And it’s also important to understand that the mutational profile may change over time, which is one of the reasons why we do these genetic tests. Oftentimes multiple times. Not just at the time of diagnosis, but also when patients’ cancer starts to grow so that we can see if there’s a new molecular target that we might be able to identify and treat with a novel therapy.  

Katherine Banwell:

Dr. Marron, are there innovations in technology that are aiding in the advancement of lung cancer research?  

Dr. Thomas Marron:

Yeah, so there’s lots of developments in the molecular tests that we’re doing. One of them is that we’re able to track circulating tumor DNA. So, as cancer is growing, it grows in this very unorganized aberrant way, because the on and off growth switches within the cancer, within the DNA are very dysregulated. And what happens is that often times, they’re releasing a lot of cancer cells as they’re growing or also dying and releasing their DNA into the blood.  

And so, through blood tests, we’re now able to identify the mutations in a patient’s cancer. And this is a real revolution in the initial diagnosis of metastatic lung cancer because in the past, we had to wait for three, four, five weeks in order to know whether a patient had a targetable mutation like an EGFR mutation. Or if we should use a more agnostic approach, immunotherapy or chemotherapy to treat the patient.  

But now when I see a patient, typically I see lung cancer patients on Fridays, I will take some of their blood, I send it off for the liquid biopsy analysis. And by that following Friday, so just one week later, I typically have an answer of if the patient has a mutation that I can target, let’s say with an oral medicine or if they’re a patient that I should be treating with immunotherapy. Additionally, circulating tumor DNA, increasingly we can use it to identify or track a patient’s progress, as far as response to therapy.  

And so, this has really been developed in other tumor types, but increasingly we’re using it in lung cancer where we can either track how much cancer they have in their body. So, very early on, we can see if the cancer is shrinking or growing. And additionally, we can use it to detect patients after surgery, whether or not they have residual disease in their body.

And so, a lot of the times patients will undergo surgery because let’s say on a CAT scan, you might only see one large, isolated tumor. But after we take that tumor out, now we can do a blood test to see if there might be microscopic bits of that cancer that were left over, that we weren’t able to see on a CAT scan or PET scan.  

And it’s that patient population that we think benefits most from either chemotherapy or targeted therapy after surgery. So, we’re using circulating tumor DNA, both in the metastatic setting, where cancer has already spread to other parts of the body. And also, in the perioperative setting, around the time of surgery or radiation where we’re trying to cure patients. And we’re now able to use this technology to hopefully increase the likelihood that we’re curing them. 

Advances in Targeted Lung Cancer Treatments | What You Should Know

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Advances in Targeted Lung Cancer Treatments | What You Should Know from Patient Empowerment Network on Vimeo.

Dr. Thomas Marron discusses how these therapies work to treat lung cancer, how the presence of certain mutations can impact care and treatment choices, and the research being done on new therapies to target specific lung cancer biomarkers.

Dr. Thomas Marron is Director of the Early Phase Trials Unit at the Tisch Cancer Institute at Mount Sinai Hospital. Dr. Marron is also Professor of Medicine and Professor of Immunology and Immunotherapy at the Icahn School of Medicine at Mount Sinai. Learn more about Dr. Marron.

See More from EVOLVE Lung Cancer

Related Resources:

How Has Lung Cancer Molecular Testing Evolved?

How Has Lung Cancer Molecular Testing Evolved?

 Antibody Drug Conjugates for Lung Cancer | Advances in Research

Antibody Drug Conjugates for Lung Cancer | Advances in Research

 Expert Perspective | New and Emerging Progress in Lung Cancer Treatment

Expert Perspective | New and Emerging Progress in Lung Cancer Treatment

Transcript:

Katherine Banwell:

Welcome, Dr. Marron. Would you introduce yourself, please? 

Dr. Thomas Marron:

Sure, I’m Tom Marron. I’m the Director of the Early Phase Trials Unit at the Tisch Cancer Institute at Mount Sinai Hospital. I’m a Professor of Medicine and also a Professor of Immunology and Immunotherapy at the Icahn School of Medicine at Mount Sinai. And I’m trained as both an oncologist and an immunologist.  

Katherine Banwell:

Excellent. Thanks for joining us today.  

Dr. Thomas Marron:

Thank you for having me.   

Katherine Banwell:

We know that the presence of certain mutations can affect lung cancer treatment options. Can you share the latest updates in targeted therapies?  

Dr. Thomas Marron:

Sure, so there’s been a lot of developments in targeted therapies as of late.  

Mutations in a patient’s cancer can represent a potential therapeutic target, and we have increasing numbers, every year we have new FDA approvals for typically pills that target very specific mutations and are able to either control cancer or even kill cancer. Additionally, we use DNA sequencing of tumors to identify mutations that could be predictive of a response to certain therapies. So, even though we don’t have a specific drug to target that mutation in their DNA, that change in their DNA that’s making the cancer grow, we do know that patients with certain DNA mutations do better on certain therapies than other therapies.  

And so, we can use mutations specifically to help guide therapy, even if we don’t have a targeted therapy for something like EGFR mutation or a KRAS mutation. And additionally, one of the things that we do as we’re treating patients is, often times we will give a patient with lung cancer a therapy and then their cancer may respond for weeks, months, even years.  

But then it might recur, or it might just start growing if it never went away entirely. And at that time, we’re oftentimes repeating the genetic sequencing, whether doing a biopsy or sometimes we can do what we call a liquid biopsy, which is just taking some blood and looking for some of the DNA from the cancer floating around in the blood.  

And the reason we do that is that if you see a change in the mutations, it might represent either a change in the type of cancer or it might represent what we call an escape mutation, or an escape mechanism where the cancer that had been responding to therapy X is now not responding because it changed its DNA to overcome the therapy you were given. And that might suggest that we try a specific new therapy, or that we just change our approach entirely.  

Katherine Banwell:

You’ve answered my next question to some degree, but I’m going to ask it anyway. How do these therapies work to treat lung cancer? 

Dr. Thomas Marron:

So, cancer is caused by changes in your DNA. So, your DNA is your instruction booklet on how cells should grow and when they should grow. And every cell in your body theoretically has the same DNA, except for, because of a variety of things like smoking or exposure to radon or just living in a large city full of pollution. As we get older, we basically accrue more and more mutations and changes in our DNA, our instruction booklet. And while most of these changes really don’t have any sequela, and they’re not going to affect the ability for the cancer, or for normal cells to grow.  

Sometimes you’ll get a mutation in a very specific gene that’s important for telling cells when to divide and when to grow and when not to grow. And you can think of it as a light switch where the light switch gets stuck in the on position and constantly, cells are growing and growing and growing and that’s when you have cancer. So, when you have these mutations, one of the approaches that we’ve been working on for the last few decades, in particular in the last few years.  

We have lots of these new drugs that target these mutations, and they basically turn that on signal off. So, they disrupt, it’s like turning the light switch off. You’re disrupting the constant grow, grow, grow signal and keeping the cancer from growing. Typically, we think of these targeted therapies that do this, not as cures for cancer, at least when patients have metastatic disease, but they’re very good at controlling cancer. And some of these therapies can work for years, even a decade and control the cancer. But often times, unfortunately cancer always finds a way to outsmart us, even when we’re outsmarting it.  

Katherine Banwell:

Right. Are there new mutations being discovered that can impact the future of small cell lung cancer care? 

Dr. Thomas Marron:

Well, I’m not sure I would say that there’s a lot of new mutations that’ve been discovered, per se. Every time that you come in and get a diagnosis of lung cancer, we typically will take the tissue and like I said, sometimes we’ll take some blood and do a liquid biopsy and look for a slew of different known mutations.   

And typically, we’ll look for anywhere from three to 500 known mutations in the cancer, even though we only have drugs to treat about 10 of those three to 500. The nice thing though is that as we learn more and more and more about these mutations and we study them, we are developing more and more drugs to address specific mutations. So, five years ago we really only had three different mutations that we could target.  

Now, we have around 10 because we have all these new drugs that target very specific mutations whether they be in genes like MET or RET or KRAS or BRAS.  

So, I think that while we aren’t necessarily discovering that many new genes, we’ve been looking at the genetic sequence of cancer and also, just the human genome for 20 to 30 years at this point, we’re discovering lots of new drugs that can target those specific mutations that we know patients have, but that most of the mutations we identify are not necessarily druggable targets.