Tag Archive for: rash

What Helps Determine a CLL Patient’s Treatment Options?

What Helps Determine a CLL Patient’s Treatment Options? from Patient Empowerment Network on Vimeo.

What guides a CLL treatment choice? Dr. Catherine Coombs discusses genetic mutations and factors that may help determine a CLL patient’s therapy .

Dr. Catherine Coombs is an Assistant Professor of Medicine in the Division of Hematology at The UNC Lineberger Comprehensive Cancer Center. Learn more about Dr. Coombs here.

See More from Thrive CLL

Related Resources:

 

Setting CLL Treatment Goals WITH Your Team

Signs It Is Time to Treat Your CLL

Signs It Is Time to Treat Your CLL

CLL Treatment Approaches: What Are the Types?

Transcript:

Katherine:

There’s not necessarily a one-size-fits-all approach to treating CLL, so how do you decide which treatment is right for a patient?  

Dr. Coombs:

I always look at their underlying disease biology. There’s a couple really important tests that I send for all of my CLL patients by the time that they need therapy. The first is to see what their underlying cytogenetics and molecular findings are. There are certain good findings, and then certain bad findings.  

One of the bad findings is having a deletion in the 17th chromosome in the short arm of that chromosome. The chromosomes are the big pieces of DNA within everyone’s cells. There are findings that are common in CLL: a 17p deletion is a poor prognostic feature. There’s a separate test where we can actually identify mutations in a gene called TP53. And these behave largely the same as 17p deletions, so I always check for both. It’s two different tests.  

Oftentimes patients have both of these findings: a 17p deletion and a TP53 mutation. But sometimes you can have the mutation without the deletion and vice versa. That is one finding that’s important when talking about different therapies. The other really important prognostic test is the IGHV gene mutation status. This is another specialized sequencing test. It looks to see if the patient’s heavy chain, if their immunoglobulin protein has undergone something called somatic hypermutation or not.  

It’s actually good to be mutated. What we know about people who are mutated is that they typically have better responses to most therapies and their disease typically is one that grows slower. So, I use those factors and then I have a conversation with the patient. The two main treatment classes that I spoke about – so the BTK inhibitors, those work actually really well and even the people with these bad prognostic features.  

So, people with the 17p deletion, people with the TP53 mutation, they can have disease control for six plus years on a BTK inhibitor, which is really good.  

That was not the case a decade ago when we didn’t have these drugs. That’s something that’s been hugely beneficial for our patients. The venetoclax/obinutuzumab regimen, that still works when people have the 17p or the TP53, but it probably doesn’t work as well.   

I’d mentioned the median time for disease to come back hadn’t been reached yet. It had been reached for that poor risk subset. The expectation for people with that poorest marker is that the median PFS, progression-free survival. So, again, when after someone starts therapy, when the disease then progresses is 49 months. It kind of gives me a rough estimate of, “Gosh, these are your therapy options and based on your underlying biologic factors unique to your disease, this is what you can expect out of therapy A or therapy B.”  

The mutated or unmutated IGHV, similarly, those BTK inhibitors work extremely well, even in people with the bad unmutated finding. I think those are always an option. The other treatment is an option, but the people with that bad finding do have a shorter time until they progress of just under five years.  

Signs It Is Time to Treat Your CLL

Signs It Is Time to Treat Your CLL from Patient Empowerment Network on Vimeo.

When is it time to treat your chronic lymphocytic leukemia (CLL)? Dr. Catherine Coombs reviews the criteria doctors consider when deciding whether it is time to begin therapy. 

Dr. Catherine Coombs is an Assistant Professor of Medicine in the Division of Hematology at The UNC Lineberger Comprehensive Cancer Center. Learn more about Dr. Coombs here.

See More from Thrive CLL

Related Resources:

What Helps Determine a CLL Patient’s Treatment Options?

Expert Advice for CLL Self-Advocacy

Refractory vs Relapsed CLL: What’s the Difference?

Transcript:

Katherine:

When is it time to treat? What factors do you look at? 

Dr. Coombs:

There’s pretty well-established guidelines for when treatment is indicated. The international workshop for CLL has these published guidelines, so it’s something you could Google. Off the top of my head, the main reasons that I do treatment, which are included in these guidelines, are one, if the patient has low blood counts due to the CLL, so that could be anemia or low platelets. Two, if they have bulky lymph nodes. They actually define bulky as 10 centimeters. So, that’s pretty big.  

Or, if the lymph nodes are being symptomatic in some way, they’re bothering the patient, they don’t have to be that big. Three, if the patient has bulky spleen enlargement or if it’s causing symptoms. The spleen is next to the stomach. So, say some patients may not be able to eat a full meal, that’s another reason we could do treatment.   

Another reason is if the CLL is causing constitutional symptoms. Sometimes these are black and white. One is unintentional weight loss of 10 percent or more of the body weight. The one that’s not always black and white is fatigue. Patients can have fatigue from the CLL, but I’ve found often fatigue can be due to other causes. So, that’s something I consider an important job of mine is to make sure we don’t jump into CLL treatment if say, there’s some other cause for the tiredness, such as, say the thyroid’s off, or there’s a huge amount of stress due to some other factor outside of the CLL.  

Then, some other constitutional symptoms are CLL can cause fever or drenching night sweats. Those two it’s important to make sure that there’s not a concurrent infection because infections can also cause those symptoms. The last indication is patients with CLL can develop autoimmune cytopenias. That’s when the immune system attacks some component of the blood cells. Most commonly that’s an autoimmune anemia or autoimmune thrombocytopenia. That’s the term for low platelets.  

Usually, we can treat that with steroids or occasionally CD-20 by itself like rituximab to calm down the immune system. However, if those immune-based therapies fail the patient, then we could consider treating the CLL to help fix that problem.  

Exciting Advances in Waldenström Macroglobulinemia (WM) Treatment

Exciting Advances in Waldenström Macroglobulinemia (WM) Treatment from Patient Empowerment Network on Vimeo.

What new therapies are on the horizon for patients with Waldenström macroglobulinemia (WM)? Dr. Shayna Sarosiek from Dana-Farber Cancer Institute reviews promising developments in WM treatment, including immunotherapy and BTK inhibitors.

 Dr. Shayna Sarosiek is a hematologist and oncologist at the Dana-Farber Cancer Institute where she cares for Waldenström macroglobulinemia (WM) patients at the Bing Center for Waldenstrom’s. Dr. Sarsosiek is also Assistant Professor of Medicine at Harvard Medical School. Learn more about Dr. Sarosiek, here.

See More From The Pro-Active Waldenström Macroglobulinemia Patient Toolkit

Related Programs:

Emerging Waldenström Macroglobulinemia Treatment Approaches

Emerging Waldenström Macroglobulinemia Treatment Approaches 

What Are the Treatment Goals for Waldenström Macroglobulinemia?

What Are the Treatment Goals for Waldenström Macroglobulinemia? 

Current Waldenström Macroglobulinemia Treatment Approaches

Current Waldenström Macroglobulinemia Treatment Approaches 


Transcript:

Katherine:

What are you excited about when it comes to Waldenstrom’s research? 

Dr. Sarosiek:

So, there a couple of things that I find really exciting right now. One thing in particular is currently for treatment for Waldenstrom’s, we often use BTK inhibitors. So, the group of medications that includes zanubrutinib (Brukinsa), ibrutinib (Imbruvica), acalabrutinib (Calquence). And that class of medications has really revolutionized treatment for Waldenstrom’s. But sometimes patients become resistant to those medications. And there’s a new group in that same class of what’s called BTK inhibitors.  

And those are non-covalent BTK inhibitors. And those drugs actually work often for patients who progress on initial therapy with ibrutinib or zanubrutinib. So that really, I think is game changing. There are some early Non-Covalent BTK inhibitors that are in trials. And I really think it’s going to lead to use of those medications very commonly in the future for Waldenstrom’s. So, that I think is exciting to have a next oral therapy to go to after progression on the current therapies. I’m also excited about new combinations that are being tried in Waldenstrom’s.  

So, using combinations of different oral therapies together that would offer deep responses and also offer a time-limited therapy. Because right now many of our treatments are given indefinitely. And so, offering a limited therapy. So, I think that, and there are many other things I could go on for a long time about this. But there are many things that I think are really exciting and we’re going to be changing the field in the coming years. 

Katherine:

Dr. Sarosiek, what is immunotherapy? Could you define that and also, how does it work to treat Waldenstrom’s? 

Dr. Sarosiek:

So, immunotherapy includes many different types of medications. But these are all medications that either use the patient’s immune system or use something from the immune system, like an antibody to help fight off a cancer. And this plays a huge role currently and I think it will continue to in the future. So, probably the most common immunotherapy that patients are familiar with, with Waldenstrom’s now is rituximab (Rituxan). So, that’s a monoclonal antibody.  

And that’s used in many combinations in Waldenstrom’s and is a very important therapy currently. And that antibody is essentially just goes into where the cancer cells are located and attacks that type of cell.  

But the other immunotherapies that are up and coming – which I think are important for patients to know about – one is CAR-T cell therapy. So, a lot of patients ask me about that. and that’s essentially, a T cell is part of the immune system that every patient has. And what CAR T-cell therapies do is patients can collect from their bloodstream – the physicians can collect T cells and then they modify those T-cells in a way so that they’ll recognized the cancer and attack the cancer.  

And so then, those T cells are given back to the patient and then that T  cell can go and work with the patient’s immune system to destroy the cancer. And that’s been very successful in a lot of other cancers and is being used in Waldenstrom’s now. And I think we’re going to be learning a lot about that and it’s going to be an important part of the future with immunotherapy involved in Waldenstrom’s. Another therapy similar is something called BiTE therapies. So, Bispecific T-cell engagers.  

So, that’s essentially two antibodies together. One antibody kind of pulls in the cancer cell and one antibody pulls in the immune system. So, when that treatment is given to patients it kind of brings the immune system close to the cancer cells. So, your own immune system can help fight off the cancer. So, those are just kind of two of the newer immunotherapies that are up and coming that I think will play an important role in the future in this disease. 

Katherine:

Who is this treatment right for? 

Dr. Sarosiek:

Immunotherapies in general currently we’re using them – currently immunotherapies are being used in patients who have had a relapsed disease. So, they have already had current available therapies, like BTK inhibitors or rituximab. And there are clinical trials that can use CAR-T cell therapy. And there are up and coming trials with BITE therapy. So, right now it’s being used in their relapse setting. But as we learn more about it, it’s possible those we moved earlier on to patients who are earlier in their disease course. 

Katherine:

What kind of side effects should patients be aware of? 

Dr. Sarosiek:

So, the side effects can vary depending on what the therapy is. So, patients who are getting rituximab, the currently available immunotherapy, patients can have infusion reactions. So, as your body is kind of getting used to that monoclonal antibody coming in, you can have a reaction. And in that case, we have to stop the infusion, wait for the side effects to settle down, and then restart.  

Katherine:

What type of side effects would they be? 

Dr. Sarosiek:

So, side effects from rituximab infusions can really vary. In some patients it can be similar to an allergic reaction. So, let’s say itchy throat or a rash or hives. Sometimes it can be pain in the chest or the back or trouble breathing. So, they can really vary. But most of the time, those can – when the infusion is stopped, we can give patients medications like Benadryl or Tylenol to help with symptoms. And then we can restart the Rituximab at a lower rate. And that lower rate allows the patient’s body to kind of get used to the medication and continue on the treatment. So that’s generally the things we watch for with Rituximab. 

Thriving With CLL: What You Should Know About Care and Treatment

Thriving With CLL: What You Should Know About Care and Treatment from Patient Empowerment Network on Vimeo.

What does it mean to thrive with chronic lymphocytic leukemia (CLL)? CLL expert Dr. Catherine Coombs discusses the goals of CLL care, reviews current treatment options, and shares tools for taking an active role in decisions.

Dr. Catherine Coombs is an Assistant Professor of Medicine in the Division of Hematology at The UNC Lineberger Comprehensive Cancer Center. Learn more about Dr. Coombs here.

See More from Thrive CLL

Download Program Guide


Related Resources:

Thriving with CLL Resource Guide

What Are the Goals of CLL Treatment

What Are the Goals of CLL Treatment?

An Overview of CLL Treatment Types

Transcript:

Katherine:

Hello, and welcome. I’m Katherine Banwell, your host for today’s program. Today, we’re focusing on how to live and thrive with CLL. We’re going to discuss CLL treatment goals, and how you can plan an active role in your care.  

Before we get into the discussion, please remember that this program is not a substitute for seeking medical advice. Please refer to your healthcare team about what might be best for you. Well, let’s meet our guest today. Joining us is Dr. Catherine Coombs. Dr. Coombs, welcome! Would you please introduce yourself? 

Dr. Coombs:

My name is Catherine Coombs. I am an assistant professor of medicine at the University of North Carolina. My main patient practice is CLL and SLL patients, which make up probably about 80 percent of the patients I see. I do see a couple other types of leukemia and precursor states as well.  

Katherine:

Thank you so much for taking the time out of your schedule to join us today; we appreciate it.  

Dr. Coombs:

No problem. My pleasure.  

Katherine:

Since this webinar is part of PEN’s Thrive series, I thought we could start with getting your opinion on what you think it means to thrive with CLL? 

Dr. Coombs:

I’d say the first thing that comes to mind when I hear thriving in CLL is my goal for all my patients, which is to live their lives and enjoy their lives, and to not let CLL take over their lives in any way. But it’s of course important to be knowledgeable and educated about how the disease can impact one’s life. But I think there is a lot of education that can also go with that to help individuals continue to enjoy their lives and do most of the activities they like within reason.  

Katherine:

This helps us guide us through the conversation, so thank you for that. Appropriate treatment obviously is part of thriving. Before we get into the specifics of CLL treatment approaches, how would you define treatment goals?  

Dr. Coombs:

The first thing to jump into prior to going into treatment goals is asking the question, “Is treatment even needed?” CLL, in contrast to pretty much most other cancers, is not one of the cancers that needs to be treated immediately.  

At least in 2022, there’s no proven benefit to early treatment. That is being questioned now that we have drugs that are much better tolerated. There are some nice clinical trials asking that question again, “Is early treatment beneficial?” At least what we know now is that is not the case. As it turns out, probably up to a third of patients with CLL never need treatment in their lifetime. That means that the disease progresses along usually at a slow pace, and individuals die from something else: any number of other potential causes of death.  

The other two-thirds plus do need treatment at some point in their lifetime. The goals of treatment kind of depend on the patient. There’s not a one-size-fits-all approach in my view. I think it depends on what is most important to the patient.  

I’ll give two drastic examples just to show how goals can be different. CLL often is a disease of older individuals. The average age of diagnosis is usually around 70 or so. But many patients have the disease for a few years, if not longer, prior to needing therapy. So, one example patient could be an 85-year-old individual who has had the disease for a decade and finally needs treatment. The goals of that patient may be to control disease, but he or she may not be worried about going into a deep remission, and may be very, totally willing to be on a drug. And definitely in order to control the disease, alleviate disease-related symptoms, but perhaps not get into a deep remission.  

The other patient, just to take it to another far extreme, I work in an academic medical center; I see some very young patients which is not the norm in CLL, but it does happen.  

Say it’s a 40-year-old patient. His or her goals may be very different. They may not like the idea of being on an oral therapy indefinitely or until progression. So, the goals for that patient may be different. They may say, “Gosh, I’d like to do something a bit more intense to be able to be off of therapy.”  

So, I think in the end there’s no one-size-fits-all approach. It generally, for my clinic, comes down to a discussion with the patient talking about what their goals are: is it more important to be off therapy for some period of time and they’re willing to sacrifice a bit more intensive of a schedule? Or are they more appealing to be on a regimen that they’re on indefinitely provided that it still provides disease control and alleviation of the disease-related symptoms.  

Katherine:

That leads me to my next question, which is what is the patient’s role in setting care goals? 

Dr. Coombs:

I think they should have a huge role; it should be a shared decision between the patient and their cancer doctor. I think at least as of now, there’s not one proven best therapy. We have a number of therapies that work extremely well. But they differ quite a bit with respect to the schedule, the possible side effects profile, and sometimes in the cost, depending upon the patient’s insurance. 

Knowing that there’s not a superior therapy, I think the best approach would be to discuss all of the therapies that are highly effective, and then compare and contrast what those therapies may look like for the patient and then make a shared decision.  

Katherine:

I have a follow-up question to what we were talking about a moment ago. What would you say to a patient who has a lot of anxiety about having to wait for treatment? 

Dr. Coombs:

The first thing I would say is that anxiety is normal. More often patients are anxious than not because it’s really hard to be told you have a leukemia and that we’re not going to do anything about it. I think that’s really hard to hear. The way that I try to counsel people is that my role as the doctor is to do no harm. If you have a leukemia and there’s no proven way to make you live longer by giving therapy early on, if you’re in that early stage of CLL where you’re asymptomatic, by offering therapy, all I could do is make you worse.  

I could give you a new side effect, I could add a new cost burden – Until I have data to prove that that’s going to make your life longer, which we do not have yet (maybe that will be different five to 10 years from now, but we do not have that yet), I could only hurt you. So, that’s not what I want to do. I want to have you live and thrive.  

The better thing to do, based on what we know now and what we know our therapies can and can’t do is to do the watchful waiting. But the anxiety is normal. Depending on how severe the anxiety is, I have had patients meet with – at least at UNC we have something called the Cancer Center Support Program, which is a group of psychiatrists, psychologists, therapists that can help talk over what it means to have a cancer diagnosis and not necessarily need therapy.  

Then I also provide education on the other health issues that can come up as part of being a CLL patient even on that watchful waiting program. The thing that we talk about the most is the increased risk for infections, which in the era of the COVID pandemic is a major concern. Luckily, we have a lot of ways to decrease the health risk for COVID, whether it’s due to the administration of vaccines, or monoclonal antibodies, which I think we’ll talk about more later.  

There’re a lot of ways that people can live with it. I do think the anxiety is normal. At least in my own practice, I’ve found that most of the time the anxiety lessens with time. Because it becomes a part of who you are. It doesn’t have to be all of who you are: people can live their lives largely the way they did before with a bit of extra knowledge about things that can come up in the future but may never come up at all.  

Katherine:

Let’s walk through the types of treatments that are used today to treat CLL.  

Dr. Coombs:

So, for the non-watch and wait category, that means we are now thinking about therapy. Most of the time that involves a targeted agent.  

We largely are using a lot less in the way of cytotoxic chemotherapy. Not to say there isn’t a role for it, but in my own practice, it’s not something that I have been using in the past several years because it’s highly toxic. It is effective, but it can lead to some long-term toxicities. And it’s also not quite as effective as these new targeted agents. So, those fall into two major classes.  

The first class is a class of drugs called BTK inhibitors. That stands for brutons tyrosine kinase. That’s an important target in the CLL cells, specifically. The CLL cells are a type of B-cell. So, BTK is important for the signaling of both normal and cancerous B-cells. When we use drugs to block that protein, that impairs the CLL cells’ ability to multiply. Then we ultimately are able to control the disease with prolonged administration of one of these drugs.  

There are two FDA-approved BTK inhibitors. The first FDA-approved agent is a drug called ibrutinib. And then the newer agent is called acalabrutinib. There’s another drug that you may have heard of called zanubrutinib. That is not technically yet FDA-approved for CLL, but it is occasionally used given that it is FDA-approved for other lymphomas, and it is within the national cancer center network guidelines for CLL treatment.  

The big benefit of these drugs is they work phenomenally well at controlling the CLL. I would say the major downside is that they do have to be taken indefinitely. So, patients ask, “Am I going to be on it forever?” Well, it depends on what you mean by forever. We generally keep patients on these drugs as long as No. 1 they’re tolerating them, so no bad side effects, and then No. 2 as long as the CLL is staying under control.  

So, for that 85-year-old patient that I gave as an example, forever may be until the rest of their life. Because they can work for six, seven, eight plus years; so, they’re highly effective. Some patients may go on them and then die from something else years down the road. For the younger patients, or patients who progress faster, we would then put them on something else whenever the drug stopped working, provided that they didn’t have a significant side effect to the drug class. So, that’s a big first class.   

The second large subset of therapies is a drug called venetoclax, which we typically combine with an anti-CD20 drug. The one that we use for patients who are getting their first treatment is called obinutuzumab. Venetoclax is a BCL-2 Inhibitor that inhibits this pathway within CLL cells. It’s not unique to CLL cells, but the CLL cells are particularly dependent upon it called apoptosis.  

So, when they get exposed to this drug, the CLL cells just die; they can’t continue living, they die off. So, venetoclax works really exquisitely well at killing off CLL cells. Probably works better when it’s paired with this drug obinutuzumab. That’s how it was approved in the frontline setting: those two drugs together. The big risk of that therapy, essentially, it’s kind of a weird risk, when the CLL cells die too quickly that can cause some problems in the human body because one has to metabolize all the debris left over from these dead cancer cells. The medical term we use for that is Tumor Lysis Syndrome. 

That can actually be fatal if not done in a safe way. Fortunately, when we do it as per the recommendations by the manufacturer, we’ve not had any adverse severe problems from it. It ends up being that the patient has to come in weekly every five weeks to do a slow ramp-up of the drug to kind of slowly kill off the cancer cells so that the body isn’t overwhelmed by the contents of these dead cancer cells.  

The big advantage of this regimen is that because it kills the CLL so well, people can get into very deep remissions. So, instead of being a therapy that people are on indefinitely, it’s designed as a one-year therapy when given as the first therapy. So, it’s one year and then they’re done. People after that are in remission, they’re not on any treatment. They may feel like they don’t have CLL.  

Most of the time the CLL does come back. It depends on does the patient come back for something else? Which does happen when people are older. But it appears that it keeps people in remission for several years. The median, which is how long it takes for half of patients to have their disease come back, the median progression for survival has not yet been reached for the trial that was done using this therapy.  

So, that’s at least three, four plus years that we’ve been able to follow people. So, very attractive in that you’re done and then you just wait for the disease to come back but largely feel good in the interim.  

Katherine:

When is it time to treat? What factors do you look at? 

Dr. Coombs:

There’s pretty well-established guidelines for when treatment is indicated. The international workshop for CLL has these published guidelines, so it’s something you could google. Off the top of my head, the main reasons that I do treatment, which are included in these guidelines, are 1.) If the patient has low blood counts due to the CLL, so that could be anemia or low platelets. 2.) If they have bulky lymph nodes. They actually define bulky as 10 cm. So, that’s pretty big.  

Or, if the lymph nodes are being symptomatic in some way, they’re bothering the patient, they don’t have to be that big. 3.) If the patient has bulky spleen enlargement or if it’s causing symptoms. The spleen is next to the stomach. So, say some patients may not be able to eat a full meal, that’s another reason we could do treatment.  

Another reason is if the CLL is causing constitutional symptoms. Sometimes these are black and white. One is unintentional weight loss of 10 percent or more of the body weight. The one that’s not always black and white is fatigue. Patients can have fatigue from the CLL, but I’ve found often fatigue can be due to other causes. So, that’s something I consider an important job of mine is to make sure we don’t jump into CLL treatment if say, there’s some other cause for the tiredness, such as, say the thyroid’s off or there’s a huge amount of stress due to some other factor outside of the CLL.  

Then, some other constitutional symptoms are CLL can cause fever or drenching night sweats. Those two it’s important to make sure that there’s not a concurrent infection because infections can also cause those symptoms. The last indication is patients with CLL can develop autoimmune cytopenias. That’s when the immune system attacks some component of the blood cells. Most commonly that’s an autoimmune anemia or autoimmune thrombocytopenia. That’s the term for low platelets.  

Usually, we can treat that with steroids or occasionally CD-20 by itself like rituximab to calm down the immune system. However, if those immune-based therapies fail the patient, then we could consider treating the CLL to help fix that problem.  

Katherine:

We received an audience question prior to the program. They asked, “What does it mean to be refractory, and how is that different from relapsing?” 

Dr. Coombs:

I actually just had a conversation about this. I’m not sure that’s formally defined. I have heard one definition suggested is – I think everyone agrees refractory means you did not respond to your last therapy. That’s actually really bad. Most of our therapies work in almost everyone. So, refractory is a term that is generally accepted means no response. So, whatever therapy you’re on, the CLL did not get better, it got worse. That’s refractory.  

Another definition that I’ve heard based on this recent discussion is if you had a short remission duration, such as six months or shorter. Most of the therapies we use should work for quite a while, usually on the order of years. So, some people also consider refractory a short remission duration, six months or shorter.  

Relapse is probably the more common scenario. That’s a patient who has had some type of therapy, but they had a decent response, but that response wore off, more on a normal pace. Again, not on the order of months, but usually on the order of years.   

Katherine:

There’s not necessarily a one-size-fits-all approach to treating CLL, so how do you decide which treatment is right for a patient?  

Dr. Coombs:

I always look at their underlying disease biology. There’s a couple really important tests that I send for all of my CLL patients by the time that they need therapy. The first is to see what their underlying cytogenetics and molecular findings are. There are certain good findings, and then certain bad findings.  

One of the bad findings is having a deletion in the 17th chromosome in the short arm of that chromosome. The chromosomes are the big pieces of DNA within everyone’s cells. There are findings that are common in CLL: a 17p deletion is a poor prognostic feature. There’s a separate test where we can actually identify mutations in a gene called TP53. And these behave largely the same as 17p deletions, so I always check for both. It’s two different tests.  

Often times patients have both of these findings: a 17p deletion and a TP53 mutation. But sometimes you can have the mutation without the deletion and vise versa. That is one finding that’s important when talking about different therapies. The other really important prognostic test is the IGHV gene mutation status. This is another specialized sequencing test. It looks to see if the patient’s heavy chain, if their immunoglobulin protein has undergone something called somatic hypermutation or not.  

It’s actually good to be mutated. What we know about people who are mutated is that they typically have better responses to most therapies and their disease typically is one that grows slower. So, I use those factors and then I have a conversation with the patient. The two main treatment classes that I spoke about – so the BTK Inhibitors, those work actually really well and even the people with these bad prognostic features. So, people with the 17p deletion, people with the TP53 mutation, they can have disease control for six plus years on a BTK inhibitor, which is really good.   

That was not the case a decade ago when we didn’t have these drugs. That’s something that’s been hugely beneficial for our patients. The venetoclax/obinutuzumab regimen, that still works when people have the 17p or the TP53, but it probably doesn’t work as well.  

I’d mentioned the median time for disease to come back hadn’t been reached yet. It had been reached for that poor risk subset. The expectation for people with that poorest marker is that the median PFS, progression-free survival. So, again, when after someone starts therapy, when the disease then progresses is 49 months. It kind of gives me a rough estimate of, “Gosh, these are your therapy options and based on your underlying biologic factors unique to your disease, this is what you can expect out of therapy A or therapy B.”  

The mutated or unmutated IGHV, similarly, those BTK inhibitors work extremely well, even in people with the bad unmutated finding. I think those are always an option. The other treatment is an option, but the people with that bad finding do have a shorter time until they progress of just under five years.  

Katherine:

Dr. Coombs, why should patients feel confident in speaking up and being a partner in their care? Do you have any advice for helping them find their voice? 

Dr. Coombs:

Great question. I think a patient is their own best advocate. We as their physicians always try to advocate for them, but we often don’t know what their wishes and desires are. I think through speaking to what’s important to you, that can help me know a little more about what path we should take. There’s not always one right path.  

I’ve talked about these two great treatment options we have. I had one patient who loved fishing and he just didn’t want to be in the infusion center. That’s the person that should go on the oral drug, where he doesn’t have to come to and from as often. 

If you tell us about your goals and your desires, that helps us also be your top advocate because then we have a little more background for what’s important to you. I think that’s my main thought. We’re here for you, but we need to know what you value the most. We don’t always know that.  

Katherine:

When should a patient consider a second opinion or a consultation with a specialist? 

Dr. Coombs:

I never discourage a second option. I’m a CLL specialist, but I’ve had patients ask for a second opinion. I’m always enthusiastic about it. If a patient feels that they need another set of eyes on their case. I’ve learned some things from some of my patients who have seen specialists in different areas of the country or locally. We have Duke down the street. Sometimes different providers just have different perspectives.  

Or, sometimes the patient just needs to hear something again if it doesn’t sound right to them. I’ve had patients for example who are one watchful waiting who really just had trouble believing. “I have leukemia, and you’re really telling me to do nothing.” But then they hear it from someone else and it just helps it sink in. I’d say the answer is anytime. Anytime you think you need another set of eyes on the case.  

But I would say especially for people in the community. I do think there’s a lot of value in seeing a CLL specialist once if it’s something that you’re interested in and your insurance pays. I think the community docs have one of the hardest jobs, and I don’t think I could do it. There are so many different cancers that they have to know about. I think, if anything, I have the easy job; I have one tiny slice of the pie that I know a ton about. Not to say they don’t do great jobs; I’m actually phenomenally impressed with most of the community.  

However, they have so much to know, often you can maybe get a little more of a unique view on CLL by seeing a CLL expert. If that’s in your interest. But certainly not mandatory, especially if your goal is to stay away from doctors.  

Katherine:

COVID is of course another factor that impacts a patient’s ability to fully thrive with CLL in today’s world. Many CLL patients are concerned about the effectiveness of the COVID vaccines and their ability to make enough antibodies to fight the virus. So, what do we know about how effective the COVID vaccines are for people with CLL? 

Dr. Coombs:

The COVID vaccines – we were fortunate in being able to build on some earlier research. Even prior to being able to look at the data for COVID vaccines, there have been studies looking at vaccines in general in CLL. That’s actually been a long-term established issue, which is that based on earlier studies we knew most vaccines were not as efficacious in individuals with CLL compared to people without.  

That’s due to this underlying immune deficiency. Since then, they’ve done studies looking at COVID specifically, and we have found lower rates of production of antibodies in individuals with CLL compared to regular, non-CLL controls. There have been a few different studies looking at this. I think the things that have been seen universally is that the CLL patients that are the most severely affected are those that are actively on therapy or have had recent anti-CD20. The CD20 drugs really wipe out the ability to make antibodies probably for a year, if not up to two years.  

The other drug class that can really hamper the ability to make antibodies are these BTK inhibitors. Then, venetoclax to some extent, it’s often paired with the CD20, so it’s hard to tease out the effect. But it likely hampers the ability to make antibodies as well, but just not as much as the CD20, which it’s often given concurrently with.  

CLL patients who have never had therapy can make a decent amount of antibodies, but still quite a bit less than an age-matched control. So, someone also your age without CLL. That was a lot of data based on the original two vaccine series. The Leukemia Lymphoma Society did a study that I actually referred a lot of my patients to, where they collected samples, looked at antibody levels, and they found that giving the booster did seroconvert a good amount of patients who were negative that then became positive for antibodies.  

That’s one of the reasons I’ve really encouraged the booster. This is now talking about the third shot. Now there’s this whole separate discussion about doing a fourth shot. I think the data’s a little too early to say it’s definitely helpful. But I think it’s certainly unlikely harmful. The vaccines don’t quite work as well. I feel very strongly they’re not harmful.  

Not to say any shot can’t cause some issue occasionally. But I think that’s very, very rare. I always encourage my patients to get the vaccine, but I separately say, “Gosh, I wouldn’t use this as an end-all cure because it may not work at its 100 percent efficacy level due to the underlying CLL, and worse when you’re under treatment.” 

Katherine:

We had another audience member send in a related question: “I’ve heard there is a treatment to help boost COVID antibodies. What is it and how can I get access to it?” 

Dr. Coombs:

I was going to bring that up actually, then I figured there was probably another question coming. I’m hugely enthusiastic about the drug that this person is speaking about. It’s called Evusheld. E-V-U-S-H-E-L-D. It got this emergency use authorization designation in December of 2021, so it’s pretty new. The idea behind this drug is that “Gosh, we know that not everyone is going to mount an effective immune response to vaccines, based on their own immune system, inability to make good levels of antibodies.”  

So, it’s two antibodies that were manufactured as this drug. So, it’s a drug that’s actually two different antibodies. It ends up being in two different vials, so you get two shots. It provides really remarkable protection against COVID. They’re long-acting antibodies, so they last for six months.   

The publication from the study that led to this being released showed an approximately 80 percent reduction in COVID for the people who got the shot as opposed to the people who got the placebo.  

Katherine:

It sounds like patients could ask their doctors about where they might be able to access this? 

Dr. Coombs:

Yeah. I think the best person to ask would be your CLL doctor. Because the drug, unless things have changed recently, it’s largely being focused for immunosuppressed individuals. Primary care doctors may not necessarily know a lot about it, but most oncologists are the ones who should have access to it. So, I would say ask your CLL doctor. If you’re in a smaller site that doesn’t have it, they may know in your geographic region where it could be gotten. 

Katherine:

As we close out this conversation, Dr. Coombs, I wanted to hear why you feel patients should be hopeful about the potential to thrive with CLL? 

Dr. Coombs:

There’s just so many reasons to be hopeful. CLL, I’d say more than – obviously it’s the cancer I’m focused on, but I think more than almost any other cancer has had advances that have really changed the lives of our patients in the last decade. And that’s only going to get better.  

We have therapies that work phenomenally well and can get you into remission, get the CLL under control, and let you just live your life as you wish; almost as though the CLL is not there. Though, it is in the background and your doctor can counsel you on special precautions needed. The drugs we have are phenomenal, but we only use them when we need them. Again, we don’t want to give you something you don’t need. But when you need it, the options we have are really phenomenal and they work well.  

They have some side effects, but I’d say they’re much better than the side effects of the older fashion drugs we used to use a decade-plus ago. The disease is there, we have better ways to control it, and I think there’s plenty of reasons to live your life, enjoy your life, thrive. We’ll take care of the CLL with all these tools in our toolbox when we need to.  

Katherine:

Dr. Coombs, thank you so much for joining us today.  

Dr. Coombs:

It’s been my pleasure, thank you.  

Katherine:

And thank you to all of our partners. To learn more about CLL and to access tools to help you become a proactive patient, visit powerfulpatients.org. I’m Katherine Banwell. Thanks for joining us 

Understanding Biomarker Testing for Non-Small Cell Lung Cancer Treatment

Understanding Biomarker Testing for Non-Small Cell Lung Cancer Treatment from Patient Empowerment Network on Vimeo.

 Dr. David Carbone reviews how mutations found through biomarker testing – genetic analysis of the lung cancer – may affect non-small cell lung cancer therapy decisions.

Dr. David Carbone is a medical oncologist and professor of internal medicine at The Ohio State University. Dr. Carbone is also co-leader of the Translational Therapeutics Program at the OSUCCC – James, where serves as director of the Thoracic Oncology Center. Learn more about Dr. Carbone, here.

See More From INSIST! Lung Cancer

Related Resources:

Fact or Fiction? Busting Myths About Non-Small Cell Lung Cancer

Why Non-Small Cell Lung Cancer Patients Should Speak Up About Symptoms and Side Effects

Why Non-Small Cell Lung Cancer Patients Should Speak Up About Symptoms and Side Effects

Immunotherapy for Lung Cancer Treatment: What to Expect

Immunotherapy for Lung Cancer Treatment: What to Expect


Transcript:

Katherine:

Let’s talk about biomarker testing. What is it, first of all, and what are you looking for, exactly, when you receive the results?

Dr. Carbone:

Well, you have to order the results, so you have to know what to order. And we already touched on it a little bit. The genetic analysis of a tumor has become central to picking a therapy. And when I say “genetic analysis,” that is what you’re referring to as one of the biomarker tests we use.

Unfortunately, it’s true that many patients have therapies started without waiting for the results of these biomarker tests, and that really can have a negative impact on their care, because the results of this testing can make the difference between chemotherapy or a pill. It’s a totally diametrically different therapy.

So, these genetic tests look for things that we call driver mutations, and these are alterations in the genes of your cancer that are not present in the rest of your body; they’re not passed down to your children, or need to get looked for in your brother or your sister, like some of the breast cancer mutations you may hear about.

These are mutations that are present in the tumor that act like light switches, and they turn the cancer on to grow like crazy.

And through scientific research, we’ve discovered many of these in lung cancer, where, if we can find the specific driver mutation, many of these have specific drugs that can turn that switch back off. And virtually 100 percent or very close to every patient where we can find that matching drug to their driver will have some tumor shrinkage.

And it’s quite remarkable, but we need to do that matching, because these new drugs only work in that subset of patients with that mutation, and that’s why it’s so important to do that matching. And now, we have eight or 10 of these types of mutations that need to be looked for.

Why Non-Small Cell Lung Cancer Patients Should Speak Up About Symptoms and Side Effects

Why Non-Small Cell Lung Cancer Patients Should Speak Up About Symptoms and Side Effects from Patient Empowerment Network on Vimeo.

Dr. David Carbone, a lung cancer expert, emphasizes the importance of speaking up, advocating for yourself, and being an active member of your non-small cell lung cancer health care team. 

Dr. David Carbone is a medical oncologist and professor of internal medicine at The Ohio State University. Dr. Carbone is also co-leader of the Translational Therapeutics Program at the OSUCCC – James, where serves as director of the Thoracic Oncology Center. Learn more about Dr. Carbone, here.

See More From INSIST! Lung Cancer

Related Resources:

What Treatments Are Available for Non-Small Cell Lung Cancer?

How Is Non-Small Cell Lung Cancer Staged?

Immunotherapy for Lung Cancer Treatment: What to Expect

Immunotherapy for Lung Cancer Treatment: What to Expect


Transcript:

Katherine:                  

Patients can sometimes feel like they’re bothering their healthcare team with their comments and questions. Why is it important for patients to speak up, and become a partner in their own care? 

Dr. Carbone:              

So, it’s a fact that when patients get the diagnosis of lung cancer, everything changes in their lives. They suddenly have a whole new vocabulary thrown at them. It’s like their doctor is speaking French to them. They have to trust their life to a person they’ve never met before, and a whole cadre of people coming in and talking to them and poking them and running through scanners. 

It’s very difficult for someone whose biggest concern was what to make for dinner that night, and now has a diagnosis of lung cancer, to really comprehend what’s going on. And lung cancer is complicated, so I recommend that patients really try their best to have at least a basic understanding of what’s going on, where their cancer is. I always show the patient their scans.  

“Your cancer is here; this is what it looks like; that’s why you’re having that pain over there, because you have this spot here. Your genetic testing shows this and this, and that’s why it’s important, and that’s why we’re using this drug to match this mutation.” And these are things patients will understand if doctors will explain it to them.  

And similarly, the side effects. Lung cancer patients tend to be tough people. They’ll say, “It’s not so bad, I feel better; but the side effect is not so bad. I’m just not going to tell them.” And it even happens in clinic that they’ll tell me they feel fine, and then they’ll tell the nurse that they hurt in their left elbow. And I have to go back in and ask them some more questions on that.  

So, it’s extremely important to feel comfortable in communicating with your doctor, asking questions; “Why am I getting this scan? Why are we using this treatment? Is this the best treatment? Are there clinical trials available? I have this new symptom, x, y, z,” because symptoms are often much easier to treat when you catch them early than when you catch them late.  

And you don’t get a medal for being a tough guy in this situation. Tell your doctor if you have pain, and they can manage it. Tell them if you’re short of breath, and they can help you feel better. They can’t help you if you don’t tell them, and you are your own best advocate in this situation. Ask questions about the treatment, and why that’s the best one for you; and, as I said, about clinical trials. 

Katherine:                  

Excellent. Thank you so much. It’s important for people to remember that.  

What Is Maintenance Therapy for Non-Small Cell Lung Cancer?

What Is Maintenance Therapy for Non-Small Cell Lung Cancer? from Patient Empowerment Network on Vimeo.

Lung cancer expert Dr. David Carbone responds to a patient question about the purpose of maintenance therapy for lung cancer and what to expect.

Dr. David Carbone is a medical oncologist and professor of internal medicine at The Ohio State University. Dr. Carbone is also co-leader of the Translational Therapeutics Program at the OSUCCC – James, where serves as director of the Thoracic Oncology Center. Learn more about Dr. Carbone, here.

See More From INSIST! Lung Cancer

Related Resources:

What Treatments Are Available for Non-Small Cell Lung Cancer?

Why Non-Small Cell Lung Cancer Patients Should Speak Up About Symptoms and Side Effects

Why Non-Small Cell Lung Cancer Patients Should Speak Up About Symptoms and Side Effects

Immunotherapy for Lung Cancer Treatment: What to Expect

Immunotherapy for Lung Cancer Treatment: What to Expect


Transcript:

Katherine:

Lindsay sent in this question: “My doctor has talked about putting me on maintenance therapy following my treatment regimen. What is maintenance therapy for lung cancer?”

Dr. Carbone:              

So, many of our treatments have a maintenance phase, and I’m not sure which treatment she’s talking about. But even with chemotherapy, now, if people are on chemotherapy alone, will usually use a double chemotherapy to start, and then will drop one of the chemos after a few cycles, and then continue the other as a maintenance.

A more typical regimen today is a combination of two chemos and an immunotherapy. And generally, we’ll stop the more toxic chemotherapy after a few cycles and continue the less toxic chemotherapy plus the immunotherapy, usually for up to two years.

After chemo-radiation, you’d have a maintenance immunotherapy as well. So, maintenance therapy is just a lower-intensity therapy after your initial therapy, designed to keep the cancer from coming back.

Immunotherapy for Lung Cancer Treatment: What to Expect

Immunotherapy for Lung Cancer Treatment: What to Expect from Patient Empowerment Network on Vimeo.

Dr. David Carbone responds to a viewer question related to the symptoms, side effects, and efficacy of immunotherapy for non-small cell lung cancer.

Dr. David Carbone is a medical oncologist and professor of internal medicine at The Ohio State University. Dr. Carbone is also co-leader of the Translational Therapeutics Program at the OSUCCC – James, where serves as director of the Thoracic Oncology Center. Learn more about Dr. Carbone, here.

See More From INSIST! Lung Cancer

Related Resources:

What Treatments Are Available for Non-Small Cell Lung Cancer?

How Is Non-Small Cell Lung Cancer Staged?

What Is Maintenance Therapy for Non-Small Cell Lung Cancer?


Transcript:

Katherine:

We have received some questions from audience members earlier on. And so, David writes, “My care team has suggested immunotherapy to treat my lung cancer. I’m optimistic about the results, but nervous about symptoms and side effects. What can I expect?”

Dr. Carbone:              

The immunotherapy is a potent therapy, but you have to understand, you’re dealing with lung cancer, which is a rapidly fatal disease when untreated. So, there’s a balance there. There’s a risk/benefit calculation that happens in picking any treatment.

And it turns out that I would say most lung cancer patients today have immunotherapy as part of their first treatment. Immunotherapy ramps up your own immune system to make it more effective at seeing the cancer, which has previously grown because it’s hidden itself behind a kind of invisibility cloak, and these immunotherapies remove this invisibility cloak so that the immune system can see it.

But at the same time, this process is a normal process that’s used to keep the immune system in check, and keep the immune system from attacking normal tissues, as well. So, it’s pretty common that we see people on immunotherapy have some kind of autoimmune side effect.

The most common side effect with immunotherapy is a skin rash, and usually it’s mild, and you just treat it with a topic corticosteroid, and it’s not a big issue. But it sometimes can be very severe. Like everything else, there’s a spectrum. I would say most patients have no skin problems; some have severe; and it’s almost always treatable. The next most common side effect is thyroid endocrine disorders. So, people will get thyroid function loss. And so, this is something that we follow carefully in the clinic, and people who are on immunotherapy.

And when we start seeing their thyroid levels going down, we just start them on thyroid medication, and that completely fixes that problem. So, but it’s usually permanent, and even after they stop immunotherapy, they’ll need to take thyroid medicines and adjust their thyroid levels.

And then, there’s a whole slew of other possible side effects that are less common. Some are very severe. Less than one percent of patients have a severe side effect called colitis, which causes diarrhea, which can even be life-threatening, but is also treatable if detected early. Very uncommon to be so severe, but patients should let their doctors know if they experience unusual diarrhea.

You can also have inflammation in your lungs called pneumonitis. So, if there’s an onset of shortness of breath, of course, you’ll tell your doctor, and that can be treated, as well. And anything else, there’s a huge list of other things. Arthritis, uveitis, other things that happen, but are pretty rare.

What Treatments Are Available for Non-Small Cell Lung Cancer?

What Treatments Are Available for Non-Small Cell Lung Cancer? from Patient Empowerment Network on Vimeo.

 Dr. David Carbone provides an overview of currently available treatments for non-small cell lung cancer patients, including clinical trials, and reviews factors that influence treatment decisions.

Dr. David Carbone is a medical oncologist and professor of internal medicine at The Ohio State University. Dr. Carbone is also co-leader of the Translational Therapeutics Program at the OSUCCC – James, where serves as director of the Thoracic Oncology Center. Learn more about Dr. Carbone, here.

See More From INSIST! Lung Cancer

Related Resources:

Fact or Fiction? Busting Myths About Non-Small Cell Lung Cancer

How Is Non-Small Cell Lung Cancer Staged?

Immunotherapy for Lung Cancer Treatment: What to Expect

Immunotherapy for Lung Cancer Treatment: What to Expect


Transcript:

Katherine:

What are the current approaches for treating non-small cell lung cancer?  

Dr. Carbone:

Well, that’s a complex question. The basic modalities are surgery, which is really still what we prefer, if we can detect it early; radiation therapy; and medical therapy.  

And medical therapy can be divided into chemotherapies of some sort – what we call targeted therapies, based on genetic abnormalities in the tumor – and then, immunotherapies to harness the immune system to fight cancer. Those are the three major kinds of therapies.  

Katherine:

It seems like patients really do have a lot of options, which is a good thing for them. But how do you then decide which treatment is most appropriate for a given patient? 

Dr. Carbone:

Well, it’s not straightforward. When I started 35 years ago, it really wasn’t clear whether any treatment made any difference, and we actually did a large, randomized trial of doing nothing versus treating, and showed that we could improve survival by a month or two with the currently available treatments. Now, we have a huge toolbox of types of treatments and combinations of treatments. And it really requires a careful analysis of the characteristics of the tumor to pick the best therapy.  

And specifically, for the adenocarcinomas, the most common type, we now do a detailed genetic analysis on all of the tumors, which can completely change the type of treatment people get and the prognosis, and result in being able to match a pill-type targeted therapy to a particular genetic abnormality with really high efficacy and low toxicity. And there are other markers we use for immunotherapy choices. It’s become quite complicated.  

Katherine:

Where do clinical trials fit in, Dr. Carbone?  

Dr. Carbone:

Well, I like to say that clinical trials are tomorrow’s standard of care available today, and all of the new treatments that I’m talking about for lung cancer that have made this dramatic difference in survival and quality of life: They’ve all come because of basic science research, understanding how cancers grow, designing drugs, and using them in people in an intelligent way.  

Historically, we used to just grind up tree bark or dig things up from the bottom of the sea, and test them in tissue culture to see if they killed cancer cells a little more than normal cells. But today, the treatments we have are based on science, and the success of these treatments is very high compared to what they were historically.  

And the way we determine whether a treatment is effective is through something called a clinical trial, where generally the new treatment is compared to the standard treatment.  

And if there is no standard treatment, we still do sometimes use placebo-controlled trials, but often that’s placebo plus some chemotherapy, versus the new drug plus that same chemotherapy.  

So, it’s really not a placebo-only type situation. But the trials are designed to rigorously test whether the drug improves outcomes, and are an extremely important step in developing these new drugs and finding new things to help patients.  

Expert Advice for Navigating Non-Small Cell Lung Cancer Care and Treatment

Expert Advice for Navigating Non-Small Cell Lung Cancer Care and Treatment from Patient Empowerment Network on Vimeo.

Dr. David Carbone, a lung cancer specialist, discusses factors to consider when choosing treatment for non-small cell lung cancer (NSCLC). Dr. Carbone provides and overview of the type of treatment for NSCLS, why biomarker testing is essential, and shares advices for playing an active role in your care.

Dr. David Carbone is a medical oncologist and professor of internal medicine at The Ohio State University. Dr. Carbone is also co-leader of the Translational Therapeutics Program at the OSUCCC – James, where serves as director of the Thoracic Oncology Center. Learn more about Dr. Carbone, here.

Download Guide

See More From INSIST! Lung Cancer

Related Resources:

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

How Are Targeted Therapy and Immunotherapy Used in Lung Cancer Care?

What Key Tests Impact Lung Cancer Treatment Choices

What Key Tests Impact Lung Cancer Treatment Choices?


Transcript:

Katherine:                  

Hello, and welcome. I’m Katherine Banwell, your host for today’s program. Today, we’re going to discuss how you can insist on the best care for your non-small cell lung cancer.  

Before we get into the discussion, please remember that this program is not a substitute for seeking medical advice.

Please refer to your healthcare team about what might be best for you. All right, let’s meet our guest today. Joining me is Dr. David Carbone. Dr. Carbone, welcome. Would you please introduce yourself?

Dr. Carbone:              

Thank you, Katherine. It’s a pleasure to be here. I’m David Carbone. I’m the director of the thoracic oncology center at Ohio State University in Columbus, Ohio. And I have a 35-year clinical and research interest in lung cancer, and I’m a medical oncologist myself.

Katherine:                  

Excellent, thank you. Thank you for joining us today. Before we get into our discussion, which will focus on non-small cell lung cancer, let’s talk about the types of lung cancer. What is the difference between non-small cell lung cancer and small cell lung cancer?

Dr. Carbone:              

Well, I like to tell patients every cancer is different from every other cancer, but they can be broadly categorized in two different categories, small cell and non-small cell.

And this derived from decades ago when small cell lung cancer just looked different under the microscope than non-small cell lung cancer. And different small cells can look different, and now we’re sub-typing small cells. But in general, small cells are treated pretty similarly. Non-small cells are divided into two main groups, the squamous cell carcinomas and the adenocarcinomas.

Adenocarcinomas have a variety of subtypes, as well, and then there are a few of the non-small cell lung cancers that are clearly non-small cell but don’t fit into either of those two categories, and they’re called large-cell or not otherwise specified.

And then, there’s a whole slew of rare types of lung cancers that we probably don’t have time to discuss, and mesothelioma that happened in the chest.

Katherine:                  

Right. Is one type of lung cancer more common than the other?

Dr. Carbone:              

So, the vast majority of lung cancers are the non-small cell lung cancers, about 85 percent. And among the non-small cell lung cancers, most of those are adenocarcinomas or non-squamous. Decades ago, squamous was the most common type, and in some parts of the world, it still is. But in the United States, it depends on the region; 60, 70 percent of lung cancers are adenocarcinomas.

Katherine:          

Right, okay, that makes sense. I’d like to pivot and talk about treatment for a couple of moments. What are the current approaches for treating non-small cell lung cancer?   

Dr. Carbone:          

Well, that’s a complex question. The basic modalities are surgery, which is really still what we prefer, if we can detect it early; radiation therapy; and medical therapy.

And medical therapy can be divided into chemotherapies of some sort – what we call targeted therapies, based on genetic abnormalities in the tumor – and then, immunotherapies to harness the immune system to fight cancer. Those are the three major kinds of therapies.

Katherine:                  

It seems like patients really do have a lot of options, which is a good thing for them. But how do you then decide which treatment is most appropriate for a given patient?

Dr. Carbone:              

Well, it’s not straightforward. When I started 35 years ago, it really wasn’t clear whether any treatment made any difference, and we actually did a large, randomized trial of doing nothing versus treating, and showed that we could improve survival by a month or two with the currently available treatments. Now, we have a huge toolbox of types of treatments and combinations of treatments. And it really requires a careful analysis of the characteristics of the tumor to pick the best therapy.

And specifically, for the adenocarcinomas, the most common type, we now do a detailed genetic analysis on all of the tumors, which can completely change the type of treatment people get and the prognosis, and result in being able to match a pill-type targeted therapy to a particular genetic abnormality with really high efficacy and low toxicity. And there are other markers we use for immunotherapy choices. It’s become quite complicated.

Katherine:                  

If we’re breaking it down to staging, let’s start with that. What are the stages?

Dr. Carbone:              

Right. So, lung cancer, like many cancers, is staged I, II, III, and  IV, and of course there’s now As, Bs, and Cs, and subcategories of those. But the basic distinction patients need to know has some utility.

So, the stage I lung cancers, in general, are small tumors that aren’t invading into anything, that haven’t spread anywhere to none of the lymph nodes, to no other structures; and they’re the tumors that we like to find. And they’re the ones whose optimal treatment is surgery, with a good cure rate.

Stage IIs, in general, are those lung cancers that are like stage I, except they involve the nearby lymph nodes in the lung that are called hilar lymph nodes, and those have also a high cure rate, but not quite as so high with surgery; and generally, are treated with surgery followed by chemotherapy, and now, immunotherapy.

Stage III is what we call locally advanced. It’s still only in the chest, but it invades some important structure or has multiple lymph nodes that are deep within the chest. And some of these are surgically resectable, but the majority of stage IIIs, I would say, are not surgically resectable, and are treated generally with chemoradiation, again followed by immunotherapy.

With the stage IV lung cancers, really, that is the lung cancer that’s spread outside the chest; typically, to bones, brain, or liver, or elsewhere in the body.

And that is typically not resectable; though again, there’s exceptions to each of these general rules, and you really need to have that multi-disciplinary evaluation of your cancers to determine the best therapy. But in general, stage IV lung cancers are not surgical candidates, not treated upfront as radiation candidates, and they’re generally treated with medical treatments that go throughout the body, and treat spots of cancer wherever they are.

Katherine:                  

How about when we look at general health and comorbidities? How do those influence the treatment choices that you would make?

Dr. Carbone:              

Every patient is different, like every cancer is different, and we have patients who are 20-year-olds and patients who are 90-year-olds; and patients who’ve taken care of themselves, and those that haven’t done so well taking care of themselves.

More than half of patients, even though they used to smoke, are ex-smokers. And so, they generally are in better condition, but we have to take into account frailty and presence or absence of diabetes, kidney disease, and all those other comorbidities, which are common in lung cancer, which has a median age of onset in the upper-60s, where people have these kinds of comorbidities.

We try not to use age alone as a factor, because there are many robust 90-year-olds, and there are many 50-year-olds on oxygen. So, we have to look at the complete picture to plan the best therapy.

Katherine:                  

Yeah. What about treatment side effects? How does that bear on what you decide to treat the non-small cell lung cancer?

Dr. Carbone:    

Well, unfortunately, we don’t cure most lung cancers. And so, our treatments are designed to prolong life and improve quality of life.

So, we’re very aware of the impact of our treatments on the quality of a patient’s life, and we’ve worked hard, over the years, to improve the risk-benefit ratio of our treatments, so to speak. And again, when I started, we didn’t have good nausea medicines, and people got desperately sick to have a six-week prolongation in survival, and that was really of questionable utility.

But now, even the chemotherapies that we give are generally super-well tolerated. The chemotherapies used in lung cancer are often – people will say, “I feel a little tired for a couple of days, but then, I’m fine,” and they’d often continue to work. Most, I would say, have no nausea; they have no significant side effects; and the immunotherapies, on average, people have very few side effects. They can hardly tell they’re getting the treatment, though sometimes the side effects can be significant.

Like everything I’m telling you, there’s always a spectrum.

Katherine:                  

Of course.

Dr. Carbone:              

And the targeted therapies: Again, most often, people have very mild side effects, with maybe a little skin rash or a slight loose stool, or something. But often, it’s insignificant compare to the magnitude of the benefit they get from these treatments.

Katherine:                  

Let’s talk about biomarker testing. What is it, first of all, and what are you looking for, exactly, when you receive the results?

Dr. Carbone:              

Well, you have to order the results, so you have to know what to order. And we already touched on it a little bit. The genetic analysis of a tumor has become central to picking a therapy. And when I say “genetic analysis,” that is what you’re referring to as one of the biomarker tests we use.

Unfortunately, it’s true that many patients have therapies started without waiting for the results of these biomarker tests, and that really can have a negative impact on their care, because the results of this testing can make the difference between chemotherapy or a pill. It’s a totally diametrically different therapy.

So, these genetic tests look for things that we call driver mutations, and these are alterations in the genes of your cancer that are not present in the rest of your body; they’re not passed down to your children, or need to get looked for in your brother or your sister, like some of the breast cancer mutations you may hear about.

These are mutations that are present in the tumor that act like light switches, and they turn the cancer on to grow like crazy.

And through scientific research, we’ve discovered many of these in lung cancer, where, if we can find the specific driver mutation, many of these have specific drugs that can turn that switch back off. And virtually 100 percent or very close to every patient where we can find that matching drug to their driver will have some tumor shrinkage.

And it’s quite remarkable, but we need to do that matching, because these new drugs only work in that subset of patients with that mutation, and that’s why it’s so important to do that matching. And now, we have eight or 10 of these types of mutations that need to be looked for.     

Katherine:                  

Where do clinical trials fit in, Dr. Carbone?

Dr. Carbone:              

Well, I like to say that clinical trials are tomorrow’s standard of care available today, and all of the new treatments that I’m talking about for lung cancer that have made this dramatic difference in survival and quality of life: They’ve all come because of basic science research, understanding how cancers grow, designing drugs, and using them in people in an intelligent way.

Historically, we used to just grind up tree bark or dig things up from the bottom of the sea, and test them in tissue culture to see if they killed cancer cells a little more than normal cells. But today, the treatments we have are based on science, and the success of these treatments is very high compared to what they were historically.

And the way we determine whether a treatment is effective is through something called a clinical trial, where generally the new treatment is compared to the standard treatment.

And if there is no standard treatment, we still do sometimes use placebo-controlled trials, but often that’s placebo plus some chemotherapy, versus the new drug plus that same chemotherapy.

So, it’s really not a placebo-only type situation. But the trials are designed to rigorously test whether the drug improves outcomes, and are an extremely important step in developing these new drugs and finding new things to help patients.

Katherine:                  

A lung cancer diagnosis often has a certain stigma associated with it, but the majority of that is not based in fact. So, I’d like to play a little game with you called Fact or Fiction. All right? All right, first one. Fact or fiction: Lung cancer is a disease of the older population.

Dr. Carbone:              

If you have lungs, you can get lung cancer. That’s it. I’ve seen 20-year-old lung cancer patients. So, I think it can happen to anybody, and unfortunately, things like the CT screening programs are limited to people over the age of 50, but I’ve had many patients in their 30s and 40s. So, if you have lungs, you can have lung cancer.

Katherine:                  

Okay. Next one, fact or fiction: Quality of life is greatly diminished after undergoing treatment for lung cancer.

Dr. Carbone:              

I completely – fiction. I actually tell people often their quality of life is dramatically improved after starting treatments, and that’s my goal.

And with the new treatments, that’s often true. People will tell me within a week that they feel so much better on the treatment than they did before. So, that’s our goal. Our goal is not to make you feel worse. Our goal is to make you feel better.

Katherine:                  

Of course. All right, last one. Fact or fiction: There are no effective treatments for advanced lung cancer.

Dr. Carbone:              

So, the average survival for lung cancer years ago was four to six months from the time of diagnosis to death. That’s bad. And now, we are seeing in these subsets of patients years and years of survival with simple even pill-type treatments or immunotherapies. And even with the immunotherapies, sometimes you get treatments for a year or two, and then we stop; and we have patients who are years later, off of all treatments for metastatic lung cancer, still with no evidence of disease.

So, that is definitely fiction. We have highly-effective treatments for lung cancer. But unfortunately, like everything else, and like I’ve said multiple times, it’s not true for everyone. Our treatments aren’t ideal. Sometimes for a particular patient we can’t find a matching treatment, the standard treatments don’t work, and nothing we can find makes a difference. But I would say you never know that until you try, and for the vast majority of patients, we can definitely give them prolonged, good-quality life. And so, I think that that’s definitely fiction.

Katherine:                  

Okay, thank you. We have received some questions from audience members earlier on.

And so, David writes, “My care team has suggested immunotherapy to treat my lung cancer. I’m optimistic about the results, but nervous about symptoms and side effects. What can I expect?”

Dr. Carbone:              

The immunotherapy is a potent therapy, but you have to understand, you’re dealing with lung cancer, which is a rapidly fatal disease when untreated. So, there’s a balance there. There’s a risk/benefit calculation that happens in picking any treatment.

And it turns out that I would say most lung cancer patients today have immunotherapy as part of their first treatment. Immunotherapy ramps up your own immune system to make it more effective at seeing the cancer, which has previously grown because it’s hidden itself behind a kind of invisibility cloak, and these immunotherapies remove this invisibility cloak so that the immune system can see it.

But at the same time, this process is a normal process that’s used to keep the immune system in check, and keep the immune system from attacking normal tissues, as well. So, it’s pretty common that we see people on immunotherapy have some kind of autoimmune side effect.

The most common side effect with immunotherapy is a skin rash, and usually it’s mild, and you just treat it with a topic corticosteroid, and it’s not a big issue. But it sometimes can be very severe. Like everything else, there’s a spectrum. I would say most patients have no skin problems; some have severe; and it’s almost always treatable. The next most common side effect is thyroid endocrine disorders. So, people will get thyroid function loss. And so, this is something that we follow carefully in the clinic, and people who are on immunotherapy.

And when we start seeing their thyroid levels going down, we just start them on thyroid medication, and that completely fixes that problem. So, but it’s usually permanent, and even after they stop immunotherapy, they’ll need to take thyroid medicines and adjust their thyroid levels.

And then, there’s a whole slew of other possible side effects that are less common. Some are very severe. Less than one percent of patients have a severe side effect called colitis, which causes diarrhea, which can even be life-threatening, but is also treatable if detected early. Very uncommon to be so severe, but patients should let their doctors know if they experience unusual diarrhea.

You can also have inflammation in your lungs called pneumonitis. So, if there’s an onset of shortness of breath, of course, you’ll tell your doctor, and that can be treated, as well. And anything else, there’s a huge list of other things. Arthritis, uveitis, other things that happen, but are pretty rare.

Katherine:                  

Lindsay sent in this question: “My doctor has talked about putting me on maintenance therapy following my treatment regimen. What is maintenance therapy for lung cancer?”

Dr. Carbone:              

So, many of our treatments have a maintenance phase, and I’m not sure which treatment she’s talking about. But even with chemotherapy, now, if people are on chemotherapy alone, will usually use a double chemotherapy to start, and then will drop one of the chemos after a few cycles, and then continue the other as a maintenance.

A more typical regimen today is a combination of two chemos and an immunotherapy. And generally, we’ll stop the more toxic chemotherapy after a few cycles and continue the less toxic chemotherapy plus the immunotherapy, usually for up to two years.

After chemo-radiation, you’d have a maintenance immunotherapy as well. So, maintenance therapy is just a lower-intensity therapy after your initial therapy, designed to keep the cancer from coming back.

Katherine:                  

Right. Okay. We have one other question, this one from Shelley: “Is lung cancer hereditary? I’m curious if my children should undergo genetic counseling, since I was diagnosed with lung cancer.”

Dr. Carbone:             

Well, that’s a simple, complicated question.                                   

So, in general, lung cancer is not hereditary. It’s not like familial breast cancer or ovarian cancer, or those kinds of cancers, or retinoblastoma. Most cases of lung cancer are caused by environmental exposure to cigarette-smoking or radon, and are not passed on to your kids genetically, though there is shared exposure, right?

There are some really rare genetic predispositions that we sometimes find on these biomarker panels.

But the vast, vast majority of lung cancers are not heritable, and you don’t need to worry about your kids, except to tell them not to smoke, and test for radon.

Katherine:                  

Patients can sometimes feel like they’re bothering their healthcare team with their comments and questions. Why is it important for patients to speak up, and become a partner in their own care?

Dr. Carbone:              

So, it’s a fact that when patients get the diagnosis of lung cancer, everything changes in their lives. They suddenly have a whole new vocabulary thrown at them. It’s like their doctor is speaking French to them. They have to trust their life to a person they’ve never met before, and a whole cadre of people coming in and talking to them and poking them and running through scanners.

It’s very difficult for someone whose biggest concern was what to make for dinner that night, and now has a diagnosis of lung cancer, to really comprehend what’s going on. And lung cancer is complicated, so I recommend that patients really try their best to have at least a basic understanding of what’s going on, where their cancer is. I always show the patient their scans.

“Your cancer is here; this is what it looks like; that’s why you’re having that pain over there, because you have this spot here. Your genetic testing shows this and this, and that’s why it’s important, and that’s why we’re using this drug to match this mutation.” And these are things patients will understand if doctors will explain it to them.

And similarly, the side effects. Lung cancer patients tend to be tough people. They’ll say, “It’s not so bad, I feel better; but the side effect is not so bad. I’m just not going to tell them.” And it even happens in clinic that they’ll tell me they feel fine, and then they’ll tell the nurse that they hurt in their left elbow. And I have to go back in and ask them some more questions on that.

So, it’s extremely important to feel comfortable in communicating with your doctor, asking questions; “Why am I getting this scan? Why are we using this treatment? Is this the best treatment? Are there clinical trials available? I have this new symptom, x, y, z,” because symptoms are often much easier to treat when you catch them early than when you catch them late.

And you don’t get a medal for being a tough guy in this situation. Tell your doctor if you have pain, and they can manage it. Tell them if you’re short of breath, and they can help you feel better. They can’t help you if you don’t tell them, and you are your own best advocate in this situation. Ask questions about the treatment, and why that’s the best one for you; and, as I said, about clinical trials.

Katherine:

Excellent. Thank you so much. It’s important for people to remember that.                   

And I just want to remind our audience that you can send in your questions to question@powerfulpatients.org, and we’ll get them answered, hopefully, on future programs.

So, Dr. Carbone, just to wrap things up, what are you excited about in lung cancer research right now, and what would you like to leave the audience with?

Dr. Carbone:              

Well, there’s a lot to be excited about in lung cancer right now. There’s new therapies being approved all the time. We have more new approvals in the last few years than in the last few decades put together. So, there’s a lot to be excited about.

But there’s still a lot of room for improvement, and there are a lot of patients who still suffer and die from lung cancer. So, my message to patients would be to make sure they get their biomarker testing before they start treatment. And it doesn’t mean to get the tests sent off and start on Joe Random treatment, until the test comes back. This means wait until the test comes back before starting treatment.

And then, I would recommend getting second opinions, if a patient is in a private practice without availability of clinical trials, to investigate if there might be new clinical trials available for them; again, before starting treatment, because sometimes even that first dose of standard chemo may make you ineligible for a trial. So, No. 1 is biomarkers.

Katherine:                  

All right. Thank you so much for joining us today.

Dr. Carbone:              

Well, you’re very welcome. Thank you for helping patients better understand how to deal with this disease.

Katherine:                  

And thank you to all of our partners.

To learn more about lung cancer and to access tools to help you become a proactive patient, visit powerfulpatients.org. I’m Katherine Banwell. Thanks for joining us today.

How Will You Know if Your Lung Cancer Treatment Is Working?

How Will You Know if Your Lung Cancer Treatment Is Working? from Patient Empowerment Network on Vimeo.

How do lung cancer experts determine if a treatment approach is working? Expert Dr. Heather Wakelee explains how treatment effectiveness is monitored and what should be analyzed when treatments stop working.

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.

See More From INSIST! Lung Cancer

Related Programs:

 
What Are the Goals of Lung Cancer Treatment?

What Are the Goals of Lung Cancer Treatment?

How Are Targeted Therapy and Immunotherapy Used in Lung Cancer Care?

How Are Targeted Therapy and Immunotherapy Used in Lung Cancer Care?

What Are the Advantages of Newer Lung Cancer Treatment Approaches?

What Are the Advantages of Newer Lung Cancer Treatment Approaches?

Transcript:

Katherine:

We have a question that we received from an audience member earlier. Jeff asks, “How do you know if your lung cancer treatment is working?”

Dr. Wakelee:

So, there are a lot of ways of knowing if treatment is helping. So, the one I rely on the most is, “Does the patient overall feel better?” That is difficult to say exactly how. Sometimes people are having breathing problems; they feel that that’s better. Sometimes their energy’s lower. They feel better. It can be vague. We also use scans. So, we tend to get scans, depending on the treatment we’re giving, every couple of months plus or minus, sometimes, every three months to help track what’s actually going on. But occasionally, there are discrepancies.

So, sometimes, the scan, is it better? Is it not better? Can’t really tell. And then, you’re always taking that, “How does the patient feel?” So, usually, if the scans are better, the patient feels better. It’s easy. Usually if the patient’s feeling worse and the scan looks worse, clear decision. Not a good one, but clearly, we need to do something different. But sometimes, you’re left, and especially this happens with the first scan because you get a scan, it takes a little while, you start the new treatment, then you get the next scan, how much of the changes happened before you started the new one and how much didn’t? So, these can be more challenging conversations, but generally if the patient’s feeling a little bit better, the scan’s unclear, we usually say, “You know, let’s give this treatment a little bit more time.” We also, I think your question was specifically around how do we tell if it’s working, but you also often need to be thinking about, “Well, what’s it doing that’s negative to the person and is that potential, those side effects worth the benefits we are or are not seeing?”

So, it’s kind of all of those things together. It can be a bit complex.

Katherine:

What goes into the decision to change therapies if it becomes necessary?

Dr. Wakelee:

So, when we’re thinking about making a change, the way I always look at it is, is where we are today still okay or not? And, if it’s not, that would be because clearly the cancer’s growing or clearly the side effects are just not tolerable. Then, we decide together with the patient we need to do something different. And, when we think about what do we do next, we look at what have we’ve already done, did it work or not, if not, let’s do something more different. And so, let’s think about something that might be somewhat similar. When we’re dealing with targeted therapies, we have ways to try to figure out what changed in the tumor that made it now resistant or not working with that treatment.

And so, with some of the pill drugs, there’s been a lot of research and understanding how does the tumor change that helps it evade, get away from, be resistant to whatever treatment you’re on.

And then, sometimes, we have other pill drugs that work in that particular setting, not always. With immune therapy, we’re trying to better understand why does the immune therapy stop working?

Sometimes you can add back to it, like, you can add chemotherapy back to immune therapy alone or sometimes you can do radiation with immune therapy to get that response back. Or, add other combinations to it. So, that’s another thing that we’re working on. And then, like I said, if someone hasn’t ever had chemotherapy and the tumor’s become resistant, we’re going to be thinking a lot about chemo because that can play a role against so many different reasons that the cancer might not be responding to whatever treatments someone’s on. And then also, looking at how the patient’s feeling and doing, what their overall what we call “performance status, ” their sort of overall health, and how well do we feel with them that they’re going to be able to tolerate the next treatment because, you’re always having to weigh how much is this likely to help, and how might this harm in finding the right balance. 

What Are the Advantages of Newer Lung Cancer Treatment Approaches?

What Are the Advantages of Newer Lung Cancer Treatment Approaches? from Patient Empowerment Network on Vimeo.

Lung cancer expert Dr. Heather Wakelee shares insight about how newer treatments, such as targeted therapy and immunotherapy, impact quality of life and patient outcomes.

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.

See More From INSIST! Lung Cancer

Related Programs:

 
How Are Targeted Therapy and Immunotherapy Used in Lung Cancer Care?

How Are Targeted Therapy and Immunotherapy Used in Lung Cancer Care?

What Key Tests Impact Lung Cancer Treatment Choices

What Key Tests Impact Lung Cancer Treatment Choices?

Lung Cancer Treatment Decisions What Should Be Considered

Lung Cancer Treatment Decisions: What Should Be Considered?

Transcript:

Katherine:

Right. What are the advantages of these new treatment approaches compared to standard chemotherapy?

Dr. Wakelee:

Well, I think the most exciting news that we’ve seen in lung cancer over the last few years is that we’re actually helping more people live longer. And the way that we’re doing that is through these newer treatments. So, when we can personalize treatment by recognizing that a person’s cancer has a specific gene mutation and we can give them the right targeted pill drug, we can help them live longer and feel better because those often have fewer side effects. Wish I could say they were curing the disease, but they’re helping people live longer.

And, that can be measured in years for some folks, which is fantastic. And then, with immune therapy, again, they’re not working for everybody, but they were for a large number of patients with lung cancer with non-small cell to help them live longer with their cancer controlled. And so, we’ve actually improved the overall survival rates for lung cancer with these new developments. Where we can make even more of an impact is also by finding more of the cancers earlier, and that’s where cancer screening is so important also. So, by having more choices, chemotherapy can still help a lot of people. Targeted therapies can help probably close to 20, 30, 40 percent of people with non-small cell lung cancer that’s the adenocarcinoma type.

And then, the immune therapies can help other people living with lung cancer. Usually immune therapies don’t work on the same tumors the way the targeted pills work. So, you’re kind of getting at different groups of people with those different strategies. It’s not completely true, but it’s a kind of general principle about it.

Katherine:

What about side effects for some of these treatment choices?

Dr. Wakelee:

So, chemotherapy is one people fear the most, but I think it has a bit more of a bad reputation than it needs. A lot of the lung cancer therapies that are chemotherapy can be reasonably tolerated. I mean, I’m not signing up to go get chemotherapy just because. There definitely are side effects. The biggest one is people get fatigue, get really tired. Though, if they’re feeling horrible because of the cancer, a lot of times people feel dramatically better. But, tiredness, it can impact appetite a little bit, though cancer does that also. There can be nausea, vomiting, but we’re much better at controlling that with the newer drugs. Some cancer therapies cause hair loss, but a lot of our non-small cell lung cancer therapies don’t cause hair loss. So, there are a lot of options there you can talk about with your doctor. And then, when the blood counts are low, there can be risk for infection, low red blood cells with anemia.

So, there are a lot of different things. But in general, chemotherapy is better tolerated than people think it’s going to be because in the movies, they make it look horrendous.

With the pill therapies, again, lots of variability depending on the specific pill. Some of them cause rash. Some don’t. Some of them can cause some changes to the heart that we have to monitor with EKGs, electrocardiograms, some don’t. Some cause some changes to labs like for liver tests that we have to monitor. Some don’t. Some cause hair color changes. Some don’t. It’s always to gray, unfortunately.

So, there are a lot of different variations in what different treatments can do. And so, it’s just really important if your doctor is talking with you about starting one of the targeted pill drugs that you really ask what are the side effects I need to be watching for, what are the ones I need to know to call you about, and which are the ones I just know, “Okay, this is happening and it’s okay. It’s going to cause swelling in the ankles,” no, just a huge range of them. And then, with the immune therapy drugs, they tend to be mostly fatigue, just like with chemotherapy, though some people feel fine.

What we have to watch for is that they can cause what we call autoimmunity. So, it’s talking about the fact that the way they work is they help the immune system better recognize the cancer, and they do that by taking away one of the stop signals. But that stop signal, the PD-1, PD-L1, that stop signal is also used by a lot of normal cells to tell the immune system to back off.

So, when you remove it, when you block it, the immune system can get confused and start to attack normal cells. So, you can get a rash, people can end up with gut symptoms like diarrhea, they also can end up with it attacking the lungs and causing what we call a pneumonitis lung inflammation or brain symptoms, so, almost anything. Now, those are rare, and we can treat them with steroids. But, people need to be aware that if something new is happening, they need to alert their doctor. I think sometimes, there’s this false impression that immune therapy is completely safe, but, it’s not. And, all of the treatments that I’m talking about are designed to help people live better and live longer when they’re dealing with lung cancer, but they all also have risk.

And so, it’s just really important to have those discussions with the care team as you’re starting something new about what are the things I need to be watching for and to know how to reach people if you’ve got a new and concerning symptom, especially if you’re starting on something new. 

How Are Targeted Therapy and Immunotherapy Used in Lung Cancer Care?

How Are Targeted Therapy and Immunotherapy Used in Lung Cancer Care? from Patient Empowerment Network on Vimeo.

Expert Dr. Heather Wakelee explains how targeted therapy and immunotherapy work to treat lung cancer and which patient type each therapy is most appropriate for.

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.

See More From INSIST! Lung Cancer

Related Programs:

 
What Are the Advantages of Newer Lung Cancer Treatment Approaches?

What Are the Advantages of Newer Lung Cancer Treatment Approaches?

How Will You Know if Your Lung Cancer Treatment Is Working?

How Will You Know if Your Lung Cancer Treatment Is Working?

Expert Perspective Exciting Advances in Lung Cancer Treatment and Research

Expert Perspective: Exciting Advances in Lung Cancer Treatment and Research

Transcript:

Katherine:

Dr. Wakelee, you mentioned targeted therapies. How do they work?

Dr. Wakelee:

Targeted therapies are something we can use when we find a specific gene mutation in the tumor. So, I mentioned before that in order for a cancer cell to become cancer, something has to happen to the DNA in the cell.

And, there’s a change or a mutation in the DNA of the cell which leads it to be a cancer. And, a lot of the time, that mutation happens in a specific kind of gene that makes a type of protein called a tyrosine kinase. And for those of you who haven’t studied a lot of science, it’s a word you might not have heard before. But basically, these tyrosine kinases are proteins in the body that make a lot of changes to what’s going on in the rest of the cell. So, they’re sort of what we call regulators. And, one way of thinking about them is like on and off switches. So, normally, their job is to sit and if the right molecule comes around, that turns it on, and then it turns on other proteins in the cell. And if that molecule isn’t there, it’s turned off. So, it’s this on and off switch that does a lot of other aspects of what’s going on in the cell. But, sometimes, a mutation happens. It turns it on all the time. So, it’s like if you leave the light on.

It’s on all the time, that’s using a lot of energy, and that’s actually what’s driving the cell to act like a cancer. And so, we can now look for some of those mutations that turn some of these tyrosine kinases on all the time. But we’ve also developed drugs that we can use to turn them off. So, if we find this specific gene mutation that’s turning, say, the EGFR protein on all the time, if we find that, we can have the patient take a pill that then turns that off.

And that helps the cancer slow down, some of it die, some of the cancer cells die, but it doesn’t completely wipe it out. It helps the patient for a long time though by shrinking the cancer, helping them feel better because the symptoms are gone, keeping the cancer from growing. But, cancer cells are clever. They continue to divide, they can continue to make new mutations, and eventually, they figure out ways around that. So, when we talk about targeted therapy, it’s a setting where we find the cancer.

In the cancer, we find the gene mutation, it’s in one of these specific types of proteins, genes that make specific protein that turn something on that we can then turn off, and with those pill drugs, we can have a big impact for people.

Katherine:

And, what exactly is immunotherapy?

Dr. Wakelee:

Immunotherapies are treatments that were used to help keep the immune system more active.

So, the immune system is a very complex mechanism. There are cells that their whole job is to figure out and find things that are not us. So, they are looking for bacteria, they’re looking for cells that have a virus in them, and when they find it, they attack. And, that attack can be in the form of antibodies, it can be cells that actually go in and attack other cells directly, and we are all familiar a little bit with the immune system because we know that if we get a cold, our body, we can get a fever, that’s part of our immune response, and we get better. And then, some people know the bad side of the immune system if they have allergies or certain autoimmune diseases where the immune system gets a little bit too revved up and starts to recognize normal things as foreign.

So, in the setting of cancer, normally, the immune system is able to recognize a cancer cell, see that it’s different from the rest, and get rid of it. But, cancer cells are clever and they figure out ways to evade the immune system. And, one of the ways they do this is they put a protein called PD-L1. So, PD-L1 is a protein that a lot of our normal cells use to say, “Just a normal cell. Ignore me.”

And so, when an immune cell comes in and sees that, it gets turned off it goes away. So, what our immune therapies do is most of them are blocking that PD-L1 protein. And, when they do that, it’s sort of like taking away the stop sign. So, you’ve got a tumor using a stop sign to say, “Go away, immune cell,” you block it so the immune cells can’t see that stop sign, and so then it kills the cancer cell better. So, that’s how these drugs work, and that’s the immune therapy.

There are some other stop signs besides PD-1 and PD-L1, but that’s the most common. So, when we’re talking about immune therapy, it’s drugs that block that. So, they increase the ability for the immune cell to recognize cancers. The risk from them is that you can get the body to recognize normal tissue as a problem sometimes. So, that’s the toxicity that we watch for. 

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.

See More From INSIST! Lung Cancer

Related Resources:

Accessing Personalized Treatment for Lung Cancer

Lung Cancer Treatment Decisions What Should Be Considered

Lung Cancer Treatment Decisions: What Should Be Considered?

In-Depth Testing for Lung Cancer Prognosis and Treatment

In-Depth Testing for Lung Cancer Prognosis and Treatment


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. 

In-Depth Testing for Lung Cancer Prognosis and Treatment

In-Depth Testing for Lung Cancer Prognosis and Treatment from Patient Empowerment Network on Vimeo.

How is in-depth lung cancer testing used in determining lung cancer prognosis and treatment? Expert Dr. Heather Wakelee shares insight about biomarker testing, genomic testing, and how test results may impact treatment options.

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.

See More From INSIST! Lung Cancer

Related Programs:

 
Lung Cancer Treatment Decisions What Should Be Considered

Lung Cancer Treatment Decisions: What Should Be Considered?

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

How Are Targeted Therapy and Immunotherapy Used in Lung Cancer Care?

How Are Targeted Therapy and Immunotherapy Used in Lung Cancer Care?

Transcript:

Katherine:

Dr. Wakelee, but what is genomic or biomarker testing?

Dr. Wakelee:

So, we are struggling with how to have one unifying way of describing it because it’s so complicated. So, to me, biomarker testing is any aspect of the tumor that helps us choose the best treatment for that patient. And so, it’s a very broad term. And, within biomarker testing, there are several different ways that we look at it.

So, one is to look at what proteins are on the cell’s surface. And, we do that by having stains that we use to stain the tissue. So again, complicated, but when a piece of tissue is taken out of the person, part of the tumor is removed. It’s sliced into little tiny slices, which are then put on glass slides that can be looked at under the microscope. And, that’s how the pathology doctors can look and see, “Ah, this looks like cancer,” or, “It doesn’t look like cancer.” When it does look like cancer, you can then put on stains, so basically, different colored antibodies that will light up if that particular protein is there. And so, that helps us figure out for sure that this started in the lung because there are specific proteins that are only found in lung. So, that’s one way we used it, and this is an older technology. But we also can use that to look for how much of this PD-L1 protein is expressed.

And so, that’s an important biomarker, but it’s not based on genomics, which is when we’re talking about the DNA.

Then, we have the genomic testing, and that’s when we’re looking at the genome of the tumor and how that genome is different. And, that’s that DNA or RNA testing. We talk about it with the next-gen sequencing. So, “sequencing,” any of those terms are all meaning we’re looking at some aspect of what makes the tumor genes and therefore the proteins made by the tumor different than the rest of the genes in the person.

And so, that testing, that genomic testing can be done on either the tumor specimen or that’s where we can do blood tests that will be able to pull out those bits of the DNA that are from the tumor versus from the person and help us figure out what’s going on with the cancer. So, when we talk about biomarkers, the whole picture, and when I’m talking with patients who are diagnosed with lung cancer, we talk about well, there’s chemotherapy treatment, which is good for almost everybody. There is targeted therapy.

Targeted therapy is usually based on those genomic tests, and the genomic tests can be done either on the tissue or on blood. But, they’re really important to have a full understanding of the

tumors to do a comprehensive or next-gen sequencing analysis of the tumor or DNA. And then, you have the immune therapy where that PD-L1 biomarker is important. So, that’s the way I think about it, and the biomarkers are really critical for helping us figure out what’s the best path forward for any individual patient.

When I started treating lung cancer patients 20 years ago, we only had chemotherapy. And now, for metastatic disease, with using the right biomarkers, we can figure out so much more about the cancer to be able to personalize the treatment, for many patients, being able to offer pill therapies that are somewhat less toxic and highly active and give people more time. And now, we’re in the immune therapy revolution, which is helping a whole other group of patients living with lung cancer to be able to live with quality life for much longer. And the pace of discovery is just going up so quickly. And, I think that’s what I’m most hopeful about is just how much attention is being paid on lung cancer and finding better therapies that are going to help more people for a longer period of time.