The Latest Lung Cancer Research Updates From ASCO 2022

The Latest Lung Cancer Research Updates From ASCO 2022 from Patient Empowerment Network on Vimeo.

Dr. Tejas Patil from the University of Colorado Cancer Center shares the latest news in lung cancer research and treatment from the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting, including an update on immunotherapy.

Dr. Tejas Patil is an academic thoracic oncologist at the University of Colorado Cancer Center focused on targeted therapies and novel biomarkers in lung cancer. Learn more about Dr. Patil, here.

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Transcript:

Katherine:

Researchers came together earlier this summer at the annual ASCO meeting. Were there highlights from the meeting that lung cancer patients should know about? 

Dr. Patil:

Right. So, the ASCO ’22 meeting this year had some really interesting publications. So, for me, the key publications that I thought were kind of interesting from ASCO ’22, 2022, one was a publication looking at the role of immunotherapy in patients who are – have a very high PD-L1 expression, so greater than 50 percent. And there’s – 

Katherine:

Reminds us what PDL is. 

Dr. Patil:

Oh, yes, of course. So, PD-L1 is a biomarker. It’s a predictive biomarker that lets us know whether some patients will benefit from immunotherapy. It’s also prognostic because if patients have a high PD-L1 score, they tend to do better with immunotherapy than patients who have a low PD-L1 score. 

Katherine:

Okay.  

Dr. Patil:

Now the interesting data that was presented was a pooled analysis of all the immunotherapy trials to date. And there’s been this ongoing question in lung cancer as to whether patients should get chemo with immunotherapy or whether they should just get immune therapy alone.  

And this study showed that if you have a very high PD-L1 score, it is potentially possible to just use immune therapy and forgo chemotherapy. And I thought that was a very interesting analysis.  

There’s also several other papers that came out as well. Mostly there was a lot of interest in something called circulating tumor DNA. So, let me just take a step back. This is a type of molecule that can be detected in the blood that can help determine whether cancer is present in your blood or not. And there was a lot of publications at ASCO looking at using a concept called minimal residual disease.  

So, when we treat patients with early-stage lung cancer, a big question is how do we know they’re cured or not cured? And a lot of abstracts and publications this ASCO were looking at this concept of minimal residual disease. So, if I can detect some cancer in your blood after you’ve had cured curative therapies, we’re – we have a problem because there’s still cancer around and we’re detecting it in the blood.  

And I think this type of approach is going to really inform how we think about early-stage lung cancer management in the future. 

What Testing Should Take Place After Non-Small Cell Lung Cancer Treatment?

What Testing Should Take Place After Non-Small Cell Lung Cancer Treatment? from Patient Empowerment Network on Vimeo.

It’s well-known that patients should undergo testing before choosing lung cancer therapy, but what testing should take place following treatment? Lung cancer specialist Dr. Tejas Patil, from the University of Colorado Cancer Center, discusses the role of testing after treatment.

Dr. Tejas Patil is an academic thoracic oncologist at the University of Colorado Cancer Center focused on targeted therapies and novel biomarkers in lung cancer. Learn more about Dr. Patil, here.

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Transcript:

Katherine:

We know that patients should undergo testing before choosing therapy, but what testing should take place following treatment? 

Dr. Patil:

That’s a really good question. And it’s a complex question depending on the type of treatment that the patient is receiving. So, broadly speaking in lung cancer, we’ve separated the field into two types of treatments.  

Patients with lung cancers will get molecular testing at the onset, right? When they’re diagnosed to look for what’s called a driver oncogene. So, these are mutations that can be targeted with pill-based treatments. And if patients have these mutations, there’s about 10 of these right now and several in development, then the patients can receive a targeted therapy.

However, if they don’t have these mutations, then the standard of care right now is some kind of chemotherapy with immunotherapy. Now, the question asked was what kind of testing do you do after diagnosis? And that really depends on which camp you’re in. So, if you’re in the targeted therapy camp, my general practice has been to repeat molecular testing upon progression. The reason is that patients who are receiving targeted therapies typically evolved some kind of resistance to targeted therapy.  

Broadly speaking, you can categorize these as on target or off target resistance, but the major reason for doing repeat molecular testing is to understand a mechanism of resistance and then hopefully develop a new treatment with that knowledge. Now for the camp that doesn’t receive targeted therapies, let’s say they receive chemotherapy and immunotherapy, there it gets a little bit more nuanced.  

And if there is a role for repeating a biopsy and looking for dynamic changes in the patient’s cancer, but it is not routine and should be done with consultation with a thoracic oncologist. And really the idea here is that if patients who are on chemo immunotherapy progress, any additional molecular testing should really help inform what the next line of treatment will be and sometimes that can be a clinical trial.  

How Does Biomarker Testing Impact Non-Small Cell Lung Cancer Care?

How Does Biomarker Testing Impact Non-Small Cell Lung Cancer Care? from Patient Empowerment Network on Vimeo.

Biomarker testing identifies certain genes, proteins, or other molecules present in a biologic sample. Dr. Tejas Patil, of University of Colorado Cancer Center, discusses how results from these tests can be used to determine a treatment approach for non-small cell lung cancer (NSCLC).

Dr. Tejas Patil is an academic thoracic oncologist at the University of Colorado Cancer Center focused on targeted therapies and novel biomarkers in lung cancer. Learn more about Dr. Patil, here.

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Transcript:

Katherine:

Biomarker testing is important prior to choosing therapy for non-small cell lung cancer. What is this test and how long does it take to get results? 

Dr. Patil:

That is a great question. So, a biomarker is a biological molecule found in blood or other body fluids or tissues that is a sign of a normal or an abnormal process.  

Or let me reframe that as it represents having some kind of medical condition or disease. Now, it’s a very broad definition. Basically, a biomarker can be used to see how well the body responds to a treatment for a disease or a condition. And when we look at it from a genetic perspective, sometimes the term that you’ll see is a molecular marker or a signature molecule.  

So, these are terms that are sort of interchangeable with biomarkers. But the role of a biomarker is to help ascertain how well the body responds to a certain medical intervention, broadly speaking. 

Katherine:

Okay. What question should a patient ask their doctor about test results? 

Dr. Patil:

So that’s a very complicated question, and I will do my best to answer it succinctly. So, my personal view is that for any test to be meaningful, it should impact medical decision-making in some very concrete way.  

Specifically, with biomarkers, the result should either be prognostic or predictive and I’ll define what those terms are. So, a predictive biomarker is one that helps determine if a certain therapy will be effective. So, I’m going to use lung cancer as an example. In EGFR mutation in non-small cell lung cancer allows a doctor to prescribe an EGFR targeted therapy called osimertinib (Tagrisso). Therefore, in this example, the EGFR mutation is predictive.  

It opens the door for this targeted option that would otherwise not have been available if the patient did not have this EGFR mutation. A prognostic marker is a little different. This is the type of marker that helps categorize risk. So, in the same example I used earlier, that patient may have an EGFR mutation.  

They can also have a different mutation called TP53. Now this TP53 mutation doesn’t influence therapy. It’s not targetable, but it does influence risk.  

And so, there’s been a lot of emerging data to show that patients with TP53 mutations have worse outcomes on targeted therapies than patients without TP53. And in that case, that mutation is what we call a prognostic biomarker. 

How Does Immunotherapy Treat Lung Cancer?

How Does Immunotherapy Treat Lung Cancer? from Patient Empowerment Network on Vimeo.

How does immunotherapy work? Dr. Estelamari Rodriguez, a lung cancer specialist, explains how immunotherapy harnesses the immune system to kill cancer cells and how this treatment approach is transforming lung cancer care.

Dr. Estelamari Rodriguez is Associate Director of Community Outreach – Thoracic Oncology at the Sylvester Comprehensive Cancer Center, University of Miami Health System. Learn more about Dr. Rodriguez, here.

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Understanding Biomarker Testing for Non-Small Cell Lung Cancer Treatment


Transcript:

Katherine Banwell:

What is immunotherapy, and how does it work to treat lung cancer?  

Dr. Estelamari Rodriguez:

So, immunotherapy technically can be used to treat almost every cancer. So, it’s this concept that over time the cancer cells learn to bypass the immune surveillance, which is the way that your body identifies cells that are abnormal and gets rid of them.  

Your immune system can do that. And over time cancer grows and grows faster because your immune cells don’t even recognize that the cancer cells are there. So, immune therapy, specifically the checkpoint inhibitors, they target a receptor that is overexpressed in cancer cells, that make cancer cells invisible to the immune system. So, when you use, for example, some of these antibodies that bind the PD-L1, the programmed death ligand-1 receptor, that in itself gets rid of that veil that is covering the tumor cells. And now, your immune system can recognize the cancer. 

And that is one way of activating the immune system against the cancer, checkpoint inhibitors. There are newer drugs that are coming in the market, newer kind of engineered immune cells that will, in the future, be able to be developed for that specific cell. And in a way, immune therapy is more natural because you’re not getting a chemotherapy is that causes nausea or hair loss.  

You’re getting your immune system kind of ramped up, activated, against your cancer cells. It can have side effects of when you activate all these immune cells, you can cause inflammation in the body that has to be monitored, and some patients can be serious. And also, people have developed autoimmune kind of antibody reactions. So, there is a lot of monitoring that needs to be done. It’s given intravenously. We have doses now that last up to six weeks in some of the major immunotherapies that we use, like pembrolizumab, so you don’t have to come all the time. 

And I think the one thing that I’ve seen that is very promising about immunotherapy is that if you activate your immune system, almost like when you were young you got a vaccine, and you don’t have to get it every year, you have a memory response against that virus. Immunotherapy can achieve that for about 20 to 30 percent of patients today, where they get this memory against the cancer cells, and they could potentially come off treatment. 

Lung Cancer Targeted Therapy: What Is It and Who Is It Right For?

Lung Cancer Targeted Therapy: What Is It and Who Is It Right For? from Patient Empowerment Network on Vimeo.

How does targeted therapy work? Dr. Estelamari Rodriguez defines targeted therapy and shares how this personalized treatment approach attacks lung cancer cells.

Dr. Estelamari Rodriguez is Associate Director of Community Outreach – Thoracic Oncology at the Sylvester Comprehensive Cancer Center, University of Miami Health System. Learn more about Dr. Rodriguez, here.

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Transcript:

Katherine Banwell:

What is targeted therapy and who might it be right for? 

Dr. Estelamari Rodriguez:

So, targeted therapy kind of falls under the umbrella of precision medicine, where if you find a genetic driver, a mutation that is making that cancer grow. And out there we have drugs, we already have nine that are targeting specific genetic changes.  

The targeted therapy is really that treatment, either a pill, or an injection that goes after the genetic driver. And that, in a way, I describe to patients like you have a switch that went on and caused the cancer growth, and now with the targeted therapy we can put that switch off. And those treatments are very important because as they have evolved, they have kind of fill the gaps that chemotherapy had for patients. So, the one thing about targeted therapy is that because you’re going after one specific change, many times they’re less toxic. 

So, cytotoxic chemotherapy to kill lung cancer cells has to unfortunately kill a lot of good cancer cells in your body, specifically red cells, white cells, and platelets. So, that your body has to recover from all this normal tissue that dies, the normal cells that get impacted by the cytotoxic chemotherapy. In targeted therapy there is side effects, but a lot of them are decreased compared to chemo. 

And they’re really going after cells that have this mutation. So, preferentially you’re attacking the cancer and not the whole body. So, that’s an extra advantage for patients. And as we have patients live longer on these treatments, toxicity, and cause, all these things are really critical so that we develop better drugs that are even more specific targeting only what needs to be targeted and cause less side effects. 

Why Do Lung Cancer Patients Need Molecular Testing Before Choosing Treatment?

Why Do Lung Cancer Patients Need Molecular Testing Before Choosing Treatment? from Patient Empowerment Network on Vimeo.

How do a patient’s genetic mutations impact lung cancer treatment? Lung cancer specialist Dr. Estelamari Rodriguez emphasizes the importance of undergoing biomarker testing, also referred to as molecular testing, to identify genetic mutations, which may lead to a more personalized lung cancer therapy.

Dr. Estelamari Rodriguez is Associate Director of Community Outreach – Thoracic Oncology at the Sylvester Comprehensive Cancer Center, University of Miami Health System. Learn more about Dr. Rodriguez, here.

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Transcript:

Katherine Banwell:

What is molecular testing? 

Dr. Estelamari Rodriguez:

So, that is very critical for lung cancer patients today. So, molecular testing is when we get tumor cells, and we analyze the genetic changes that lead to that tumor growth. And that can be done today in different ways. The usual goal standard have been to do a biopsy of the tumor, and then do next generation sequencing when we analyze many, many genes that can impact cancer growth, and then we get a signature what drives that cancer. And in doing that, we discovered that some patients, for example, regardless of who they are, women or men, smokes or non-smokers, they may have a genetic driver that we have a treatment for, that does better than chemotherapy. 

So, that is important that you identify that as early as possible.  

Katherine Banwell:

Why is it necessary for patients to undergo molecular testing prior to a lung cancer treatment plan? 

Dr. Estelamari Rodriguez:

So, it is extremely critical because we have data today that several of these targeted treatments, the improvement of survival is not in the span of months, it’s in the span of years. 

People will do years better if they started with the treatment for their specific cancer driver mutation than if they received chemotherapy.  

We also saw that when immunotherapy came in the market a lot of patients, rightly so, doctors thought, “This is the best new thing, let’s put this patient on immunotherapy” and they were not testing patients for mutations before they started. And we found out two things, one is that there is toxicity if you give immunotherapy followed by some of the targeted therapies, specifically one called osimertinib (Tagrisso), so that you could cause harm.  

And then, number two, that immunotherapy doesn’t work in every case. A lot of patients with targeted driver mutations, they do better with a targeted treatment than they will do with chemotherapy and immunotherapy. So, I think it is important to define that early. We also now have approval for at least one targeted therapy after surgery. 

So, even patients that are early stage, which is not the majority of patients, but those patients also will get an improvement if they have an EGFR mutation specifically if they receive that targeted pill treatment after surgery. So, understanding the tumor is important so you can select the right treatment for the patient.  

Now, this is a dynamic thing, so tumors can evolve over time. So, there are many times that patients come to us for second opinions, and we actually recommend a repeat biopsy to understand the new genetic signature of that tumor because we may find a new option that was not there at the beginning. 

Which Tests Do You Need Before Choosing a Lung Cancer Treatment?

Which Tests Do You Need Before Choosing a Lung Cancer Treatment? from Patient Empowerment Network on Vimeo.

Why is it important to ask about biomarker testing for your lung cancer? Find out how test results could reveal more about your lung cancer and may help determine the most effective treatment approach for your individual disease.

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Transcript:

Why should you ask your doctor about biomarker testing?

Biomarker testing, sometimes referred to as molecular testing or genetic testing, identifies specific gene mutations, proteins, chromosomal abnormalities, and/or other molecular changes that are unique to YOU and YOUR lung cancer.

The analysis is performed by testing the tumor tissue or by testing tumor DNA extracted from blood to identify unique characteristics of the cancer itself.

So why do the test results matter?

The test results may predict how your lung cancer will behave and could indicate that one type of treatment may be more effective than another.

In some cases, biomarkers can indicate that a newer approach, such as targeted therapy or immunotherapy, may work better for you.

Common mutations associated with lung cancer include the EGFR, ALK, ROS1, BRAF, TP53 and KRAS genes, among others. In some cases, there are inhibitor therapies that target specific mutations. For example, if the EGFR mutation is detected, it may mean that an EGFR inhibitor, a type of targeted therapy, may work well for your type of lung cancer.

Another common biomarker associated with lung cancer is PD-L1. PD-L1 is a receptor expressed on the surface of tumor cells. The presence of PD-L1 indicates that a lung cancer patient may respond well to immunotherapy.

The results could also show that your cancer has a mutation or marker that may prevent a certain therapy from being effective, sparing you from getting a treatment that won’t work well for you.

Identification of biomarkers may also help you to find a clinical trial that may be appropriate for your particular cancer.

How can you insist on the best lung cancer care?

  • First, bring a friend or a loved one to your appointments to help you process and recall information.
  • Before you begin treatment, ensure you have had biomarker testing. Talk with your doctor about the results and how they may impact your care and treatment plan.
  • Finally, always speak up and ask questions. Remember, you have a voice in YOUR lung cancer care.

To learn more about lung cancer and to access tools for self-advocacy, visit powerfulpatients.org/lungcancer.

Lung Cancer and COVID-19 Vaccine Effectiveness

Lung Cancer and COVID-19 Vaccine Effectiveness from Patient Empowerment Network on Vimeo.

What do lung cancer patients need to know about COVID-19 vaccine effectiveness and safety? Expert Dr. Heather Wakelee shares information gathered about lung cancer patients early on in the pandemic and advice regarding COVID-19 vaccination.

Dr. Heather Wakelee is a thoracic medical oncologist and deputy director of the Stanford Cancer Institute where she also serves as the division chief of medical oncology. Learn more about Dr. Wakelee, here.

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Transcript:

Katherine:

I’d be remiss if I did not bring up COVID-19, and, I’m sure a lot of patients are curious whether the vaccine is safe and effective.

Dr. Wakelee:

So, we do believe the vaccine is safe and effective for patients living with lung cancer, and really important to be protected as much as possible. I was part of a group of other physicians around the world looking at the impact of COVID-19 on patients living with lung cancer. And, we collaborated with a group of physicians, Rayna Garcina was the lead. She was living in northern Italy at the time of the first wave, and so, was really face-to-face with it early on when there was so much we didn’t know. And, she gathered a group of us to watch and see, and what we were able to figure out before the vaccine was available was that people living with lung cancer who were overall healthy still except for their cancer were perhaps on a pill, targeted therapy, or immune therapy seemed to really not have that different of an impact compared to people who didn’t have lung cancer.

Chemotherapy was a little bit harder to see that but didn’t seem to be such a big issue. It’s different than people living with, say, leukemias or lymphomas where the treatments are impacting their immune systems even more. They seem to have worse outcomes. A lot of lung cancer patients were okay, but still, it’s a higher risk. And so, we want to protect our patients as much as possible.

So, we are, now that we have the vaccines, strongly advocating vaccines for any patient who was living with cancer really for almost anybody because as a physician, we really think that makes a big impact. We have not seen any negative impacts of the vaccine on any aspect of cancer treatment. It does not have a negative impact on how well the cancer is treated by the therapies. We did notice that when someone gets the vaccine, they can get some enlargement of the lymph nodes. That’s part of having an immune response is your lymph nodes get enlarged. And so, we did get a bunch of scans that the vaccines came out showing, “Well, this person has some lymph nodes in the axilla, which is the armpit.”

And it seemed to be correlating with the side that someone had a vaccine. And then, those go away. And, this was actually an interesting medical literature thing because for people getting screened with mammograms for breast cancer, there were suddenly all these lymph nodes showing up. But that was actually a sign that the person was responding to the vaccine, and it went away over time. And, it was a fine thing. It was just – I remember the first patient I had where that happened, we’re like, “Oh, well, that makes sense. Okay.” So, it’s okay. So, it was not cancer. It was just the immune response. But, yeah, so, we are recommending vaccines. There’s no data showing it is not working for lung cancer patients. The vaccines are less effective in people getting certain types of cancer treatment that are really suppressing the immune system. But even some response is better than none, and we’re still recommending the patients really do their best to stay safe with masks and things like that. 

What Are the Goals of Lung Cancer Treatment?

What Are the Goals of Lung Cancer Treatment? from Patient Empowerment Network on Vimeo.

The goals of lung cancer treatment can vary depending on the stage. Expert Dr. Heather Wakelee explains how lung cancer stage is determined and shares insight about the goals of treatment at each stage.

Dr. Heather Wakelee is a thoracic medical oncologist and deputy director of the Stanford Cancer Institute where she also serves as the division chief of medical oncology. Learn more about Dr. Wakelee, here.

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Transcript:

Katherine:

Let’s turn to treatment, Dr. Wakelee. On a basic level, what are the goals of treatment for lung cancer?

Dr. Wakelee:

So, with lung cancer, we’d love to cure everybody, that’s the ultimate goal, and do it in a way where people are able to continue living their life as they were before the cancer diagnosis. The ways that we do it, first of all, we’ve got to find the cancer, and that’s where screening is such an important aspect of things. If we can find the cancer at an earlier stage, we’re more likely to be able to cure someone.

So, what do I mean by “earlier stage?” Well, when a tumor first develops, usually, there is a single cell that develops a mutation, meaning a change in the gene, which gives that cell an advantage so it doesn’t die the way it’s supposed to. And then, it keeps growing, and dividing, and making new cells. And those over time get to a large enough size that they are the cancer. And given more time, those cancer cells start to spread into other parts of the body, usually first into what we call the lymph nodes, and from there then into other organs in the body. And this stage refers to health or how the cancer spread. So, the stage I cancer is still in that ball of cancer. Stage II means that it’s spread into some lymph nodes. Stage III is it spread into more lymph nodes, usually in the center part of the chest or mediastinum, and that’s where it starts to be much more difficult for the surgeons to be able to truly remove all of the cancer.

And then stage IV means that the cancer is not something that we’re going to be able to remove with surgery. It’s spread either within the lung to the lining of the lung or it has spread to other organs in the body. And so, when we talk about those stages that I, II, III, IV, it’s a bit more complicated than that. But, I think for most people, if they just think about it as stage I, just the cancer, stage II, lymph nodes and the lungs, stage III, lymph nodes in the center, and then stage IV, elsewhere, that’s a good way to kind of wrap your head around it.

And when we talk about stage I and II, that’s the truly early stage where we hope to be able to cure people with surgery. Surgery alone is enough for the majority of people with stage I cancer, and for maybe half, a little more than half of people with stage II. So, how can we be better than that? Well, that’s where there’s been a lot of new advances. So, adding chemotherapy after surgery can help a lot of stage II patients.

If the tumor genomic testing biomarkers shows that there’s a mutation called EGFR, we now know that there’s a pill drug that people can take that would prolong the time to when the cancer might come back. And then, just very recently, there was stated that that immune therapy drugs

IV can also prolong time to when the cancer comes back and maybe improve cure if the tumor has that biomarker called PD-L1. So, that’s that early stage. So it’s, again, getting more and more complicated and emphasizing that you’ve got to understand the biomarkers of the tumor to know how to best help someone.

When we move to stage III, some have surgery, but when you can’t have surgery, then we do the chemotherapy and the radiation. That’s the key part of the treatment there. And, we also know that immune therapy can be really helpful for a lot of patients when it’s given after the chemo and radiation’s completed. And then for stage IV, I talked about that already, which is you’ve gotta do the biomarkers to figure out the best treatments for some people starting with a targeted pill drug is the right thing if their tumor has those right gene mutations.

For other people, immune therapy alone might be an option if the PD-L1 level is very high and they don’t have one of those gene mutations in the tumor. And for a lot of people, chemotherapy or chemotherapy plus immunotherapy is the right strategy.

Katherine:

Would you help the audience understand the types of therapy for small cell lung cancer specifically?

Dr. Wakelee:

Yes. So, small cell still has the same kind of staging, but it’s a little bit more simple. We talk about extensive stage or limited stage. And what that has to do with is we rarely do surgery for small cell. It tends to have spread earlier. There are a few cases where that’s done, but normally, we divide it up into limited or extensive. And when we talk about that, limited is the radiation doctors can get all of the cancer in one radiation field, and then radiation plus chemotherapy is the standard approach to try to cure. If it’s more extensive than that, then it becomes extensive stage.

And, the best treatment are going to be chemotherapy plus those immune therapy drugs added together.

And so, the chemotherapy drugs that we use for non-small cell and small cell, the platinum drugs play a role in all of it. The drug we partner is a little bit different. There’s a drug etoposide we use a lot in small cell and a lot of other options for non-small cell. And then, the immune therapy drugs, there are a lot of options that are fairly similar for both small cell and for non-small cell. 

Which Tests Do You Need Following a Lung Cancer Diagnosis?

Which Tests Do You Need Following a Lung Cancer Diagnosis? from Patient Empowerment Network on Vimeo.

Which lung cancer tests do patients need after a diagnosis? Expert Dr. Heather Wakelee provides an overview of lung cancer testing, explains how the results are used, and discusses how testing differs for small cell lung cancer versus non-small cell lung cancer.

Dr. Heather Wakelee is a thoracic medical oncologist and deputy director of the Stanford Cancer Institute where she also serves as the division chief of medical oncology. Learn more about Dr. Wakelee, here.

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Transcript:

Katherine:

Can you provide an overview of important tests following a lung cancer diagnosis?

Dr. Wakelee:

That’s a fabulous question. When we think about the tests that we need to have done, they’re mostly tests that are done on the tumor, so, either if someone has a surgery or at the time of biopsy. and, that’s where we can figure out what we call, again, the histology that’s squamous or non-squamous. That’s when they look at it under the microscope. But, they also, with the tumor specimen, you can pull the DNA out of the tumor and then test for the gene mutations in the tumor. And, I always emphasize these are not changes in the genes that are in the whole person. They are things that are unique to the tumor. They are what make the tumor different from the rest of the person.

So, we look at those gene mutations, or that’s kind of a biomarker. So, there are a lot of terms that we use, and I know it gets really confusing. So, I try to use “biomarker” to mean all of these things, but that gene mutation is what we look at in the tumor tissue to see if there are specific changes that will allow us to give a pill therapy, a targeted pill therapy. And then, there are also aspects of the tumor that help us figure out whether or not the immune therapy might work, and most commonly, that’s something called PD-L1. That’s a protein that we look at on the surface of the tumor, and so again, under the microscope.

Katherine:

And, when you talk about extracting DNA, is that via a blood test?

Dr. Wakelee:

So, we have two different ways to do that. So, what I was talking about before was from the tumor tissue, you can extract the DNA. But now, there are these liquid biopsies where we can draw blood and find the tumor DNA that is different from the rest of the person’s DNA and look for those gene mutations in the tumor.

And that is where there’s a lot of developments happening. And, that’s so fabulous because they’re often faster results for patients, and it means that you cannot have to go through another biopsy. We still need the biopsy to establish whether or not there is even cancer. But, once we know that there’s cancer for sure, then we can use the liquid biopsies to get a faster information result on those gene mutations and to follow over time to see how the tumor evolves because tumors change after they’ve been treated.

Katherine:

Do you use imaging at all?

Dr. Wakelee:

Yes. Always. So, when someone is first diagnosed with cancer, we usually find that because of imaging, so, a CT scan or an X-ray, maybe they had a screening CT scan or maybe they had a cough that led someone to go get an X-ray, an examination. So, the imaging is a part of the original diagnosis. And in addition to CT scans, we’ll often get a PET scan that helps us look for, in a different way, the rest of the body, maybe an MRI of the brain to look in that area.

And then, wherever we’ve found the tumor, we will track that area with scans over time. And, it gets a little complicated for a patient that was found with what we call early-stage disease. So, stage I or II. Many of the times, those patients can have surgery and then we don’t have any tumor we can follow anymore. But we get CT scans to look to see if it could have come back. For patients with more advanced disease, so, stage III that couldn’t have surgery or stage IV, there we have areas that we’re going to continue to follow with the scans. And which scans and how often is going to depend a lot on what treatment the patient’s on and where the tumors are located that we’re tracking.

Katherine:

Do these tests differ for small cell lung cancer and non-small cell lung cancer patients? And, I know that non-small cell lung cancer is also known as NSCLC.

Dr. Wakelee:

Yes. So, long ago, the only distinction we had with lung cancer was that small cell versus non-small cell, and that is something that is seen under the microscope when that tissue is taken out from the biopsy. The pathology doctors look at it under the microscope, and the cells look different. And, the small cell lung cancer, those cells are small. It’s not very creative naming. And then, everything else is non-small cell or NSCLC. So, it’s SCLC and NSCLC. So, that was one of the first distinctions.

And, it is still very important because the chemotherapy drugs that we use are slightly different. And, the genetic, those gene mutations, we see them in any cancer. That’s what makes a cancer different from the rest of the body. But in small cell lung cancer, the tumor mutations that we see are not things that we know how to target specifically. In non-small cell, there are targets that we can target specifically for some patients.

So, just there, it’s different in having the targeted pill drugs in non-small cell, not so much in small cell. With immune therapy, those newer immune therapy IV drugs, they can work in both small cell and non-small cell.

But for small cell, the biomarkers, that PD-L1 level is not as important for helping us figure out who’s going to benefit. For non-small cell, with many of the drugs, it is important. So, there are differences there. 

What Are Biomarkers and How Do They Impact Lung Cancer Treatment Options?

What Are Biomarkers and How Do They Impact Lung Cancer Treatment Options? from Patient Empowerment Network on Vimeo.

What are lung cancer biomarkers, and how do they impact treatment options? Dr. Isabel Preeshagul defines biomarkers and explains how different biomarkers may help determine treatment options and aid in predicting treatment response. 

Dr. Isabel Preeshagul is a thoracic medical oncologist at Memorial Sloan Kettering Cancer Center. Learn more about Dr. Preeshagul here.

See More From INSIST! Lung Cancer

Related Resources:


Transcript:

Katherine Banwell:

Well, let’s define a few terms that are often confusing for patients. What are biomarkers?

Dr. Preeshagul:

Those are somatic alterations in the tumor just like EGFR, or ALK fusions, or MET exon 14, or MET amplification, or KRAS G12C.

These are all genes that are altered in the tumor. And these are genes that drive the tumor to grow. There are also other markers like PD-L1, which is a marker for response to immunotherapy. And there are various markers.

I could go on and talk about it for hours, but those are the more common ones that we know how to treat and how to handle and prognosticate.

Katherine Banwell:

And another term that’s sometimes confusing, what is a genetic mutation?

Dr. Preeshagul:

So, for genetic mutations, you have germline, and you have somatic. So, a germline mutation may be something like a BRCA1 or a BRCA2 that we see in patients with breast cancer or prostate cancer versus a somatic mutation which would be EGFR that I had mentioned or ALK fusion. So, germline mutations are the ones that we worry about being heritable.

And somatic mutations are those that are not thought to be heritable but thought to happen spontaneously within the tumor itself and cause the tumor to grow. We are constantly learning more about these though, however. But it’s really important to talk with your doctor to see if you have a germline mutation or a somatic mutation or if you have both.

And it is never wrong to seek an opinion with a genetic counselor to make sure that everyone in your family is safe, that you’re up to date on age-appropriate cancer screening, and that your family gets screened appropriately as well if indicated.

Katherine Banwell:

Are there specific biomarkers that affect lung cancer treatment choices?

Dr. Preeshagul:

Oh, definitely. One that I had mentioned is PD-L1. And this is a marker that we look for expression. So, based on FDA approval for pembrolizumab, if you have an expression of 50 percent or more, you are able to get immunotherapy alone in the upfront setting. If you have less than 50 percent, we often give you chemotherapy plus immunotherapy. And that’s based on a clinical trial known as KEYNOTE-189.

Other markers such as EGFR, as I had mentioned, ALK fusions, RET, NTRK, MET exon 14, ROS1, KRAS, HER2, you name it, those are alterations that we look for ideally in the upfront setting as well and can really affect treatment planning.

And those patients that harbor mutations like EGFR and ALK and ROS1 or MET exon 14, we know that these patients do better with targeted therapy upfront, not standard-of-care chemo. So, it’s really important to know about the presence of these alterations before you start treatment if possible.

What Key Tests Impact Lung Cancer Treatment Choices?

What Key Tests Impact Lung Cancer Treatment Choices? from Patient Empowerment Network on Vimeo.

Dr. Isabel Preeshagul, a lung cancer specialist, provides insight about lung cancer subtypes and how test results may play a role in determining the best treatment option for patients.

Dr. Isabel Preeshagul is a thoracic medical oncologist at Memorial Sloan Kettering Cancer Center. Learn more about Dr. Preeshagul here.

See More From INSIST! Lung Cancer

Related Resources:


Transcript:

Katherine Banwell:

When it comes to lung cancer, Dr. Preeshagul, what important tests should patients undergo that help in making treatment decisions?

Dr. Preeshagul:

So, it’s important to obviously confirm the diagnosis and make sure that it’s lung cancer, first of all. After that, you need to know the histologic subtypes. So, I mean, is this non-small cell, or is it small cell lung cancer?

And the difference between those two, it’s very important. They are not the same. Their treatments are different. Their prognosis is different. The staging is different. Everything is different. If you have non-small cell lung cancer, it’s important to know if you have adenocarcinoma or squamous cell carcinoma, large cell, neuroendocrine. It’s really important because the treatments vary. The prognosis varies. And how we approach those patients is different.

In addition to that, over the past 10 years, we have really come to understand the importance of next-generation sequencing testing, which I know we’re going to get to. But evaluating to see if your patient harbors any mutations or alterations that could be targetable because that would really change your treatment plan.

Katherine Banwell:

All right. So, let’s get to some of that testing. What is biomarker or molecular testing?

Dr. Preeshagul:

Sure. So, we use a lot of these terms synonymously. So, alteration, mutation, positive biomarkers, these are all basically one and the same. So, if you look at lung cancer 20 years ago, we really didn’t know about any of these. You had lung cancer, you got X, Y, and Z chemo. And that really was it.

But with the discovery of EGFR alterations and realizing that some patients harbor an EGFR mutation, and this mutation is what’s driving their tumor and then the discovery of erlotinib, or Tarceva, we realized that it’s important to evaluate for the presence of these mutations.

So, these are somatic mutations that occur within your tumor and drive your tumor to grow, and some of these alterations are targetable.

But some of these alterations that we find, unfortunately, and the majority of them, we don’t really know the significance of them as of yet, or we know the significance of them, but we don’t have a magic bean to treat them. But that does not mean that there won’t be something in the future.

How Genetic Testing Has Revolutionized Lung Cancer Treatment

How Genetic Testing Has Revolutionized Lung Cancer Treatment from Patient Empowerment Network on Vimeo.

Dr. Martin Edelman explains how genetic testing has revolutionized the lung cancer treatment landscape. Want to learn more? Download the Program Resource Guide here.

Dr. Martin J. Edelman is Chair of the Department of Hematology/Oncology and Deputy Director for Clinical Research at Fox Chase Cancer Center. More about this expert here.

View more from Fact or Fiction? Lung Cancer

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Transcript:

Patricia:

How is genetic testing changing the landscape?

Dr. Edelman:

So, genetic testing – and in this case the testing of the tumor, not the germline, not the individual – has been very, very crucial. If you go back about 20 years ago, there was a family of drugs called epidermal growth factor receptor inhibitors or EGFR inhibitors.

And the basic science at the time made it look like these would be best combined with chemotherapy in squamous cell carcinoma. And as it turned out, combined with chemotherapy they weren’t very useful. But as single agents, there were these occasional very dramatic results.

So, that came at a time when we were able to evaluate tumor DNA, sequence it with some degree of ease at a reasonable cost. So, there was a discovery of specific mutations, which were targeted by these drugs. So, it was sort of interesting in that it was the clinical observation that led to the discoveries in biology, not really the other way around.

But then that in turn resulted in looking for other mutations, which were found, and then the development of other drugs – in some cases, the repurposing of other drugs for those. And now we have about a half a dozen very validated targets, each one of which in a small slice of the population – between say 1 percent and 5 percent – 10 percent of the lung cancer population – but these – if the patient has within their cancer that particular mutation, these are drugs that are 80 percent-plus effective and frequently can be administered with relatively little toxicity.

And usually they’ll give them benefit for one-plus years or more. So, that’s been an example of progress there.

Could Advances in Lung Cancer Research Benefit You?

Could Advances in Lung Cancer Research Benefit You? from Patient Empowerment Network on Vimeo.

Expert Dr. Martin Edelman reviews the latest lung cancer research and explains how it may impact patient care. Want to learn more? Download the Program Resource Guide here.

Dr. Martin J. Edelman is Chair of the Department of Hematology/Oncology and Deputy Director for Clinical Research at Fox Chase Cancer Center. More about this expert here.

View more from Fact or Fiction? Lung Cancer


Related Programs:

 

How Genetic Testing Has Revolutionized Lung Cancer Treatment

 

Lung Cancer Treatment Decisions: Which Path is Best for You?

 

Could A Targeted Lung Cancer Treatment Be Right For You?


Transcript:

Patricia:

Let’s start with an overview of lung cancer’s research. Can you tell us a little bit about the field right now?

Dr. Edelman:

So, I think the field has been remarkable over the last few years. There’s been more progress, more drugs, more things that have happened in the last five years than probably the prior 50. It’s been an amazing time both for developments in microbiology as well as in immunotherapy of the disease, which is exciting for all concerned.

For patient’s, of course – really a promise of longer, better lives, even cures where we previously did not see any in advanced disease. For the scientists – an amazing amount of new information. And for clinicians and clinical investigators – just almost too many questions for us to answer.

Patricia:

It sounds like the field is really advancing quickly. What do you attribute that to?

Dr. Edelman:

Well, you know, I think there are a number of things. Everybody always talks about breakthroughs, but breakthroughs really happen after decades of other work. And what’s happening now is really a result of many, many years of different types of work. There were our colleagues in immunology who built this area of cancer immunology for many years – I have to say with much skepticism from many, myself included.

The advances in molecular biology – our abilities to do things with tumors to determine genetics at a rate and a pace and a cost that was previously unimaginable. All of these things have developed in the last few years but really are a result of the decades of work before that. If you look at immunotherapy – probably one of our biggest areas of progress – the roots of that are a century old. So, nothing’s really new. It’s just now we have the technology and the ability to really use it. And then I would also say that we’ve created the infrastructure that lets us test this – the people who have done the studies, the endpoints for the studies, the expertise in doing clinical trials – that also was there for decades, and we frequently were kind of ridiculed at times.

Oh, you’re just testing this drug against that drug, but the reality is is it was those incremental advances. It was the ability to know the endpoints, to refine the populations, to develop the infrastructure that allowed for all of this to happen.

Patricia:

Dr. Edelman, as a researcher in the field, tell us why you’re hopeful about lung cancer research.

Dr. Edelman:

Well, I think that we have gone from trials with very small incremental improvements and frequently a very slow degree of progress where if we had a positive study every two or three years, we were thrilled – to the point where we’ve had an avalanche of positive studies. I don’t think my younger colleagues know what a negative trial looks like anymore. Even our negative trials are pretty impressive. We’ve had studies where an immunotherapy agent was compared with chemotherapy. And it was designed to show that the drug would be better.

And it was just as good, and that was a negative study. That’s the correct interpretation, but still I would point out that that’s quite remarkable because these other drugs had taken us 25-30 years to develop. And now we have another drug with a very different mechanism of action that’s as good potentially. That’s impressive. I think we’ve just had an amazing degree of progress in the last few years. We have far more drugs. We understand far more about the disease – the technology at every point from diagnosis to assessment of response to the ability to evaluate better what we’re not doing well. So, our studies now frequently have biopsies before, during, and after treatment in a way of trying to figure out why is stuff working or not working.

Back in 2006 or so, I proposed a study. We ended up doing it, but it took two or three years because we were requiring a biopsy result – actually, not even a new biopsy but just an archived specimen from the original biopsy to determine eligibility, and there was strong pushback that we would never be able to do that. And now, we routinely are getting biopsies and re-biopsying, and that’s over a brief period of time.

So, we’re getting to get better understanding of the disease, and why stuff works and doesn’t work. And I think that that’s why our progress will accelerate. And I would again emphasize progress only happens – real progress – only through clinical trials. We’ve cured a lot of mice for many decades. A mouse is not a person. You actually have to do the studies patient by patient, and I think we are making substantial progress. We almost have too many things to test right now.

A Conversation With Dr. Jo-Anne Vergilio

A new year means new programs! We’d like to introduce to A Conversation With, which is a collection of conversations with healthcare leaders, including patient advocates and various healthcare professionals, to take a closer look at the topics and issues important to empowered patients, care givers, and their families.

In our first segment of A Conversation With, we spoke with Dr. Jo-Anne Vergilio the Senior Director in Pathology; Senior Associate Medical Director in Laboratory Operations, and Senior Hematopathologist at Foundation Medicine, Inc. Dr. Vergilio discusses what patients should know about biomarker testing and answers the following questions:

  1. How does biomarker testing work?
  2. How does biomarker testing help a cancer patient’s doctor with determining next steps in treatment?
  3. When in a patient’s course of treatment would they want to get biomarker testing?
  4. What is the difference between different kinds of biomarker tests?
    • Single marker vs. comprehensive
    • Tumor vs. liquid
  5. What does it mean for a biomarker test to be FDA-approved?
  6. If a doctor isn’t offering biomarker testing, what are some things that patients might say to their doctor?