September 13, 2024 • 13 mins
Welcome to episode one of three, where we dive deep into the challenges and advancements in managing locally Advanced or Metastatic EGFR+ Non-Small-Cell Lung Cancer (NSCLC). Join Dr. Mark Socinski, Executive Medical Director of the Advent Health Cancer Institute, and Dr. David Waterhouse from Oncology Hematology Care in Cincinnati, Ohio, as they discuss the importance of biomarker testing, the evolution of treatment strategies, and the impact of effective first-line therapies on patient outcomes.
Mark as Played
Transcript
Episode Transcript
Available transcripts are automatically generated. Complete accuracy is not guaranteed.
(00:00):
Music.
(00:05):
Welcome to the Unmet Needs in Locally Advanced or Metastatic EGFR Positive NSCLC
episode of the Practice to Practice podcast series.
This educational podcast is brought to you by Johnson & Johnson and is not certified
for continuing medical education.
The consultants in this podcast were paid by Johnson & Johnson and must present
(00:27):
information in compliance with FDA requirements applicable to Johnson & Johnson.
The thoughts and opinions expressed during this podcast are those of the speakers
and do not necessarily reflect the views or positions of Johnson & Johnson.
Mark, it's so good to see you again. We've been friends for an awful long time.
(00:48):
For the benefit of the people in the audience, would you mind introducing yourself?
Hello, my name is Dr. Mark Sosinski. I'm the Executive Medical Director of the
Advent Health Cancer Institute in Orlando, Florida.
I spend most of my time as an institute director and administrative in leadership roles.
However, I've retained my clinical practice in thoracic malignancies,
as well as various leadership committees, steering committees,
(01:10):
data safety monitoring committees.
Hi, I'm Dave Waterhouse. I am with OHC in Cincinnati, Ohio, a large single specialty
oncology group comprised of medical oncology, radiation, and gynecologic oncology.
Where I founded their research group and have remained passionate about community
research and thoracic oncology at different levels, working with several of
(01:33):
the different groups and together with ASCO.
David, in your practice, when you're thinking about advanced EGFR mutation positive
disease, that's kind of restricted to the common mutations.
Thinking about how you manage and treat and what you believe the unmet needs are in this population.
I wish there weren't unmet needs, but they certainly are.
And I would probably start with identifying patients as having a common EGFR
(01:59):
mutation. So biomarker testing.
As you know, the guidelines will state that every patient who we're going to
treat should have that information done and obtained, and you should wait for
the results before you embark on that first line of therapy.
Following that, if you get them on the right therapy based on their molecular
testing, I think that the next thing is to make sure you can make the right
(02:22):
choice for the agent that you're going to use.
And then, of course, unfortunately, a lot of patients won't make it to second line.
I'm always surprised that the testing rates are still as low as they are.
Not where they should be.
So, Mark, why is it important to perform the biomarker testing before first-line
treatment for locally advanced or metastatic non-small-cell lung cancer?
(02:44):
You know, the one thing we've learned about advanced-stage non-small-cell lung
cancer is that one size does not fit all.
This is a very heterogeneous disease. It's characterized by a number of mutations
and fusions that you have to test for.
We have a number of FDA-approved therapies. There are now nine or ten biomarkers.
In addition, there's PD-L1 testing that is informative in terms of how we use immunotherapy.
(03:04):
So I think you want to make the right choice for the patient in that first-line
setting in knowing all of those 9 or 10 biomarkers as well as the PD-L1 status
before you make your first-line treatment decision.
We are responsible as their oncologists for making that first-line treatment
choice, and we must get it right every time in every patient, in my opinion.
(03:25):
I couldn't agree with you more. We wouldn't treat a breast cancer
without knowing exactly er pr or her too and
yet somehow it's okay to treat a lung cancer without knowing
the biomarkers yeah i agree with you yeah so david
in a patient with advanced metastatic non-small cell what's your strategy in
terms of how you perform biomarker testing things like tissue versus plasma
(03:48):
are you doing broad-based ngs testing are you doing pcr based testing or what's your strategy?
I think the strategy has been evolving over time.
Certainly, we prefer to have NGS testing and, of course, IHC for PD-L1.
I think the days of PCR and spot testing are gone.
(04:08):
I think a more difficult part of this is if you live in a resource-rich environment,
you have the luxury of sending off a tissue test and even a liquid biopsy at the same time.
But if you live in a place where there's either insurance restrictions or institutional
restrictions, I think you have to be a little bit more conservative.
(04:29):
Generally, I want to prioritize tissue if there is enough tissue.
Been leaning more towards getting both asking for tissue, but also sending off
a liquid biopsy when I think it's going to fail, most likely EVUS or when they're having cytology,
either a fine needle from navigational or cytology on a pleural effusion,
(04:51):
something of that nature.
Are you confident that you're getting all that information before you make your decision?
I want to be confident. I know that there's sometimes some differences between the different vendors.
I I think that will continue to evolve as the testing becomes more and more standardized.
I think it's more important to have one vendor and be comfortable with getting
(05:15):
their report, having a relationship with them to talk about those issues when
you need to, having that call me button.
Yeah, I couldn't agree more. In my practice, I think one of the greatest things
we do is identify a driver mutation or fusion.
Those patients have access to very effective targeted
therapies they tend to do better in general and I
(05:35):
in my practice I do both tissue in in
plasma kind of at the same time now the false negative with plasma is an issue
and in physicians have to know about it this is where your point about have
a relationship with it with whatever testing company you're working with so
that you understand their technology understand their limitations where they
are and understand the limitations of tissue understand the limitations of plasma.
(05:58):
And then you'll be more informed and more likely to make the right decision in the patient.
So, Mark, what percentage of your locally advanced or metastatic non-small cell
lung cancer patients are positive for common EGFR mutations?
So we test everybody. In my practice, I would say it's in the range for the
common mutations, 10 to 15 percent or so.
(06:20):
That's in a central Florida population.
You know, it's going to vary depending upon your population.
If you have more never smokers, more of an Asian population,
that percentage will go up. I think Cincinnati, it might actually be a shade
lower. As you said, it's geographically dependent.
We have a much higher smoking rate. True. Part of the nation.
And, you know, you talk to our friends on the West Coast where they're enriched
(06:43):
for Asian populations. Yeah.
You know, 25 to 30 percent of their practice is EGFR mutations.
But you said something really important at the beginning. You still test everybody. Yes, absolutely.
It used to be we would use clinical factors for whether or not to test.
And all that should be kind of flushed away.
And the only thing is the histologic diagnosis of non-small cell. Yes.
(07:07):
David, we've been focusing mostly on the common EGFR mutations,
the exon 19 deletions and the LA58R exon 21 mutation.
What other EGFR mutations do you tend to see in your clinical practice?
Well, I mentioned earlier, we don't see as much. But if you test everybody,
you're going to find them.
Just recently, I had a patient with an exon 20 insertion mutation.
(07:29):
Yeah, you know, we're in a situation where 80 to 85% of the EGFR mutations will
be the common mutations, but there's the uncommon ones.
People don't understand that the EGFR insertions, well over 100 insertions described
in that population, which underscores the limitations of PCR-based testing.
And that's why next-generation sequencing. Exactly.
(07:50):
In my practice, it's only NGS.
Why is it so important to use the most effective and appropriate treatment first
for patients with locally advanced or metastatic EGFR positive,
again, we'll talk common mutation patients with non-small cell lung cancer?
The data suggests that what you do first makes the biggest impact.
(08:11):
And you can't always assume that you're going to get a so-called second shot
on goal with second line therapy.
We know from national figures that there's a huge dropout from first line to
second line. It would be a tragedy if a patient with a driver like a common
EGFR mutation didn't get a targeted therapy. But we know that happens.
But I hate it when someone says, I'm saving that for second line or later.
(08:35):
Yeah, no, that's the exact wrong way to think about it, because the biggest
impact you're going to have is in the first line setting.
And again, this is why we go through all the comprehensive molecular testing.
And again, if you test and you find something, you must act on it.
You must get that patient the appropriate targeted therapy.
When I think of a patient, I think of everything they're tied to.
(08:57):
Parents, kids, grandkids, life events, all these sorts of things.
And my job is to make them experience as much of that as they possibly can.
And that really compels us to get the right treatment, right patient,
right time, so that you give the patient the opportunity to have as long a good
quality of life as they possibly can. Yeah, and it can make a big difference
(09:19):
whether you get the right one or not.
David, in your practice, when you treat patients with EGFRM common mutations.
What do you see for outcomes in these patients in terms of disease control,
survival, these sorts of things?
You mentioned getting the right patient on the right drug. And I think this
is one of the patient populations where you feel real good about it often because
(09:42):
they do better than what we used to expect from our patients with non-small cell lung cancer.
In my practice, you know, I generally talk to patients about progression-free
survival, really control of their disease.
My expectation is, you know, 18 to
20 plus months of disease control with appropriate and effective therapy.
(10:04):
Survival, we know, is on average slightly more than three years.
So many of these patients, again, with appropriate therapy will do relatively well.
It still is quite a difference though. I mean, coming out of fellowship,
we told patients with metastatic lung cancer, three, maybe six months,
and get your affairs in order.
And now with the appropriate therapy, we're thinking about measuring progression-free
(10:29):
survival in years, never mind overall survival.
And it hasn't always been that way. Too very difficult to treat cancers,
melanoma and lung cancer, which historically were felt to be difficult to treat,
if at all, treatable cancers.
Now, because of the array of targeted therapies and immunotherapy impact,
(10:50):
we're doing much better in these difficult cancers.
Very much so. It's been very satisfying in that regard.
People have always said, how do you become a lung cancer doc?
And we can tell them that actually we've made a huge difference.
And it is very satisfying to see these patients do well.
I think the important message out there that I think starts with the physician,
(11:13):
but it goes through all of our health care providers, is that patients with
lung cancer should be given hope and we should be optimistic about the potential outcome.
We don't have a good outcome in every patient. I don't want to lead people to
believe that everything is good.
No, we have still a lot of work to do, but we've accomplished a lot in this
disease. and rather than look at this as a disease in which the treatment benefits
(11:37):
are rather marginal, I think the treatment benefits can be incredible.
And I think every patient I see is going to be one of those incredible patients
that's going to live for years with effective and appropriate therapy.
Mark, it's been just a joy talking to you about this again today. You know.
I went into private practice because I was told that spending a career trying
(12:01):
to do thoracic oncology was career-ending.
And yet, look how far we've come. This journey has been a lot of fun,
and it's so impactful for our patients. I'm curious about your thoughts.
If you had told me 30, 35 years ago that lung cancer would be this interesting
and this diverse, and we would have the number of options that we have nowadays
(12:24):
to treat our patients, I'm not sure I would have believed it.
You know, we're about to celebrate the 20-year anniversary of the discovery
report of EGFR mutations in 2004.
And when I think back to that 20 years in terms of what we know now compared to what we knew in 2004,
when that New England Journal paper and the science paper came out and described
(12:44):
these patients that were having these lights-out responses to oral therapies,
you know, we've come a long way with understanding how to use these drugs.
And I think we're on the verge of learning a lot more about how to maximize
first-line treatment for these patients.
And I think we'll continue to see improvement in outcomes.
Thank you. Thank you. This episode was approved under CP-429518-V1.
(13:10):
For more practice-to-practice podcasts, videos, and other information on locally
advanced or metastatic EGFR-positive NSCLC, please visit egfrroutes.com.
Music.
(00:05):
Welcome to the Unmet Needs in Locally Advanced or Metastatic EGFR Positive NSCLC
episode of the Practice to Practice podcast series.
This educational podcast is brought to you by Johnson & Johnson and is not certified
for continuing medical education.
The consultants in this podcast were paid by Johnson & Johnson and must present
(00:27):
information in compliance with FDA requirements applicable to Johnson & Johnson.
The thoughts and opinions expressed during this podcast are those of the speakers
and do not necessarily reflect the views or positions of Johnson & Johnson.
Mark, it's so good to see you again. We've been friends for an awful long time.
(00:48):
For the benefit of the people in the audience, would you mind introducing yourself?
Hello, my name is Dr. Mark Sosinski. I'm the Executive Medical Director of the
Advent Health Cancer Institute in Orlando, Florida.
I spend most of my time as an institute director and administrative in leadership roles.
However, I've retained my clinical practice in thoracic malignancies,
as well as various leadership committees, steering committees,
(01:10):
data safety monitoring committees.
Hi, I'm Dave Waterhouse. I am with OHC in Cincinnati, Ohio, a large single specialty
oncology group comprised of medical oncology, radiation, and gynecologic oncology.
Where I founded their research group and have remained passionate about community
research and thoracic oncology at different levels, working with several of
(01:33):
the different groups and together with ASCO.
David, in your practice, when you're thinking about advanced EGFR mutation positive
disease, that's kind of restricted to the common mutations.
Thinking about how you manage and treat and what you believe the unmet needs are in this population.
I wish there weren't unmet needs, but they certainly are.
And I would probably start with identifying patients as having a common EGFR
(01:59):
mutation. So biomarker testing.
As you know, the guidelines will state that every patient who we're going to
treat should have that information done and obtained, and you should wait for
the results before you embark on that first line of therapy.
Following that, if you get them on the right therapy based on their molecular
testing, I think that the next thing is to make sure you can make the right
(02:22):
choice for the agent that you're going to use.
And then, of course, unfortunately, a lot of patients won't make it to second line.
I'm always surprised that the testing rates are still as low as they are.
Not where they should be.
So, Mark, why is it important to perform the biomarker testing before first-line
treatment for locally advanced or metastatic non-small-cell lung cancer?
(02:44):
You know, the one thing we've learned about advanced-stage non-small-cell lung
cancer is that one size does not fit all.
This is a very heterogeneous disease. It's characterized by a number of mutations
and fusions that you have to test for.
We have a number of FDA-approved therapies. There are now nine or ten biomarkers.
In addition, there's PD-L1 testing that is informative in terms of how we use immunotherapy.
(03:04):
So I think you want to make the right choice for the patient in that first-line
setting in knowing all of those 9 or 10 biomarkers as well as the PD-L1 status
before you make your first-line treatment decision.
We are responsible as their oncologists for making that first-line treatment
choice, and we must get it right every time in every patient, in my opinion.
(03:25):
I couldn't agree with you more. We wouldn't treat a breast cancer
without knowing exactly er pr or her too and
yet somehow it's okay to treat a lung cancer without knowing
the biomarkers yeah i agree with you yeah so david
in a patient with advanced metastatic non-small cell what's your strategy in
terms of how you perform biomarker testing things like tissue versus plasma
(03:48):
are you doing broad-based ngs testing are you doing pcr based testing or what's your strategy?
I think the strategy has been evolving over time.
Certainly, we prefer to have NGS testing and, of course, IHC for PD-L1.
I think the days of PCR and spot testing are gone.
(04:08):
I think a more difficult part of this is if you live in a resource-rich environment,
you have the luxury of sending off a tissue test and even a liquid biopsy at the same time.
But if you live in a place where there's either insurance restrictions or institutional
restrictions, I think you have to be a little bit more conservative.
(04:29):
Generally, I want to prioritize tissue if there is enough tissue.
Been leaning more towards getting both asking for tissue, but also sending off
a liquid biopsy when I think it's going to fail, most likely EVUS or when they're having cytology,
either a fine needle from navigational or cytology on a pleural effusion,
(04:51):
something of that nature.
Are you confident that you're getting all that information before you make your decision?
I want to be confident. I know that there's sometimes some differences between the different vendors.
I I think that will continue to evolve as the testing becomes more and more standardized.
I think it's more important to have one vendor and be comfortable with getting
(05:15):
their report, having a relationship with them to talk about those issues when
you need to, having that call me button.
Yeah, I couldn't agree more. In my practice, I think one of the greatest things
we do is identify a driver mutation or fusion.
Those patients have access to very effective targeted
therapies they tend to do better in general and I
(05:35):
in my practice I do both tissue in in
plasma kind of at the same time now the false negative with plasma is an issue
and in physicians have to know about it this is where your point about have
a relationship with it with whatever testing company you're working with so
that you understand their technology understand their limitations where they
are and understand the limitations of tissue understand the limitations of plasma.
(05:58):
And then you'll be more informed and more likely to make the right decision in the patient.
So, Mark, what percentage of your locally advanced or metastatic non-small cell
lung cancer patients are positive for common EGFR mutations?
So we test everybody. In my practice, I would say it's in the range for the
common mutations, 10 to 15 percent or so.
(06:20):
That's in a central Florida population.
You know, it's going to vary depending upon your population.
If you have more never smokers, more of an Asian population,
that percentage will go up. I think Cincinnati, it might actually be a shade
lower. As you said, it's geographically dependent.
We have a much higher smoking rate. True. Part of the nation.
And, you know, you talk to our friends on the West Coast where they're enriched
(06:43):
for Asian populations. Yeah.
You know, 25 to 30 percent of their practice is EGFR mutations.
But you said something really important at the beginning. You still test everybody. Yes, absolutely.
It used to be we would use clinical factors for whether or not to test.
And all that should be kind of flushed away.
And the only thing is the histologic diagnosis of non-small cell. Yes.
(07:07):
David, we've been focusing mostly on the common EGFR mutations,
the exon 19 deletions and the LA58R exon 21 mutation.
What other EGFR mutations do you tend to see in your clinical practice?
Well, I mentioned earlier, we don't see as much. But if you test everybody,
you're going to find them.
Just recently, I had a patient with an exon 20 insertion mutation.
(07:29):
Yeah, you know, we're in a situation where 80 to 85% of the EGFR mutations will
be the common mutations, but there's the uncommon ones.
People don't understand that the EGFR insertions, well over 100 insertions described
in that population, which underscores the limitations of PCR-based testing.
And that's why next-generation sequencing. Exactly.
(07:50):
In my practice, it's only NGS.
Why is it so important to use the most effective and appropriate treatment first
for patients with locally advanced or metastatic EGFR positive,
again, we'll talk common mutation patients with non-small cell lung cancer?
The data suggests that what you do first makes the biggest impact.
(08:11):
And you can't always assume that you're going to get a so-called second shot
on goal with second line therapy.
We know from national figures that there's a huge dropout from first line to
second line. It would be a tragedy if a patient with a driver like a common
EGFR mutation didn't get a targeted therapy. But we know that happens.
But I hate it when someone says, I'm saving that for second line or later.
(08:35):
Yeah, no, that's the exact wrong way to think about it, because the biggest
impact you're going to have is in the first line setting.
And again, this is why we go through all the comprehensive molecular testing.
And again, if you test and you find something, you must act on it.
You must get that patient the appropriate targeted therapy.
When I think of a patient, I think of everything they're tied to.
(08:57):
Parents, kids, grandkids, life events, all these sorts of things.
And my job is to make them experience as much of that as they possibly can.
And that really compels us to get the right treatment, right patient,
right time, so that you give the patient the opportunity to have as long a good
quality of life as they possibly can. Yeah, and it can make a big difference
(09:19):
whether you get the right one or not.
David, in your practice, when you treat patients with EGFRM common mutations.
What do you see for outcomes in these patients in terms of disease control,
survival, these sorts of things?
You mentioned getting the right patient on the right drug. And I think this
is one of the patient populations where you feel real good about it often because
(09:42):
they do better than what we used to expect from our patients with non-small cell lung cancer.
In my practice, you know, I generally talk to patients about progression-free
survival, really control of their disease.
My expectation is, you know, 18 to
20 plus months of disease control with appropriate and effective therapy.
(10:04):
Survival, we know, is on average slightly more than three years.
So many of these patients, again, with appropriate therapy will do relatively well.
It still is quite a difference though. I mean, coming out of fellowship,
we told patients with metastatic lung cancer, three, maybe six months,
and get your affairs in order.
And now with the appropriate therapy, we're thinking about measuring progression-free
(10:29):
survival in years, never mind overall survival.
And it hasn't always been that way. Too very difficult to treat cancers,
melanoma and lung cancer, which historically were felt to be difficult to treat,
if at all, treatable cancers.
Now, because of the array of targeted therapies and immunotherapy impact,
(10:50):
we're doing much better in these difficult cancers.
Very much so. It's been very satisfying in that regard.
People have always said, how do you become a lung cancer doc?
And we can tell them that actually we've made a huge difference.
And it is very satisfying to see these patients do well.
I think the important message out there that I think starts with the physician,
(11:13):
but it goes through all of our health care providers, is that patients with
lung cancer should be given hope and we should be optimistic about the potential outcome.
We don't have a good outcome in every patient. I don't want to lead people to
believe that everything is good.
No, we have still a lot of work to do, but we've accomplished a lot in this
disease. and rather than look at this as a disease in which the treatment benefits
(11:37):
are rather marginal, I think the treatment benefits can be incredible.
And I think every patient I see is going to be one of those incredible patients
that's going to live for years with effective and appropriate therapy.
Mark, it's been just a joy talking to you about this again today. You know.
I went into private practice because I was told that spending a career trying
(12:01):
to do thoracic oncology was career-ending.
And yet, look how far we've come. This journey has been a lot of fun,
and it's so impactful for our patients. I'm curious about your thoughts.
If you had told me 30, 35 years ago that lung cancer would be this interesting
and this diverse, and we would have the number of options that we have nowadays
(12:24):
to treat our patients, I'm not sure I would have believed it.
You know, we're about to celebrate the 20-year anniversary of the discovery
report of EGFR mutations in 2004.
And when I think back to that 20 years in terms of what we know now compared to what we knew in 2004,
when that New England Journal paper and the science paper came out and described
(12:44):
these patients that were having these lights-out responses to oral therapies,
you know, we've come a long way with understanding how to use these drugs.
And I think we're on the verge of learning a lot more about how to maximize
first-line treatment for these patients.
And I think we'll continue to see improvement in outcomes.
Thank you. Thank you. This episode was approved under CP-429518-V1.
(13:10):
For more practice-to-practice podcasts, videos, and other information on locally
advanced or metastatic EGFR-positive NSCLC, please visit egfrroutes.com.
Popular Podcasts
Stuff You Should Know
If you've ever wanted to know about champagne, satanism, the Stonewall Uprising, chaos theory, LSD, El Nino, true crime and Rosa Parks, then look no further. Josh and Chuck have you covered.
Dateline NBC
Current and classic episodes, featuring compelling true-crime mysteries, powerful documentaries and in-depth investigations. Follow now to get the latest episodes of Dateline NBC completely free, or subscribe to Dateline Premium for ad-free listening and exclusive bonus content: DatelinePremium.com
On Purpose with Jay Shetty
I’m Jay Shetty host of On Purpose the worlds #1 Mental Health podcast and I’m so grateful you found us. I started this podcast 5 years ago to invite you into conversations and workshops that are designed to help make you happier, healthier and more healed. I believe that when you (yes you) feel seen, heard and understood you’re able to deal with relationship struggles, work challenges and life’s ups and downs with more ease and grace. I interview experts, celebrities, thought leaders and athletes so that we can grow our mindset, build better habits and uncover a side of them we’ve never seen before. New episodes every Monday and Friday. Your support means the world to me and I don’t take it for granted — click the follow button and leave a review to help us spread the love with On Purpose. I can’t wait for you to listen to your first or 500th episode!