How Do We Increase Precision Medicine’s Reach in Lung Cancer?

Living Well With Lung Cancer

In this webinar in partnership with H. Lee Moffitt Cancer Center & Research Institute, Dr. Jhanelle Gray, a medical oncologist, Dr. Stephen Rosenberg, a radiation oncologist, and Dr. Theresa Boyle a molecular pathologist will discuss the latest understanding of lung cancer research; currently approved therapies and promising clinical trials.

Downloadable Guide


Transcript:

Andrew Schorr:   

And greetings from here, San Diego-Carlsbad, California. I’m Andrew Schorr from Patient Power. Welcome to this Patient Empowerment Network program. I am so excited. It is really a wonderful opportunity for anybody dealing with lung cancer. Whether you’re the patient or you’re a close friend or a family member, to get the latest information.

So, let’s meet that team. I wanna start with a medical oncologist and that is Dr. Jhanelle Gray. And she is director of thoracic clinical research in the Department of Thoracic Oncology at the Moffitt Cancer Center. Dr. Gray, thanks so much for being with us.

Dr. Gray:                

Thank you very much. It’s a pleasure to be here.

Andrew Schorr:   

Okay. We’re gonna understand the role of the medical oncologist. But it’s a bigger team than that. So, I wanna also have us meet Dr. Stephen Rosenberg who is a radiation oncologist and works in concert with medical oncology. He’s normally down in Tampa, but today – where are you in Wisconsin, Dr. Rosenberg?

Dr. Rosenberg:    

I’m currently in Madison, Wisconsin giving a talk later today and tomorrow. 

Andrew Schorr:   

Okay. Home of the University of Wisconsin. Thanks for joining us.

And then there’s another member of the medical team none of us usually get to meet. And that is the pathologist who’s looking at our biopsy. Whether it’s taken from the lung or now increasingly liquid biopsies, our blood, and we’re gonna talk about that. And that is a pathologist and that is Theresa Ann Boyle who joins us. Dr. Boyle, thank you for being with us.

Dr. Boyle:               

Thank you for inviting me. It’s nice to be dragged out from behind the scenes.

Andrew Schorr:   

All right. Well, you won’t be beside the scenes anymore.

And of course, all of this – we have this whole group, but it doesn’t mean anything unless there’s a patient that they can help and maybe a family with them. So, let’s meet a patient from Tampa who’s been living with lung cancer for a number of years, Ed Cutler. Ed, thank you so much for joining us on this program and we’re gonna share your story. Hi, Ed.

Edward Cutler:     

Hi. It’s a pleasure to be here and an honor to be honest with you.’

Andrew Schorr:   

Well, Ed, so, you’ve been living with lung cancer how many years now? 

Edward Cutler:     

Just over five years.

Andrew Schorr:   

Okay. But let’s face it, it wasn’t that long ago if somebody was told they had lung cancer they were not long for this world with more advanced lung cancer. So, modern medicine has made a big difference for you, hasn’t it?

Edward Cutler:     

It certainly has. When I received my diagnosis, I was given the quote average life expectancy statistics and they didn’t look very good.

Andrew Schorr:   

Right.

Edward Cutler:     

So, I went the whole way.

Andrew Schorr:   

And we should mention that for the last couple years you’ve been in a clinical trial and it’s an immunotherapy. And we’re gonna talk about immunotherapy along the way. We’re gonna talk about target therapies, immunotherapies. The doctors are gonna help us understand this whole idea of precision medicine. Which means, “How do you get what’s right for you?”

And you’ve had some changes along the way, right Ed? I mean there you are in Tampa continuing your work as a tax consultant, I know. And been married more than 50 years to Donna, which is great. Children and grandchildren. But you’ve had kind of a journey that’s had changes along the way, right?

Edward Cutler:     

It has been a journey. Yeah. Yeah. Initially I started out with standard of care chemotherapy. And that basically took over 16 months. Basically, the first two or three months I was on the full medication of three drugs. And then they dropped off one and then I was on maintenance. But at the end of the 16th month they discovered that there was a new tumor. And I was told I was now chemo-resistant and that was the end of chemotherapy for me.

So, my etiologist and I sat down, and we started searching. And at that point, I don’t think there were any other approved medications. Everything else I think was still in trials at the time. Now I know that there are maybe two, three, a half a dozen medications that are out of trials and FDA-approved. But at that time, I was limited to clinical trials. And Dr. Tan, who is my oncologist, gave me the options looking at two or three different trials. And my goal was to live as long as possible with good quality of life. And that’s what I was looking for in each of the trial descriptions.

And we ended up selecting one and I took all of the various testing to qualify for that trial and I was ultimately accepted. It was a two-drug combination of infusion. And unfortunately, I only lasted seven – roughly seven months in that trial because of side effects that almost killed me. 

Andrew Schorr:   

But now there’s another trial?

Edward Cutler:     

And fortunately, it took another few months, but we located another trial that was being performed only at Moffitt. I said, “Well, that’s convenient.” So, I said, “Yeah.” Everything looked good on that. Sure, there were potential side effects, but I was willing to take my chances with it. And here I am nearly three years into that trial and I’ve been stable most of that three-year period. There was a little bit of tumor size reduction initially and basically stable the rest of the time. It’ll be three years come the end of January.

Andrew Schorr:   

That’s such great news.

So, Dr. Gray, you have lots of trials at a major center like Moffitt, maybe you could just tell us in this world of lung cancer, patients who participate in trials have not only paved the way for everybody, but it’s given them great hope, hasn’t it?

Dr. Gray:                

Absolutely. So, we have a lot of trials at Moffitt. We try to organize ourselves within a way of doing a personalized medicine approach. And basically, that means that any patient that comes to Moffitt we wanna give them the best treatment possible. And many times, that is a clinical trial. With clinical trials a lot of times you have access to more novel agents and things that you can’t necessarily get through your regular route through FDA approval. And also, a lot of that work is spurred by research developed here at Moffitt and partnering with the basic science researchers as well as us at a lot of the clinical – on the clinical side and making sure that we move these drugs forward and into the clinic for patients.

And Edward, I just wanna say I’m very happy about your story. And thank you for taking the time today to be with us and to share your journey with us. And give us your perspectives to this too.

Andrew Schorr:   

Yes. It’s very inspiring to all of us. And Ed, we know you’re a golfer. And so, you’ve been… 

Edward Cutler:     

Well, I was.

Andrew Schorr:   

Well, please God you can do that and travel with Donna. And the main thing is you are with us.

Dr. Gray:                

Yes.

Andrew Schorr:   

And I know that means so much to you and your family.

We’re gonna talk about the team approach as we go forward. So, Dr. Rosenberg, radiation oncology comes into play here because often when somebody’s diagnosed radiation can help shrink the tumors, right? And also alleviate some of the pain and other issues that people may have, right?

Dr. Rosenberg:    

Yeah. No. I think you hit on a lot of big major points there. And it really is a team approach. Particularly at Moffitt when we approach lung cancer trying to think about how we can do best for the patients, whether it’s a clinical trial or not. Radiation plays a big role for patients who have a locally advanced disease. Some of the standard of care is combining chemotherapy with radiation for patients with some advanced disease. But for patients who have had cancer spread to other parts of the body as well, radiation’s really good to help alleviate pain and even approve breathing and the other things that are happening.

And with newer agents we often find that radiation may even be potentiating the immune effects of some of the new immunotherapy drugs that are out there. And so, we’re really excited about some of the trials and studies we’re doing with Dr. Gray and her team. And the team as a whole at Moffitt combining irradiation with some of their new – with targeted drugs and immunotherapy drugs right now.

Andrew Schorr:   

Wait. Let me see if I get that. And Dr. Gray, feel free to comment too. Are you saying that radiation can sort of boost the effect of some of these medicines?

Dr. Rosenberg:    

Yeah. There is a lot of anecdotal evidence out there. And some basic science that’s right now emerging about how the immune system and radiation really are so interconnected. And how that helps us actually attack cancer by actually basically releasing the immune system to recognize the cancer in the body. And so, by combining that with immunotherapy drugs we’ve really found our ability to potentiate some of the effects of these immunotherapies.

Most of this is basic science. There are some anecdotal case reports out there with some of the newer drugs that have just come out in the last year or two FDA-approved have been after chemoradiation and we think they really work together well. And some of the newer trials at Moffitt are gonna be trying to combine these things up front. And I know Dr. Gray has been helping to lead that effort with Dr. Perez and others within our kinda joint departments here.

Dr. Gray:                

Yes. Absolutely. And so that work that Dr. Rosenberg was just talking about was actually developed at Moffitt. So, there’s a trial out there that’s now published in the New England Journal of Medicine. It led to the FDA approval of a drug called Durvalumab, which is actually named because the company, AstraZeneca, wanted to add durable responses and add value to patients. So, Durvalumab is where the name came from, interestingly enough.

And the study, what we wrote, was to look at those patients getting chemotherapy plus radiation therapy completing what’s considered standard of care therapy for those patients with that particular type of non-small cell lung cancer. And following this with an immunotherapy agent, the durvalumab (Imfinzi), for one year. And it significantly improved the outcomes for patients. Patients are living much longer when we utilize this method.

And now this has become the standard here in the United States. It’s working its way through the approval mechanisms over in Europe and through other companies. And I think this has really revolutionized how we approach and treat patients. And we are looking at – now we know it’s safe to give them sequentially. And so, can we safely and effectively – meaning can we actually improve outcomes for patients by moving these therapies upfront?

And so, it would be giving a lot of therapies together. So, it would be chemotherapy plus immunotherapy plus radiation therapy to patients. But at the end of the day, the goal here is to improve our outcomes in a – and still maintain quality of life for patients. So, it’s always challenging pushing the bar and reaching these goals for our patients.

[Crosstalk]

Andrew Schorr:   

Right. Right.

So, Ed, just a little bit more about your story and then we’re gonna bring Dr. Boyle into this too as we talk about personalized medicine. So, when you were originally diagnosed, you were, I think, consulting with a doctor about a concern about an aortic aneurism. It had nothing to do with cancer.

Edward Cutler:     

Yeah.

Andrew Schorr:   

You went to one doctor and then maybe a GI specialist. That’s where they found a mass. And then you went to Moffitt and saw a lung cancer specialist. Did I get that right?

Edward Cutler:     

That’s right. Yeah. The triple-A test, the Abdominal Aortic Aneurism test, was negative. But down at the bottom of the report in the footnote was that they saw a mass in my liver and follow-up was recommended. So, we went from there. I went to my primary care and he referred me to a GI doc and they pretty much agreed that there was some kind of cancer, but they didn’t know what exactly. They recommended that I get a PET scan, which Medicare would not permit. They said you have to have a diagnosis before you can get a PET scan.

So, the alternative was to have the biopsy. I said, “Okay. But let me get a second opinion first.” And that’s when I came out to Moffitt and they confirmed everything. I had my biopsy here at Moffitt. And there was a tumor in my liver, but the biopsy traced it back to my lung. Therefore, I have lung cancer.

Andrew Schorr:   

Right. And I wanna explain that. Okay. So, let’s start with Dr. Boyle on that. So, Dr. Boyle, you look at the biology of tissue samples or sometimes blood.

Dr. Boyle:               

Correct.

Andrew Schorr:   

And so, somebody says, “Oh, I have liver cancer.” But that just came up where he said well, he didn’t really have liver cancer, he had cancer that originated in the lung and the biology of it was it needed lung cancer treatment, right? And that’s part of what you figure out, right?

Dr. Boyle:               

Right. Right. Right. And actually, within the pathologist group there’s different fields of pathology. There’s the anatomic pathology where they’re looking at the diagnosis, “Is it lung cancer origin or is it kidney cancer origin?” I’m in the field of molecular pathology. So, I’m looking at the genetic changes inside the tumor, or in the blood too, and I’m trying to understand what those changes might mean in terms of what would be the best therapy for the patient. I’m also in the lung cancer research field. So, trying to better understand all of these immune checkpoints and how can we look at them. Why do some patients respond, and others don’t respond?

So, pathology is a large field. So, I’m working very closely with the thoracic department. In fact, I belong to them. 50% of my job is with the lung cancer department and 50% with the pathology department. And we found that that was helpful because the field is expanding so dramatically. Even within every year there’s great advances. And for anyone to keep up with everything is too difficult these days. And so, we really do all work as a team here at Moffitt. And so, as Jhanelle and I talk back and forth – a lot of emails with.

Dr. Gray:                

Right. Yes.

Dr. Boyle:               

So, I even consulted them on some of these questions you have. So, it’s great.

[Crosstalk]

Andrew Schorr:   

All right. Well, we’re gonna delve into this personalized medicine world. And the doctors will help us understand. We’ll understand how it applies to patients like Ed or others who may be watching. So, let’s put up the personalized medicine slide. Kat is our director and she’ll put it up.

I have a little dog barking here. I’m sorry.

Dr. Gray:                

No, you’re fine.

Andrew Schorr:   

Very cute.

Dr. Boyle:               

I like dogs.

Andrew Schorr:   

Kat, if you could put up this slide? There we go. Okay. So, help us understand – let’s start with you, Dr. Boyle.

Dr. Boyle:               

Yeah.

Andrew Schorr:   

This whole wheel around the right, what is this alphabet soup there? What is it?

Dr. Boyle:               

Right. Right. Right. So, this is showing the variety of different genes that can have genetic changes in the tumor. And it’s focused on the genetic changes that have potential clinical action or proven clinical action. EGFR is probably a more familiar one because that one came out first with better responds to EGFR inhibitor therapy than chemotherapy and others have come along. Like with ALK, ALK inhibitor therapy works well. With MEK, XM14 has become important, MET amplification.

Andrew Schorr:   

Okay. These are genes that have gone awry that are driving someone’s cancer, right?

Dr. Boyle:               

Correct. Right. Right. Right. And this wheel is trying to pick up on the driver mutations. There’s even more genes not on this wheel here that are passengers. Other mutations that might have some specs, but they might not necessarily be causing the tumor or driving the tumor but might be worth considering in terms of the therapy. In immunotherapy, tumor mutations burden has been something we look at. And they’re looking at many, many gene changes to see if there are more mutations than usual. And when that occurs, there might be a better likelihood of response to immunotherapy. So, we’re learning more and more everyday about all of these genes and more.

Andrew Schorr:   

Okay. We’re gonna define this. And Dr. Gray, you can help us. These kinda big bubbles to the right.

Dr. Boyle:               

Yes.

Andrew Schorr:   

So, first of all, a myth: All lung cancer tumors are the same. This right here says, “No,” right?

Dr. Gray:                

No. Absolutely. Yes. The fact is that each patient’s tumor has a unique biology. And the wheel on the left I think really helps to define this. That at the end of the day when we get a patient we’re concerned about, we get a biopsy, get a piece of tissue, send it over to pathology to Dr. Boyle’s team. She’s not only looking under the microscope to help us with, “What’s the diagnosis? What’s the origin of the tumor?” But we also wanna look at, “What is driving your tumor?”

And so, how I’ve explained it to patients is in two ways. You have a computer that has all these different parts, but at the end of the day what drives the computer is really that hard drive. And if you open up the hard drive there’s this little piece of hardware that’s actually making everything run. And that’s what we’re doing with the tumors is going into the cell, looking at the DNA level and seeing what is turning on your specific tumor.

Another way of thinking about it is as a hub for an airline, for example. So, a lot of us know Delta has a very big hub in Atlanta. They have a lot of flights that go through there. But if you were to shutdown Atlanta you would significantly impact the feasibility of Delta being able to function.

And that’s what we’re doing by looking at these driver mutations. We wanna find what’s turning on your tumor and then match that patient to the correct medicine. So, if you have the EGFR mutation, I wanna give you an EGFR inhibitor. If you have an ALK rearrangement, I wanna give you an ALK inhibitor. If you have a MEK mutation, I wanna give you a drug that targets MEK. What I don’t wanna do is if you have an EGFR mutation give you an ALK inhibitor. I’m doing you a disservice.

And so, it is very important – I think you brought up a very good point at the beginning of this that the team approach for lung cancer is imperative so that we can all work together to get the right patient the right treatment at the right time. 

Andrew Schorr:   

We’re gonna look at a graphic for that in just a second. I wanna just go over a couple of other things you mentioned. So, somebody might have a lung biopsy. Get some tissue. That goes to Dr. Boyle and her colleagues.

Dr. Gray:                

Yes.

Andrew Schorr:   

Wherever in the world you get treatment. And they’re taking a look at it to see where in this wheel – what comes up for them?

Dr. Gray:                

Correct.

Andrew Schorr:   

And then also there’s a – in that purple bubble there it says, “Tumor testing can happen at any point.” And so, we talked about driver genes.

Dr. Gray:                

Yes.

Andrew Schorr:   

And then Dr. Boyle mentioned passenger genes.

Dr. Gray:                

Yes.

Andrew Schorr:   

Well, they can change over time, right? 

Dr. Gray:                

Correct.

Andrew Schorr:   

There’s an argument for having testing again at some later time, right?

Dr. Gray:                

Absolutely. And so, for example, if you have an EGFR mutation and I give you an EGFR inhibitor, you then have a chance that your tumor can mutate against that specific drug that I’m giving you. And you can acquire a different mutation. And so, how do I know what’s going on? I need to get more tissue or – I don’t know when we’re planning on talking about it, but this is a good segue into liquid biopsies.

So, a liquid biopsy is getting a blood sample from patients and looking – specifically looking again at this wheel, looking at those mutations to see if we can identify them.

Andrew Schorr:   

Okay. 

Dr. Gray:                

And so, it is very, very important to keep monitoring patients, getting their blood, getting their tissue over time so we can make educated decisions. Again, just to relate this to something I think we’re all very familiar with is infections. If you keep giving the infection the same antibiotic, what happens? It develops resistance. And these drugs are no different and cancer’s no different. It’s just we have to stay ahead of the game and try to keep trying to outsmart the tumor.

Andrew Schorr:   

Right. Right.

[Crosstalk]

Dr. Gray:                

So, absolutely monitoring.

Andrew Schorr:   

Many researchers and specialists talk about cancer being really a wilily enemy.

Dr. Gray:                

Yeah. Enemy. Yes.

Andrew Schorr:   

And so, you can knock it back. But there’s sometimes the survival of the fittest of some cells that have some other property, like another gene?

[Crosstalk

Dr. Gray:                

Yes.

Andrew Schorr:   

So, Dr. Boyle, just help us to understand this idea of liquid biopsy. Because I know over the last few years sometimes there’s been a concern – I don’t know who does it. Whether a surgeon does it. Who does it? To get a lone biopsy and as much tissue as they can. But you’re saying, “Well, I need more to make other decisions.” Where does liquid biopsy come in now, basically a blood test, to help inform targeted, well-informed lung cancer care?

Dr. Boyle:               

Right. Right. Yes. Pathologists always want more tissue, but now we have an alternative. And sometimes an alternative gets the results faster back to the oncologist and the patient. And that’s the blood testing. And it has less risk than taking a sample from the lung. Now, the interpretation of the results from the liquid or the blood specimen is a little different than the interpretation from a tissue specimen. And when you get a positive result from the small amounts of cell-free DNA circulating in the blood, you can really count on it. And the oncologist can treat the patient with a targeted therapy based on that.

There are times when the results are all negative and you don’t know if the results are negative because there just wasn’t enough cell-free DNA in the blood or because the tumor is truly negative for all the mutations being checked. And so that’s where it really is important to follow-up with tissue testing. So, it’s been really a great advance in the field to be able to test with a specimen that’s much more easily available and can be tested right away.

Andrew Schorr:   

I’ve had the opportunity to tour foundation medicine back in Boston area and also be in some labs at other hospitals. And I’m amazed that these super sophisticated analyzers now to try to see what’s going on, whether the blood or the tissue

Okay. So, we’re gonna come back to where does that go out? I wonder if Kat, our director, could put up the personalized medicine slide? One more time, Kat. No, not that one. We’re gonna come back to that. That one.

So, there’s that whole area, Dr. Gray, on the left where it says, “Other.” And I know that Dr. Boyle and her colleagues around the world are trying to say, “Well, are there driver genes that we just haven’t identified yet?” And you keep having these analyzers looking at more and more, a bigger – 100, 200, and 300 whatever.

Dr. Gray:                

Yes.

Andrew Schorr:   

But some people, and I think this was Ed’s case. There wasn’t a driver gene that was identified.

Dr. Gray:                

Right.

Andrew Schorr:   

Well, what do you do there? 

Dr. Gray:                

So, one of the things that we’re testing for in addition to these driver mutations is also looking if patients may be a better candidate for immunotherapy and looking at a marker called PD-L1. It’s programmed death-ligand 1 which can be found on the tumor tissue cells. So, most patients will undergo simultaneous testing for both the immunotherapy marker as well as one of these driver mutation markers. So, if we’re unable to find a driver mutation, but we’re able to find that the tumor’s positive for PD-L1, that then triggers to us, as a medical oncologist, that, “Hey. We need to kind of shift and let’s focus on getting the patient immunotherapy.”

And particular now with the approvals and the trials that we’ve participated in here at Moffitt, as well as at other centers, that really if you have lung cancer, you don’t have a driver mutation. Outside of having a specific rational why you shouldn’t get immunotherapy, really you should be starting on immunotherapy.

I just wanna make – within that setting I just wanna make something clear. There are also some patients where you can find a driver mutation and you can find that they’re positive for the marker for the immunotherapy. And how do you choose between the two? For right now, most of the data points toward that you should focus on treating the driver mutation. That that does take precedence over the PD-L1, the marker for immunotherapy, okay?

And I know there’s a lot of commercials out there and a lot of excitement about immunotherapies for very good reason, but I would reserve the immunotherapy in those subsets of patients who have both markers to maybe a later line of therapy. But that also gives you a backup plan, right? It’s to your point you’re always trying to project and sequence things for the patients as much as we can. So, it is helpful to do both markers upfront and then act accordingly.

Andrew Schorr:   

Okay. I wanna make a point. I think that we’re done with this slide now. I wanna make a point that some people – it’s the minority, but it’s still a significant group – don’t have non-small cell lung cancer. 

Dr. Gray:                

Correct. 

Andrew Schorr:   

They have small cell lung cancer. And this has been tougher. But my understanding, and Dr. Gray, maybe you can inform us, that in some of the latest meetings you’ve been learning that immunotherapy along with chemotherapy can make a difference for people with small cell lung cancer, is that correct? 

Dr. Gray:                

Yes. Yes. That is absolutely correct. So, at our recent world congress on lung cancer meeting – now, this is our global international meeting for lung cancer where all the lung cancer experts get together now on a yearly basis. A lot of that has to do with that so much is changing that we now need to meet yearly. We used to meet biyearly.

One of the key presentations there that was in the presidential symposium seat or that’s the big session there was looking at combining chemotherapy with immunotherapy versus giving chemotherapy alone. And when they looked at this in patients with newly diagnosed, what we consider extensive stage or most people refer – may refer to it as stage four small cell lung cancer, that those patients derived a bigger benefit if we did the combination therapy. So, we’re talking about going from two IV infusions now to three IV infusions. So, you do add an hour, but there’s significant benefits that we all feel is also clinically beneficial for these patients.

If you happen to have small cell lung cancer and you are on chemotherapy there is also data that following your chemotherapy that utilizing immunotherapy in the subsequent line can also be helpful. So, these data are showing us consistently that immunotherapy is certainly effective in small cell lung cancer. And thank you for raising that point and that distinction. 

Andrew Schorr:   

Okay. So, Dr. Rosenberg, I’m gonna bounce this off of you as a cancer specialist. Not particularly about radiation but let me see if I get it right because we’re talking about immunotherapy.

When I developed cancer – and I’ve actually developed two blood cancers. So, I’m living with it. But whatever the cancer is, our bodies let us down, right? Our immune system has let us down and we’re starting to create aberrant cells, right? And they can develop masses like Ed had and they can spread. There’s a certain biology that the other doctors were talking about that they try to target. But with immunotherapy, that’s trying to leverage our immune system to do what it didn’t do right the first time, is that right? Is that the way you see immunotherapy? 

Dr. Rosenberg:    

Yes. Very much so. And one of the things that can define cancer is its ability to evade the immune system. In terms of our normal body, the way our immune system is set up is set up to go around our body and take care of any precancerous cells and try to destroy them. And unfortunately, what cancer does it has molecular mechanisms that try and basically get around these things. And so, the immunotherapy drugs that are out there help release the break in terms of the immune system to go back and attack these cancer cells.

And in terms of the interaction with radiation, because I am a radiation oncologist and I tend to bring it back there, is that what radiation can help do in that setting is actually destroy some of the cancer cells and kind of release what we call antigens into the blood stream or the nearby tissues to hopefully help the immune system better recognize the cancer. And when you take the break off the immune system and then allow the immune system to hopefully better recognize the cancer cells, these things all work together moving forward.

And so, I think there’s – only as we move forward, we see more interactions with radiation and the immune system and even these targeted therapies. I know that we went over – Dr. Boyle and Dr. Gray talked about how – these new targeted therapies that are out there. But even from a radiation point of view, we’re now really pursuing radiogenomics where we’re actually using some of these genetic signatures actually to determine how cancers respond to radiation treatment. And we’re actually sculpting our radiation to actually target certain areas of tumors to higher doses or lower doses based on some of these molecular mechanisms.

And it’s a really exciting time. And Moffitt particularly is really pioneering both of these areas to kinda push the boundaries in science right now.

Andrew Schorr:   

Well, good for you.

And I think, Ed, in listening, with this new age of cancer care it really argues wherever possible for people to get a second opinion at a major center like Moffitt where this brain power and leading edge of research can be brought to bear, wouldn’t you agree?

Edward Cutler:     

Oh, absolutely. No question about it.

I do have a question for Dr. Boyle. And that’s going back to the wheel of the mutations. Go back to 2013 when I was diagnosed, were all of those mutations tested when I had my biopsy or has the state of the art evolved such that now they do test for all of them? Or are there still some that they don’t test for until a certain event occurs?

Dr. Boyle:               

Right. So, there is still some disparity about where you go for your care and how many genes are tested. Certainly, Foundation One has a very large panel of genes. And I believe that was available in 2013. At Moffitt in this past year we validated a 170 gene panel that tested both the DNA and the RNA at the same time so that we can detect fusions like ROS1 and ALK at the same time as we’re detecting EGFR, KRAS, BRAF. All things on the wheel.

And so, I mean that only became available this year. In the past it was more piecemeal. And so, there were certain things that could be tested early on and possibly more things tested later. More and more we’re doing more comprehensive testing early on at diagnosis so that we know more at the beginning.

Andrew Schorr:   

I think there’s a point to underscore here is the field is evolving. The other day, Dr. Gray, we did a program that included someone you know from Harvard, Dr. Siegrist. And her advice, and I think you’d echo it, is wherever our audience gets care you wanna get a broad panel testing. And as we’re hearing from Dr. Boyle, the panel’s increasing, but the downside – and I know patients like this, for instance, with one of those more rare driver genes, ROS1, where they were tested sequentially and given, as you said, the wrong therapy for a while until they finally got around to doing the right tests and knew what was going on and did what’s right for them.

Dr. Gray:                

Yeah.

Andrew Schorr:   

So, I think for our audience, wherever you get care, and certainly it happens at Moffitt, you want a broad panel and as Ed was getting at is that panel is expanding.

Dr. Gray:                

Yes.

Andrew Schorr:   

What’s going on for you, and I think what you all say, and personalized medicine is, the right treatment for the right patient at the right time.

Dr. Gray:                

At the right time. Yeah.

Andrew Schorr:   

Okay?

Dr. Gray:                

Exactly.

Andrew Schorr:   

Okay. Let’s go to the role. We have another slide that describes the role. Really the team medicine approach, if you will. And let’s take a look at that.

So, okay. So, Ed was referred to Moffitt. Came there for a second opinion. And so, let’s see how it goes. So, Ed was the first place you went was to an oncologist. Was that first stop for you?

Edward Cutler:     

That’s correct.

Andrew Schorr:   

Oh, okay.

Edward Cutler:     

I went to a GI oncologist.

Andrew Schorr:   

A GI oncologist? But then it was discovered that it was really coming from your chest. And there was testing done. So, Dr. Rosenberg, let’s let you lead it. So, here I see radiation oncologist, medical oncologist, way down at the bottom we have molecular pathologist, like we have Dr. Boyle. How does all this work together?

Dr. Rosenberg:    

I think you’re gonna hear this theme over and over again, but it’s really a team with all of us. Especially say we meet to go over patients in a weekly tumor board which includes both our medical oncologists, radiation oncologists, surgeons, our pathology colleagues, our radiologists. It’s really all of us together. And so, as we gather information from a new patient, we’re trying to really determine what their stage is. Usually first of all based on imaging and then trying to establish a diagnosis through the tissues that we’ve gotten.

And once we kinda have that information we can meet as a team and kinda come up with a comprehensive treatment plan. And that includes gathering not only the tissue information, but the molecular information that Dr. Boyle really helps us put together there. And then after we have all that information gathered then we can kinda go down these different paths depending on what stage the patient has, what their molecular drivers are, and what sort of clinical trials and opportunities we have available for them that fits them in a very personalized way which really goes back to that personalized medicine that you were talking about there.

Andrew Schorr:   

Dr. Gray, any comments from you about this wheel? 

Dr. Gray:                

No, I completely agree with what Dr. Rosenberg summarized. I think we’re at – we’re a big referral center at Moffitt Cancer Center. And many times patients may come in with a biopsy. And I wanted to just touch base with what was mentioned before about getting enough tissue. When you do do biopsies to work up for the lung cancer that is very important. And I think this wheel here and this summary here helps to highlight that. That we really want to get down to the point where we’re really collaborating with the molecular pathologist looking at your biopsy within the lab. And perhaps getting that circulating tumor DNA analysis in a blood also to make this decision.

And I fully concur that this is a team approach. We really need the pathologist to let us know what’s going on. We really need to sit down as a team and make sure that we all come up with the right decision for the patient. And that’s certainly one of the benefits of going to a place like – you mentioned Harvard and coming to the Moffitt Cancer Center certainly also.

Andrew Schorr:   

Right. So, Dr. Boyle, so there are people listening who maybe have had a biopsy somewhere else. Maybe at the community level. And here, you’ve got this big lab and you have other groups that you work with with huge analyzers and pathologists and all that that you work with. Somebody says, “Well, if I come to Moffitt” – oh, any other major cancer center, sometimes the request is made to have another biopsy or other tests. Why is that important today? Because do you have sometimes where maybe the initial analysis wasn’t as correct as it could be?

Dr. Boyle:               

Right. It’s kinda like the bane of our existence. People like to say the tissue is an issue.

Andrew Schorr:   

Nice. 

Dr. Boyle:               

And it goes along with the “if you don’t have an adequate specimen you can only get so much information out of it.” The blood testing has really helped alleviate some of that pain, but when a procedure’s going to get a small bit of tissue from the lung, it can be less than 100 cells. And we’re trying to do the best we can to learn about 100 tumor cells. So, that’s why the biopsy is so important. And I was thinking maybe we can go around the wheel. We are missing the surgeon in here, but I love this appearance and how you can go around and around and around.

Andrew Schorr:   

Right. 

Dr. Boyle:               

But the patient usually first comes in and sees their oncologist and then a biopsy can be taken, and it goes to the anatomic pathologist and they determine is it adenocarcinoma or squamous cell cancer, small cell or some other primary cancer.

And then the specimen get to genetic testing. They go to the lab and that’s where we come in. We’re looking, “What’s the tumor cellularity? Is it enough for us to even test? Can we test with the targeted small panel if it’s not enough for big next generation sequencing panel?” And we do the sequencing on our big fancy machines, but we get the results. And it really requires pretty intensive interpretation to understands the results and make sure that we’re reporting out accurate results.

Andrew Schorr:   

Yeah. I wanted you to speak to that. There’s an art to – there’s an art to medicine.

Dr. Boyle:               

Well, yes. 

Dr. Gray:                

Yes.

Andrew Schorr:   

Of course. But there’s an art to pathology. And so, you wanna give accurate recommendations of what are we dealing with to the medical team, the rest of the medical team, and that has an art to it, right? And you’re a subspecialist in that area.

Dr. Boyle:               

Okay. Right. And we don’t want to overwhelm oncologists with too much information either. So, we’re very receptive to feedback about what’s most important for actually taking care of your patients that you’re seeing. And the resistance mutations have become very important. We used to only check for one part of the ALK gene and we got feedback from the oncologist that that wasn’t good enough. They need to look at all of the ALK gene for resistance mutations. So, back and forth.

And then we also have the help of the personalized medicine group here at Moffitt. And that’s wonderful. They have [inaudible] [00:47:19]. So, they know about drug side effects. They know how to work with insurance companies. They know how to answer questions about what’s the functional effects of genetic changes. So, when we send out a report, it goes straight to the oncologist, but it also goes to the personalized medicine group for a more in-depth look. And maybe some help identifying clinical trials that the patient might be newly eligible for based on the genetic findings.

And the radiation oncologists have become more involved too. As Stephen was talking about how the genetics can play a role in the care in terms of the radiation. There’s more and more clinical trials that are getting involved in together to better understand what’s the best therapy.

Andrew Schorr:   

So, Dr. Rosenberg, what I’m getting from this is a patient might see Dr. Gray or see you or maybe a surgeon with earlier stage lung cancer as well, but that there’s this whole group – Dr. Boyle, but she rattled off a few other groups as well that are all behind the scenes. And you guys are talking about me, the patient, right?

Dr. Boyle:               

Oh, yeah.

Dr. Rosenberg:    

Yeah. Absolutely. I think that we are really in communication with each other on a pretty regular basis as a team. And I think that’s what really leads to this personalized care for the best outcome for the patient is really being very communicative about – between Dr. Gray and between Dr. Boyle, between the surgeons that we work with and just everybody really working together to try and make the best decision we can for each patient.

And gathering all the right information upfront. I think that’s really the key is making sure we have all the right information we need, whether it’s molecular or imaging, before we go down a certain path, so we don’t go down the wrong path for any particular patient. And yeah, I think as we kind of put that information together we can help really personalize each person’s care that way. And from a radiation point of view we’re using both the imaging information that we’re getting and the molecular information to help make radiation decisions.

And at Moffitt, we’re really trying to push those boundaries from imaging as well. And we talk about personalized care from these molecular changes, but Moffitt, this room will be opening up our MRI-guided radiation treatment unit which is the first in the country. There’s only a handful of places that are doing MRI-based radiation treatment. And that’s really another form of personalized care by seeing somebody’s anatomy up close and in a very particular way and designing the radiation based on individual anatomy. And so, with that better imaging we’re able to do that. So, there’s a lot of ways to personalize care for patients moving forward.

Andrew Schorr:   

So, Dr. Gray, I wanna talk about the spread of cancer. So, Ed talked about how he had this on his liver. But you figured out – you all figured out it came from his lung?

Dr. Gray:                

His lung. Yes.

Andrew Schorr:   

Lung cancer can spread. Cancer can spread generally. But here we have people with metastatic cancer who are living longer with some of these approaches. 

Dr. Gray:                

Yes.

Andrew Schorr:   

Radiation, immunotherapy.

Dr. Gray:                

Therapy.

Andrew Schorr:   

Targeted therapy. 

Dr. Gray:                

Different therapies.

Andrew Schorr:   

So, when you tell somebody, “Mr. Jones, yes, you’re right. Imaging, we see your cancer spread.” That’s not the end of the story.

Dr. Gray:                

Absolutely not. No. So, what we also look at are these genetic findings, the pathology findings, the markers for the immunotherapy. But at the end of the day what your goal is is to extend life and to add quality of life to patients. And so, as we look at this information, we want to make sure that we’re making the right decisions. And this is the goal ultimately of personalized medicine.

Yes, your cancer may have spread, but we can give you treatments that are gonna knock down the cancer, get it to shrink down, and to a point that sometimes may become undetectable on the scans. We do think that there’s cells still circulating there, but we could still continue to follow you and keep track of the cancer and make sure that you’re – we’re helping you to manage this properly.

Andrew Schorr:   

Okay. So, I wanna remind our audience, send in your questions. This is an ask the expert question. We have an expert patient who’s lived it. And I know Ed, you spend time talking to other patients and family members. We have Dr. Boyle and we got her out of her lab there.

Dr. Boyle:               

Yeah.

Andrew Schorr:   

You might not see her in the exam room, but she plays a key role. We have Dr. Rosenberg who’s even travelling and joining us. And Dr. Gray. So, if you have a question send it to lung@patientpower.info.

And I wanna tackle a question. Here’s one we got from Gretta, “What percentage of blood biopsies are accurate?” She said, “I had one done and it showed I no longer had the BRAF mutation, but subsequent tissue biopsy showed I did still have it. So, how reliable are the liquid biopsies?” And I think you, Dr. Boyle, mentioned that a little bit.

Dr. Boyle:                                 

Right.

Andrew Schorr:   

So, this is a new area of pathology. In this area, how much can you rely on it?

Dr. Boyle:               

Right. So, the positive results we are finding when you’re testing with a reputable company they are – can be very reliable. Just as reliable as the tissue testing for the positive results. And there are some advantages even. Because in the body you might have a tumor on the lung that’s a little bit different from the tumor that spread to the liver, whereas the blood is a big mixing bowl. And if you have some DNA sloughing off the two different tumors, that DNA is mixing in the blood. So, you’re getting a more comprehensive look at the mutations in the blood.

One big, big disadvantage that’s represented in this question is when you get a negative result. When you get a negative result like she got for her BRAF in the blood, it’s really a non-informative result as opposed to a negative result that you can hang your hat on. Because you don’t really know how much cell-free DNA is actually sloughing off the tumor and circulating in the blood. And so, if it’s not in the blood, you might get a negative result when really, it’s still BRAF positive in the tumor as she found when she had this tissue tested again.

Dr. Gray:                

Positive.

Andrew Schorr:   

But this is evolving, right? I mean we couldn’t even talk about liquid biopsies not too long ago. So, the sophistication and the sort of getting down almost Nano – the Nano-level, you’re working on it, right?

Dr. Boyle:               

And that’s what Jhanelle and I have talked about this so much with algorithms for how to really understand the results and use the results.

Dr. Gray:                

Yes.

Dr. Boyle:               

And this is something that – at Moffitt we know well about the negative results being more like non-informative results with the blood. And we find them very helpful when we interpret them appropriately. 

Andrew Schorr:   

Okay. Well, there we go to the art and the sophistication of the tools that continue to develop. So, a lot of computing power folks that go into this. And then the wisdom of folks like Dr. Boyle.

All right. Here’s a question we got from Greg. I think this is for you, Dr. Gray. “What is happening in research for those of us who do not have target therapy gene mutations and also have a low tumor burden. Is chemotherapy the only option?” 

Dr. Gray:                

No. So, if you look at the studies that have occurred so far, looked across the patients that have a low tumor burden or have a negative PD-L1, or have no actionable or driver mutations, we still know that chemotherapy plus immunotherapy’s the way to go. We’re also doing a lot of research in that setting is that once those or if those stop working for you, what are gonna be the next steps? And that I think is certainly an area of need. One of the things that we’re looking at is combination immunotherapy strategies. That perhaps giving you one immunotherapy therapeutic agent was not enough and that you perhaps need two.

I think that chemotherapy is still very important. And doing combination strategies down the line with some of these novel agents. When we look at some of the – a lot of the trials, even the ones where you give chemotherapy with immunotherapy, if you look at the data, most of the benefit upfront, for now at least, appears from the actual chemotherapy. So, chemotherapy is very good at reducing disease bulk. But the immunotherapy can then come in and activate – help to activate your immune system. And the ultimate goal of immunotherapy is to create immune memory, okay?

Almost along the lines of a vaccine. You get your flu vaccine once a year because it mutates. You get your hepatitis vaccine. You’re not getting it every year. You only get it for a sequence. And the purpose there is that your immune system should be able to sustain on your own. And we wanna do that for patients upfront. That would be the ideal. But we also recognize that we just – this is very new, and we don’t know enough.

So, I think expanding more in combination immunotherapy strategies, looking at novel agents, looking at where chemotherapy’s target also and probably repurposing those drugs a little bit so that we can actually hit the target even better than regular systemic chemotherapy and reducing toxicities. There is a plethora of research going on within all avenues.

So, I think the key thing there is that if you have something and it’s not working for you, come to a center of excellence like Moffitt Cancer Center and sit down and talk to us and we can let you know. And exactly to your point. We talk to physicians all across the globe. Work very closely with Dr. Siegrist at Harvard. We share patients. Share data constantly. Even if we may not have something for you here at Moffitt, there may be somewhere else in the United States that we can send you also.

So, I would not – I don’t think – the key thing there is that giving up should not be the first option by any means.

Andrew Schorr:   

Amen. I just wanna drop back for a second and make sure everybody understands this whole world Dr. Rosenberg talked about a little bit. So, the immune system let us down. And Dr. Boyle a while ago used this term checkpoint.

Dr. Gray:                

Yes.

Andrew Schorr:   

So, Dr. Graham let you be the professor here. See if I get a good grade. The cancer cell has this kind of protective world around it where medicines traditionally maybe don’t kill it. 

Dr. Gray:                

Yes. Correct. Correct. 

Andrew Schorr:   

Right? Okay. So, what the immunotherapies are doing, maybe more than one, is to knock down that barrier.

Dr. Gray:                

Yes.

Andrew Schorr:   

So, that whether it’s with radiation like Dr. Rosenberg talked about with these immunotherapies where your immune system can do its job in killing the cancer cells, the abnormal cells.

Dr. Gray:                

Yes.

Andrew Schorr:   

And you also eluded to something else where the immunotherapy can continue to do this surveillance wherever the cancer may be. Whether it’s spread to Ed’s liver, whether it’s gone to somebody’s bone.

Dr. Gray:                

Yes.

Andrew Schorr:   

Wherever it is it says, “Oh, now I see you.”

Dr. Gray:                

Yes. 

Andrew Schorr:   

“And guess what? Bad news. I’m gonna kill you.” Right? 

Dr. Gray:                

Kill you. Correct. 100% right. So, one of the ways to think about this is that the immunotherapies, if you see the commercials out there, for example, for Opdivo or Keytruda, they actually do not kill the cancer cells. So, this is very different than chemotherapy. Traditional chemotherapy we’re very used to goes in, actually kills the cancer cells. Exactly. The immunotherapies are unmasking the tumor to the immune system allowing the immune system to now recognize the cancer cell as foreign and then attacking the cancer cells. And exactly, your immune system should then sustain on its own. And that is the ultimate goal of immunotherapy.

Andrew Schorr:   

And Ed, that’s what you’ve been living with, right? You said earlier you’re stable. So, you’re taking immunotherapy and it’s kinda knocking it back, right?

Edward Cutler:     

Yes, it is. To what Dr. Gray said with respect to, I guess, first line of treatment with the combination of chemo and immunotherapy, what is the standard now with the combination? Is it Alimta, Avastin and then Keytruda or Opdivo?

Dr. Gray:                

Yeah. So, right now as of 2018 what is approved by the FDA – I’m just going back a little bit. Remember there’s two main types of lung cancer. There’s small cell lung cancer, there’s non-small cell. There’s two main types within non-small cell of a non-squamous type of lung cancer and then a squamous cell type lung cancer. And to Ed’s point, he’s completely right, your chemotherapy that we choose for you depends on your type of lung cancer. And I think that’s what you’re alluding to in the question.

Edward Cutler:     

Yeah. Yeah. 

Dr. Gray:                

So, there are data that has shown for non-squamous, non-small cell lung cancer if you combine Carboplatin plus Pemetrexed plus Pembrolizumab together, that is the FDA-approved regimen for first-line – for that type of non-small cell lung cancer.

Now, if you have non-small cell lung cancer and the subtype is squamous cell, the drugs that are approved right now are Carboplatin, Paclitaxel, plus Pembrolizumab. Or you can substitute that Paclitaxel for something called Nab-Paclitaxel or Abraxane. Paclitaxel can cause some infusion reactions in patients. And so, the Nab-Paclitaxel is formulated to minimize that infusion reaction. So, there’s some flexibility there, but they’re still in the same class there.

So, and then if you have the small cell lung cancer actually the regimen that is approved there is a platinum – so cisplatin (Platinol) or carboplatin (Paraplatin) plus Etoposide plus etesolismab. So, it’s really even within that spectrum these are all ways of personalizing medicine for patients. And really having that level of information from the pathology and the biopsy side so that we can make the best decision for the patients. 

Andrew Schorr:   

Okay.

Dr. Gray:                

And then when that data comes in is having that expertise about which one is gonna be the right for which patient.

Andrew Schorr:   

Right. But there’s one other aspect I wanna put on. So, for patients, whether you go to Moffitt or another major center, rather than some of those names she mentioned, there may be a clinical trial where it has a number.

Dr. Gray:                

Yes.

Andrew Schorr:   

And it says, “We’re gonna give you X, Y, Z, 1, 2, 3, 4. That’s what we recommend,” which hasn’t been approved, but they believe may offer a better option for you.

Dr. Gray:                

Yes.

Andrew Schorr:   

Did I get it right?

Dr. Gray:                

Yes. Correct. And so, we call them license plates, right? License plate numbers. And so, when the drug first comes out of drug development, it kind of gets this license plate number and Nivolumab, Pembrolizumab, all of them came out with these license plate numbers as we call them. And then you just – as they move forward, and they show promise that they then develop a more formalized name – nomenclature for the naming. But to your point, it is very important to also look at clinical trials within that setting. That’s how we make these strides. That’s how we make these improvements.

We participated in a very first trial with Nivolumab here at the cancer center and I still have a patient that is alive six years out. His daughter was five when I met him. She’s 11 now. They sent him to hospice on the outside and I said, “You know what? We’re gonna try this medication.” And he has not received the immunotherapy in four years. And this is a perfect example where his immune system was able to work, get the tumor down, and now it’s sustained on its own off therapy. And if he didn’t come to Moffitt, he would’ve just been sent to hospice.

Andrew Schorr:   

Okay.

Dr. Gray:                

So, this is where exploring – making sure that you explore all of your options is very, very important. What I always recommend, you know what? Can you get treated locally? 100%. But at least go in for that consultation. Make sure that there’s not something newer, more novel, something that we think may be a little bit better. Clinical trials is always a way to explore things. At the end of the day the standard of care FDA-approved therapies are always there, and we can always give them to you whenever. You may have this option for this trial. And I think my patient got one of the last slots on the trial nationally. And I think… 

Andrew Schorr:   

…wow. What a story. I just wanna recap a couple things for our audience, okay? So, you got it now about personalized medicine and getting what’s right for you, whether it’s one of these targeted therapies in this growing list of genes that Dr. Boyle has talked about. And drug companies and government working to development things that match up with that. Immunotherapy, maybe more than one. Some that have a commercial name and some that have a license plate like Dr. Gray just described.

And then this whole idea of radiation oncology where Dr. Rosenberg and his colleagues are finding out how does all this work together? How can radiation actually trigger something in a cancer cell that then also helps it say to the cancer drug, “Hi, I’m here.” Boom. They get hit by a cruise missile, right? So, that’s what they’re working on.

All right. We’ve got a bunch of questions. Remember, lung@patientpower.info. This one came in from Leo. And Leo says, “Any new research or treatment regarding patients with the TP53 mutation?” So, first of all, Dr. Boyle, what is TP53? 

Dr. Boyle:               

Oh, goodness. I don’t off the top of my head know how that spells out, but it is a tumor suppressor protein. And it’s a gene which we find frequently mutated in all cancer types. And it often causes a worse prognosis. And there are many researchers trying to see if there are better drugs to target therapies. And lung cancer, the clinical trials are pretty early. The highest you get is phase one and two. So, there has not been a lot of success yet. In leukemia I think there’s more phase two trials.

We have an excellent researcher here, Elsa Flores, who is looking at animal models in vivo studies to try to understand more. Now, one thing sort of interesting about TP53 is that if you have lung cancer with TP53 and a KRAS mutation, that mutation is gonna be more likely to respond to immunotherapy.

Dr. Gray:                

KRAS mutation. 

Dr. Boyle:               

There’s a really nice paper out by John Heymack about this if there’s also an STK11 mutation. So, then it’s a lower likelihood of response to immunotherapy.

Dr. Boyle:               

So, with more and more research we’re lending some of the nuances of these and we’re hopeful that there’s going to be more that can be done with the TP53 mutations in the future.

Andrew Schorr:   

Okay. So, Dr. Gray. So, you were nodding your head while she explained that? 

Dr. Gray:                

Yeah. Yeah.

Andrew Schorr:   

So, in other words, you’re looking at not just one gene being the bad guy, but this constellation in a given patient.

Dr. Gray:                

Right.

Andrew Schorr:   

And does that tell you something that you could do in a more refined way for them?

Dr. Gray:                

Right. I think this is we’re coming into a center where we have this level of expertise and we’re sharing data across the different centers. But exactly what Dr. Boyle noted is that when we look at these genomic reports, right, you’re getting a lot of information coming out back at the medical oncologist. And knowing how to fully understand and interpret that data so you can make the best decisions for the patient is very helpful.

So, if we see a KRAS mutation, the P53, without an STK11 mutation, certainly that will move immunotherapy up on for the armamentarium for the patient. Now, this is a little bit in experimental mode, but we’ve seen similar data here at Moffitt. And it’s really starting to pick up traction across different cancer centers and lung cancer experts.

Around the specific question of the P53 mutation, we do have a compound that we’re looking at here in collaboration with AstraZeneca. It came from a trial that I had written and am working on that came from work derived here from Moffitt Cancer Center. It’s called AZD1775. But it basically what it is is it’s looking at inhibiting the cell cycle. I’m gonna take us back to biology a little bit. And cells, how they replicate, basically they have to go through mitosis, right? You have to replicate your DNA and then split off and divide.

And so, what the P53 does is it’s almost – as Dr. Boyle mentioned, it’s a tumor suppressor. What does that mean? It actually puts a stopgap, an intentional stopgap when cells go to replicate. And it makes the cell stop and check and say, “Do I have any mutations? Should I move forward or not?” What cancer cells do is they’ve lost – they mutate the P53. So, they don’t get that stop in place. They just keep replicating. Even though technically these are abnormal cells, they’re damaged cells and they shouldn’t replicate themselves.

So, what that drug does is it intentionally incorporates – if you have that P53 mutation your cells are not stopping when they’re replicating abnormally. This AZD1775 helps to add that stop so the cells can check themselves and say, “Hey, you know what? We’re really not replicating ourselves properly. We should actually go towards cell death and not cell survival and replication.” So, there are definitely trials that are looking at the P53, to Dr. Boyle’s point, including one that was derived here. And as Ed mentioned, something that you can only find here at Moffitt. And we hope to have that data out maybe later this year or early next year.

Andrew Schorr:   

Okay. Stay tuned.

Here’s a question we got from Jim. “How does immunotherapy work in EGFR mutations after targeted therapies no longer work?” Do you wanna comment?

Dr. Gray:                

Yeah. Yeah. So, that’s a great question. So, one of the key things as I mentioned before is if you find a mutation such as the EGFR mutation you go down the realm of a targeted therapy. So, say to treat patients with a targeted therapy’s very, very important.

I wanna take this opportunity to say that you should not combine an EGFR inhibitor with an anti-PD1 with an immunotherapy. It significantly raises patient’s toxicity. So, if a physician ever – if that ever comes up, at least for right now, the answer, you should decline that, and no one should be offering that to you. Exactly.

So, I agree that the best way to incorporate them right now is through a sequential approach. So, you start with the EGFR inhibitor. And there’s four of them actually FDA-approved right now. So, you may get sequenced from one EGFR inhibitor to the next. What people are looking at right now is should we go straight to immunotherapy, should we go straight to chemotherapy, or should we go straight to a combination strategy of chemotherapy and immunotherapy?

I think based on the data for right now, most of us as long as we think that it’s safe will go to a combination of chemotherapy plus the immunotherapy based on the data. This is gonna be looked at more in detail to finally answer this question. It also depends on the wishes of the patients too. So, if you think that you cannot – if a patient cannot tolerate, for example, immunotherapy combination with chemotherapy, we may start with one or the other and then move on. But definitely I agree that the sequencing is gonna be the best way to do that.

Andrew Schorr:   

Okay. Let’s talk about the toxicity for a minute. So, Ed, you had – earlier you had some treatment that was pretty tough to take, right?

Edward Cutler:     

Yes. Yes, it was. The only major side effect that impacted me was colitis. But it was major. It was really, really major.

Andrew Schorr:   

And you had to change? You changed?

Edward Cutler:     

And when I read the protocol, yes, that was one of the potential side effects.

Dr. Gray:                

Right.

Edward Cutler:     

But that’s all it was was a potential side effect. I took my chance with it. I’d never had colitis before and then it hit me. And I’m still kind of dealing with that to some extent. Nowhere near what I dealt with three years ago.

Andrew Schorr:   

Okay. And your treatment was changed?

Edward Cutler:     

And my treatment was changed. Yes.

Andrew Schorr:   

Okay.

Edward Cutler:     

And that was a combination – a two drug combination trial.

Andrew Schorr:   

Yeah.

Edward Cutler:     

A phase one trial.

Andrew Schorr:   

Here’s a question we got in from Wendy. So, it’s a little technical, but she says, “I’m currently keeping my stage four non-small cell adenocarcinoma at bay with monthly maintenance infusions of Pemetrexed.” Did I get that?

Dr. Gray:                

Yes. Absolutely.

Andrew Schorr:   

“I was diagnosed in August of 2015. Nothing visible on PET scans, but the chemo’s been prescribed to keep the cancer reappearing.” And her concern is the long-term damage, she wonders, of getting chemo infusions over a long time. She says, “What could be the downside of chemo over a long term?” Dr. Gray?

Dr. Gray:                

Yeah. So, one of the things that we – well, congratulations. I’m glad that you’re doing so well. That’s really inspiring to hear. And I think that speaks to the fact that there are patients and cancers out there that respond to chemotherapy and I think that we should still keep that in mind.

The long-term side effects that we generally worry about with chemotherapy are how they affect your blood counts. And by blood counts, I’m talking about your bone marrow. So, your red blood cell counts. So, your hemoglobin and your hematocrit. Your white blood cell counts. Your leukocytes. Your neutrophils. Things that help you fight bacterial infections, viruses. And then your platelet counts. These really help with your clotting. So, if you cut yourself.

Pemetrexed, in particular one of the things that we’ve noted when you keep receiving this treatment in particular over time is that the anemia seems – can sometimes be a rate limiting step. So, I’d definitely keep an eye on your hemoglobin and hematocrit.

But I’ve had patients on these maintenance therapy agents for many years. A lot of times what I will do to lessen the burden for the patients. Normally the drug is infused as an IV infusion over ten minutes every three weeks. I will go to once every four weeks so that you’re only coming in once a month for a treatment to add more to quality of life. And then I’ll start increasing the frequency of the scans to less frequent. So, maybe quarterly you’ll get a scan instead of every six weeks. So, hopefully all these scans can help lessen the burden of the infusion and also help to improve quality of life at the end of the day. But I would certainly be careful of watching the blood counts within the study.

Oh, I think you’re on – are you on mute?

Andrew Schorr:   

Yeah. I’ve got it. Sorry.

Dr. Gray:                

Yeah? Sorry. 

Andrew Schorr:   

Dr. Rosenberg, related to toxicity you referred earlier about MRI-guided radiation. What are you doing in the radiation oncology field to get at the cancer, but not effect either healthy tissue – and also lower the side effects that can go with radiation. People that fatigue and other things that go along with it. And all of you have been talking about higher quality of life where you might be living with lung cancer.

Dr. Rosenberg:    

Yes. Yeah. It’s a great question. And I think how we’ve approached this in radiation oncology is actually by shortening our treatment courses. And as our technology has improved it will also give us very small volumes of irradiation with high doses to destroy cancer cells, but also sparing normal tissues. And as patients are living longer with lung cancer, we kinda have to say sometimes they’re responding well to chemotherapy or immunotherapy or targeted therapy, but one area is starting to grow, we use this targeted therapy called stereotactic body radiotherapy, SBRT. So, [inaudible] go after these important small areas that might be not responding appropriately or may even be resistant.

But these are targeted areas that we’re irradiating that are very small in volume. That’s really helped us limit toxicity, but to normal tissues going forward. And with the new MRI-guided treatment program, which is where my focus is gonna be, is that by having the MRI help us guide our treatment in real time, we can make our volumes even smaller. And by shrinking our volumes and targeting tumors more appropriately we can hopefully spare normal tissues and actually decrease side effects long-term for patients.

And so, again working with our medical oncology colleagues is that if there’s an area of resistance that pops up, an area that we can very precisely target, we’re still sparing a lot of the normal tissues in your body.

Andrew Schorr:   

Okay. Precision radiation oncology?

Dr. Gray:                

Yeah. Yes.

Andrew Schorr:   

Okay. 

Dr. Gray:                

And we do that also. And if I may add that if there’s somebody who’s on a treatment benefiting and they just have one area that’s kinda this rogue tumor that breaks through and becomes resistant, that definitely looping in the radiation oncologist, working with Dr. Rosenberg and his team, and targeting that specific area can be very effective for patients.

Andrew Schorr:   

Okay.

Dr. Gray:                

Before you switch therapy.

Andrew Schorr:   

Here’s another aspect of immunotherapy. So, we talked about these PD1, PD-L1 drugs, checkpoint inhibitors. So, another area that’s particularly happening in the leukemia’s that I know well is what’s known as CAR t-cell therapy, chimeric antigen receptor t-cell therapy. Where if I get it right, correct me if I’m wrong, you can sort of engineer t-cells to become sort of a targeted therapy.

Dr. Gray:                

Yes.

Andrew Schorr:   

All right. So, what about this in lung cancer, Dr. Gray?

Dr. Gray:                

Yeah. So, it’s a great question. So, one of the areas – this has really taken off in the hematologic malignancies are these CAR-T therapies. The hematologic malignancies are very well-defined by specific markers on the cells that are uniformly found across different types. So, lymphomas, leukemias. In the solid tumor realm, it’s been a little bit more of a challenge with finding where to specifically target. And also, to target the cells without adding significant toxicity to the patients.

So, we do have what’s called an ICE-T therapy here. It’s the immune and cellular therapy. It has medical oncologists on that team, both hematologists and hematologists. And they’re working together to help bring what we’ve learned from the hematology world over to the solid tumor realm. So, it’s new. I don’t think it’s yet ready for FDA-approval, but absolutely a very exciting, exciting field. Again, the purpose of these is to create these long-lasting responses with a personalized medicine approach.

Andrew Schorr:   

Yeah. I wanna thank Gordon for that question. I think we hear about – you mentioned TV commercials, or we see an article in the paper.

Dr. Gray:                

Yeah. Great question.

Andrew Schorr:   

And we say, “Oh, how does that apply to me?” Or, “Should we get on a plane and go somewhere because they’re trying this out?” It’s really tough. So, Dr. Boyle, you see this changing field.

Dr. Boyle:               

Okay.

Andrew Schorr:   

What would you say knowing what you know in going on and identifying new genes, if you had a family member – and I hope you haven’t, but if you had a family member diagnosed with one of these conditions, what advice would you give them? Because you’re on the inside. Or maybe you have friends or neighbors that call you up, “Oh, my God. We got this diagnosis. What should we do?” What’s sort of an operating system for patients and families today? What would you say?

Dr. Boyle:               

Right. Well, one thing I want to ask always, what Jhanelle was talking about earlier with the clinical trials, if you are getting the optimal standard of care plus whatever new innovative potential therapy might be available with those trials. And there actually is a better outcome with the participation in the clinical trials. They’re very carefully designed.

So, I would want a family member or a patient, it is the same, to get as much information as possible. And like Jhanelle said, it’s fine to get your care locally, but to get a second opinion at the most advanced center available to you for a second opinion. Get more information. See what’s available. Consider clinical trials. Sometimes just following the basics. Like if you have an EGFR mutation to get an EGFR inhibitor therapy and not be wanting say immunotherapy just because it’s the newest thing. That’s what I’d be thinking about. And getting the rapid care can be important too.

One thing I wanted to add onto what Jhanelle said earlier about the T-CAR conversation is that we also have a trial here with the tumor infiltrating lymphocyte. It’s not by definition a T-CAR trial, but it’s in lung cancer. And they’re basically taking lymphocytes out of tissue and growing them up in cell culture and reinfusing them into lung cancer patients in the hopes that the reinfused cells will attack the tumor. And I just think this is amazing progress that this being tried in lung cancer too.

Andrew Schorr:   

Here’s a point I wanted to make. So, I hope what all our viewers get – and I think we have some pretty savvy questions that have come in. The field is changing. And so, Dr. Gray, I’m sure when you went through your training there wasn’t always a lot to talk about with patients, right? 

Dr. Gray:                

Oh. No. That’s very true.

Andrew Schorr:   

And now we have people like Ed who are living longer, living pretty well. There are side effects we’ve talked about. Ed was talking about trying to limit that. So, the quality of life goes along with living well and living longer. But there’s a lot of progress being made, and you and your family have to be plugged into that. And yet, Dr. Boyle just referred to that. Don’t get excited about something just that you see on TV because it may not be right for your specific situation. And Dr. Gray was warning about that too. If you have EGFR, that’s not the time for immunotherapy, right?

Dr. Gray:                

Correct.

Andrew Schorr:   

Even though you saw the ad of people in town square. New hope for lung cancer. 

Dr. Boyle:               

On the highway. Yeah.

Dr. Gray:                

Yes.

Andrew Schorr:   

Yeah. So, you really have to – you really have to think about that. So, testing, broader panel, second opinion, team approach? 

Dr. Gray:                

Yes.

Andrew Schorr:   

We’ve got a wonderful team here.

Here’s a question that we got in. We just have time for a few more questions. But Helen asked this question, “Is there any research or anecdotal information on how much the drug Alimta adds to the efficacy of another immunotherapy Keytruda. Does it continue to be effective indefinitely or does it only work for a while?” Dr. Gray?

Dr. Gray:                

Yeah. So, there’s a recent study called the Keynote-189 study that combined Pemetrexed, Carboplatin, plus Pembrolizumab. So, Pembrolizumab is the immunotherapy. The Pemetrexed is the chemotherapeutic agent. And they treated those patients with the Pembrolizumab up to about two years.

The study was published, and it was found to be positive in the sense that it improved patient’s overall survival. So, how long were you gonna live? And also, what we consider your progression for your survival. How long did it take your cancer to actually progress to the point that we would need to switch your therapy? So, it was longer in that group than just giving the chemotherapy group.

You ask a very good question. These are the questions that we also, within the lung cancer field, are asking. How long do we really need to give these therapies for? Especially when you’re giving them in combination with immunotherapy when the goals of immunotherapy are to create long-term memory.

We have studies looking at giving immunotherapy for one year. We have studies continuing the immunotherapy indefinitely. And we have studies looking at giving the immunotherapy for two years. I think outside of the stage three – in the stage three setting, the clear data is that you give it for one year. Outside of that, I still think that it’s still a tossup. My suspicion is that you should at least probably go beyond one year if you can and see if you can’t get to the two-year mark. That’s where most of the data is at a minimum.

I actually have a patient now coming up on her two-year mark in February of this year on Pembrolizumab and I’ve started having those discussions with her and it’s an open discussion that, “This is what the data shows. What do you feel comfortable with?” And so, I think there needs to be a shared decision-making process within this realm also. And what the patient feels comfortable with and what the data helps to support. So, I think keep having those conversations, especially if you’re getting it combined with the immunotherapy. And hopefully there will be more to come definitively.

Just for a historical perspective, if you look back many decades ago when chemotherapy first came out, we used to give chemotherapy for a year. Then they did the trials where they actually looked at it at a year versus six months. The outcomes were the same with giving it over six months. And then they went from about six months versus about three months of therapy. And now went back a little bit, but added the maintenance in. And so, there’s definitely these trials will come, it’s just going to take time. The world of immunotherapy is very novel within the realm of lung cancer. And so, we have lots of growth to do.

But fantastic question. That’s probably one of the things that we sit and debate at our meetings very frequently.

Andrew Schorr:   

So, as we come near the end of our program, I wanted to get some final comments from our panelists. I’m gonna end with Ed because Ed, I want you to talk to other patients and family members.

But what I get from this is the field is pretty rapidly changing. Whether it’s in radiation and how that applies to other therapies. Whether it’s combination therapies, sequential therapies, duration of therapies we were just talking about with Dr. Boyle. It’s about identifying new genes or combinations of genes and trying to figure that out. So, what do you wanna say to a patient audience?

I’m gonna start with you, Dr. Rosenberg. So again, we have people all around the world and they or a family member has been given what’s a pretty terrifying diagnosis.

 Dr. Rosenberg:    

And it’s a scary time as they’re facing this. And actually, what I’m talking about here in Madison is actually putting together your medical and emotional teams as you’re basically facing this new diagnosis. And I think that’s the big thing is putting together a team and being someplace where you have the support and you feel comfortable. And also seeking out multiple experts to try to come up with the best plan you can moving forward.

And I think as Dr. Boyle, Dr. Gray, as the panels all alluded to, seeking that second opinion just to at least know what all your options are and are available to you is really important. Building your treatment team which includes so many different experts both that you’re gonna meet in person and behind the scenes. And I think that’s the real key aspect to this.

Andrew Schorr:   

Well, thank you for what you do. And this cool area you were talking about having radiation trigger a response in the cell that can make it more responsive to new medicines is really great. Good luck with all of that. Thank you.

Dr. Boyle, so you are a CSI detective. You are. You have like a magnifying glass.

Dr. Boyle:               

I love my job.

Andrew Schorr:   

Yeah. You have much more powerful tools than that. But you’re a sleuth. So, are you confident that this field is – will continue to expand to really unlock these secrets so you can say to these other team members, “Hey, I think this is what we’re dealing with and here’s a key pressure point to go beat that cancer.”

Dr. Boyle:               

Yes. Yes. I’m very optimistic. When we validated this 170 gene panel we did not even know if we would be reimbursed, but we did it anyway because we have so much optimism that it will have value and show value. And I really feel like understanding the cancer better. And it’s a key to better therapy. And my thinking is that patients should hold onto their hope throughout their whole experience and stand their ground. 

Andrew Schorr:   

Yes.

Dr. Boyle:               

Know what they want and don’t want and ask questions to their oncologist if they have questions. Because there’s a whole new world here and we’re all trying to figure it out together as a team. But we really appreciate the input from the patients as well. I think that’s helpful to helping all patients and future patients as well.

Andrew Schorr:   

Well, I wanna thank you for what you do behind the scenes as far as we patients and family members see you. But with your colleagues around the world continue to make these discoveries so that the therapies can be targeted or more broad. But whatever they are, know what we’re dealing with, so we get what’s right for you. Dr. Boyle, thank you for being with us too.

Dr. Gray. So, you have these partners here and we have patients and family members who you’re partners to. And as I alluded to earlier, in your own career you’ve seen a lot of change.

Dr. Gray:                

Yes.

Andrew Schorr:   

Is this a message of hope? And are you comfortable that more of us – even now we’re talking about small cell lung cancer where there’s progress being made that can extend life.

Dr. Gray:                

I’m very hopeful. I think that we have completely revolutionized how we treat patients – treat lung cancer and treat the patients battling lung cancer. We’re with you there right along helping you with that fight. And to your point, when I first started doing this I literally spoke to patients about chemotherapy. That’s what I had to offer. And it was just trying to make that selection process about which chemotherapy I thought was going to be right for you. And helping you with sequencing. “Okay, we’re gonna start with this and then we’re gonna plan for this and we’re gonna plan for that.”

And the game has completely changed, I think, with the genomic profiling. It is extremely important. We really have to go to these broad-based panels up front. And for right now, I just wanna emphasize tissue is the gold standard, but I really think that circulating tumor DNA is something that we can – certainly we’ve made a lot of significant progress and then can identify these mutations.

As you identify these mutations, checking them longitudinally over time to see how they evolve is gonna be very important. And that will help us continue to personalize treatment at what point do you pivot from a targeted therapy to a clinical trial to an immunotherapy to a chemotherapy. And all of these things come from sitting down, looking at the scans, looking at the patient, looking at these molecular reports, getting everybody on the same page and then making – again I think having a shared decision model. Setting, “What are your goals? What are your hopes?” And then making sure that we match that as best as we can.

Andrew Schorr:   

Wow. Get tested, folks.

Dr. Gray:                

Yes.

Andrew Schorr:   

Have your family member get tested and then raise the question with your team, “Do we needed to be tested again?” 

Dr. Gray:                

Yes. Yeah. 

Andrew Schorr:   

All right.

Dr. Gray:                

Absolutely.

Andrew Schorr:   

And then I think Dr. Gray, I just wanna underscore a point she made about your goals. 

Dr. Gray:                

Yes.

Andrew Schorr:   

So, Ed thinks about that. And Ed, I’m gonna give the final comments to you about speaking up for yourself.

Dr. Gray:                

Yes. 

Andrew Schorr:   

How do you get the care that’s right for you and how do you wanna live your life? I mean you and Donna wanna do some more traveling, right, Ed? I hope you can.

Edward Cutler:     

We’ve been very fortunate. No question about it. When I first got my diagnosis, I was devastated. I thought my world was gonna end in a year. But I started talking to my doctors, started talking to other patients in similar situations and I found that, yeah, there was hope. I put together a bucket list. And I found that my bucket list wasn’t gonna be limited to a year. So, I expanded my bucket list. And now it goes on at least ten years out now and I’m very hopeful of that.

As I said, I’ve spoken with a lot of patients here within Moffitt, around the state, around the country, and some internationally through support groups. And we help each other. We cry on each other’s shoulder and then we tell each other our problems. And somebody has an experience that they went through and it might be helpful to another patient. Now, I think it’s very important to open up your heart and open up your ears and your mind and listen to other people. Don’t just look at what you read on the internet. Who knows what the truth is what you read on the internet. A lot of it is – I don’t know. It’s not necessarily factual.

But I think if you talk to you doctors, to your team, and your team doesn’t include just your doctors. It’s your nurses, it’s the nurse’s aide, it’s the social worker, it’s the nutritionist.

Dr. Gray:                

No. 

Edward Cutler:     

All of these people can be very helpful for just about everybody who has an advanced diagnosis.

Andrew Schorr:   

Well said, Ed. We have this medical team here that represents some of those others that Dr. Boyle mentioned, the personalized medicine people, the pharmacist, you mentioned social workers. Before we have to go, I wanted to give you the chance if you want to say thank you to these folks or what they represent on behalf of patients. What would you wanna say?

Edward Cutler:     

I am just so thankful to every person that I’ve dealt with here at Moffitt. They have made the process if not the simplest thing in the world to deal with, pretty darn simple anyhow. My doctors have explained things to me that I didn’t even know how to ask the questions in some cases. And it’s just been wonderful. I’ve become an advocate for Moffitt. I talk to people in the community. I go to Tallahassee with a group of people and talk to our legislatures about funding for Moffitt. I’m participating in the Miles for Moffitt next month as a volunteer. Not as a runner, but as a volunteer, to help raise money for Moffitt to find if not the cure at least the way to extend someone’s life with good quality.

Andrew Schorr:   

Wow.

Edward Cutler:     

And I thank you all for that.

Andrew Schorr:   

We wish you all the best. I wanna say to our audience that could be anywhere in the world, I think the lesson of what Ed is saying is go to a center where they’re knowledgeable to at least get a second opinion, Dr. Boyle had mentioned that earlier, and connect with a team like this. And then when they help you and you’re given higher quality of life hopefully and longer life, then go to bat for other people. Whether it’s with your center, like Ed has, or in a state, speak out because you can help a lot of other people. I try to do that too.

Edward Cutler:     

One other thing, Andrew. I have another thank you. Well, it’s actually two other thank yous. First to my wife for being a great support. And second, to the man who had the vision to make Moffitt reality. And that is H. Lee Moffitt who at one point in time was the speaker of the house of the Florida legislature. It was his vision. Unfortunately, he had cancer and that generated his vision. But he’s still going strong and he’s still working very hard for this institution.

Andrew Schorr:   

Well, I wanna mention then lastly that we can all make a difference. The doctors making difference, patients, family members in that collaboration and in helping others. I wanna thank everybody for being with us today. I’m Andrew Schorr. Remember, knowledge can be the best medicine of all.


Please remember the opinions expressed on Patient Empowerment Network (PEN) are not necessarily the views of our sponsors, contributors, partners or PEN. Our discussions are not a substitute for seeking medical advice or care from your own doctor. That’s how you’ll get care that’s most appropriate for you.