Challenging Cases in Lung Cancer:
Acquired Resistance to Tarceva (erlotinib) in a Previously Responding
Patient with Advanced NSCLC and an Activating EGFR Mutation
Dr. West:
Hello and welcome. My name is Dr. Jack West, and I’m a medical oncologist and the Founder
and CEO of GRACE, the Global Resource for Advancing Cancer Education. Our program today is
made possible through generous support from the LUNGevity Foundation.
This is part of a series of podcasts covering challenging clinical cases in lung cancer that don’t
have a clear correct answer for the best treatment based on the evidence, and they therefore
require our best judgment as experts consider the options and the merits of one approach over
another.
This is part of a series of podcasts covering challenging clinical cases in lung cancer that don’t
have a clear correct answer for the best treatment based on the evidence, and they therefore
require our best judgment as experts consider the options and the merits of one approach over
another.
The same series of cases was discussed with multiple experts in the field of lung cancer from
several different institutions to provide a better sense of where there is consensus and where
there is still a wide range of treatment styles that might all be considered appropriate.
Each podcast starts with a brief thumbnail of a case presentation and them discussion from a live
program done with Dr. Robert Doebele, Assistant Professor of Medical Oncology at the University
of Colorado Medical Center in Denver, and Dr. Jyoti Patel, Associate Professor of Medical
Oncology at the Feinberg School of Medicine at Northwestern University in Chicago.
The discussions will then continue with commentary by the several other clinical experts,
including:
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Dr. Suresh Ramalingam, from Winship Cancer Center, Emory University in Atlanta, GA,
Dr. Jonathan Goldman, from Premier Oncology in Santa Monica, CA.
Dr. Julie Brahmer, from Sydney Kimmel Cancer Center at Johns Hopkins University, in
Baltimore, MD
Dr. Heather Wakelee, from Stanford University Cancer Center in Palo Alto, CA
Dr. Karen Reckamp, from City of Hope Cancer Center in Duarte, CA
So, let’s move on to advanced disease. This particular patient is a 73 year old Asian neversmoking man with a lung adenocarcinoma and multiple liver metastases at the time of his
presentation. His initial biopsy also has tissue sent for molecular testing with shows an activating
EGFR mutation.
He has a great initial response to Tarceva, as we do often see in patients with an EGFR mutation.
That’s his first line of therapy. But around 14 months after he starts that, he shows on his scan
some modest but convincing progression. It’s still less than he started with, but it’s clear that
there is progression happening now. So, my initial question is, when are you inclined to make a
change versus are you inclined to sometimes watch people as they’re progressing in this
situation? Then, once you do decide to make a change what are you inclined to do? Maybe I can
start with Bob.
He has a great initial response to Tarceva, as we do often see in patients with an EGFR mutation.
That’s his first line of therapy. But around 14 months after he starts that, he shows on his scan
some modest but convincing progression. It’s still less than he started with, but it’s clear that
there is progression happening now. So, my initial question is, when are you inclined to make a
change versus are you inclined to sometimes watch people as they’re progressing in this
situation? Then, once you do decide to make a change what are you inclined to do? Maybe I can
start with Bob.
Dr. Doebele:
Sure. So, I think one thing I guess I’d like to say before even getting into how you’d handle this
low progression is that recently it’s been recommended that patients undergo an EGFR mutation
testing and I think that it’s important to consider EGFR mutation testing in all patients, not just
those that fit a particular clinical phenotype. We are in the practice at University of Colorado of
testing all of our patients. That includes squamous, which admittedly are incredibly rare. But we
have found EGFR mutations in that patient population. But there is a recent JCO article
documenting that approximately 40% of all mutations occur in current or former smokers. So I
think one important thing to really consider we should do our patients a favor and consider
mutation testing in all of them.
Having said that, the progression issue is a very interesting one. What I can say is, if there is a
single lesion that’s growing, we would typically consider biopsy of that lesion. Especially if it’s
readily accessible and I know this is going to come up in a minute. It might lead to a clinical trial.
The other important thing is, if it’s only a single lesion that’s growing, I think you can approach this
with local therapy. So, radiation, SBRT, whether it’s in the liver or bone or lung.
And then consider the Tarceva. I think that’s, perhaps, one of the easier situations, even though I
don’t think we have great evidence to support that. I think it’s a very reasonable strategy. If
there’s only a single lesion that’s growing, we know that there can be clonal variation and only one
of them metastatic sites might have resistance. So, not easier. If there are multiple sites that are
slowly growing, I think that it is a more difficult question, but I am willing to allow my patients to
have slow growing progression. After having done this many times, it can be six or eight months
before there is more significant progression requiring a change in therapy.
Dr. West:
What is your approach when they do progress enough to make a change in the systemic therapy?
Dr. Doebele:
So, we of course we would prefer clinical trial. There are multiple trials trying to evaluate
combination therapies that may target specific mechanisms of resistance, so whether it’s MET
amplification or T790M, there are strategies that are meant to target each of those. That would be
our preferred modality. But for someone like this if a clinical trial is not available nearby, then I
would consider first line chemotherapy with platinum and another agent. Those patients have very
good response rates for me. I pass the response rates for EGFR mutations patients was twice
that of EGFR wild type. So these patients do quite well with chemotherapy. So I think, for this
patient, if I was going to switch, if I didn’t have access to a clinical trial or he didn’t fit the criteria, I
would do a platinum based chemotherapy.
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Dr. West:
And not continue the EGFR inhibitor?
Dr. Doebele:
Yeah, and not continue the EGFR inhibitor because of problems showing, studies showing
antagonism between those two agents.
Dr. West:
I can turn to Jyoti. Dr. Patel, I know you see plenty of these patients as well. What is your
approach to somebody who is a slow to modest progression after enjoying a good, prolonged
response?
Dr. Patel:
It absolutely depends on how the patient is tolerating the Tarceva and how many sites of
progression there are. If it is solitary reoccurrence, I think the strategy of giving local therapy
makes a lot of sense. In patients who are symptomatic from their disease or have more
worrisome progression in multiple organs, then we’re more likely to suggest that they either,
again, go into a clinical trial or that they begin chemotherapy. So, one of the clinical trial that we
have right now Melissa Johnson’s work is with a Novartis drug AUY922, which is a heat shock
protein 90 inhibitor. And that is targeted at the mutation that Bob mentioned, the T790M mutation.
So we give the drugs because it attacks the chaperone protein. We think it’s circumvents the new
mutation. So patients stay on their Erlotinib and get this weekly infusion. This is very early. It’s
phase one, but we hope that it will be effective. More often, patients elect to go on systemic
chemotherapy. Again, depending upon how much progression they’ve had and what their quality
of life is. Sometimes I’ll, if it’s just minor progression, I may add another targeted drug. I have
certainly added Avastin to the patients who are on Tarceva and we’ve seen some nice results.
Usually I’ll add the drug Alimta either with platinum or without. We’ll plan to do sort of discreet
chemotherapy. So I’ll say we’ll probably do 4 cycles and at that time, I’ll give you a break off of
the systemic therapy if you have the nice response I would hope. Now I am one of those that
believes that if you have an EGFR addicted tumor then you should probably stay on Tarceva
despite the progression.
There’s been some nice work from Greg Riley at Memorial Sloane Kettering where he showed
sort of a flared response in patients who are off for a couple of weeks. The tumor may pick up.
So I generally continue Tarceva, especially if patients are tolerating it and haven’t had any toxicity.
I’m very happy giving the full dose. Sometimes we know that people have difficulties or have
upset stomach. At that time, I’ll usually hold the Tarceva for five days around the chemotherapy
and hope that would address any concerns about antagonism. But I tend to keep the Tarceva
going.
Dr. West:
Great.
Dr. Patel:
With no data.
Dr. West:
But I think most of us are struggling with a lack of data of this approach here. Bob you already
spoke to this. Do you routinely recommend repeat biopsy after patients develop a required
resistance to an oral therapy. If so, has it been very straight forward to get that covered by
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insurance, or is that a barrier? Then also, what can we use that information for right now? Jyoti,
why don’t’ I start with you?
Dr. Patel:
Generally, we do repeat biopsies as part of clinical trial. There are patients though that I’ve
biopsied because their phenotypes or changes clinically they’re behaving different than they did.
It’s not the slow progression. That things have picked up pace. I started doing that after Lecia
Sequist presented some of her data that she had patient sort of change histology. They end up
having sort of a change from the well differentiate adenocarcinoma, for example, to a cancer with
no endocrine or small-cell features. We’ve picked up a couple of these patients. That case is a
huge paradigm shift in their treatment. And, my feeling is then it’s very worthwhile because the
drugs that you give are completely different. We have not had problems with payment or
insurance coverage. I may have had some problems with the radiologist asking me why I’m
asking for a biopsy again. But now that they’re seeing some of our strategies more and more
people are comfortable with it. And patients are also generally willing to find out what has
changed about their cancer, particularly those who have had a nice period of disease control on
Tarceva.
Dr. West:
Bob, what’s your experience in Colorado?
Dr. Doebele:
Yeah, I would completely echo what Jyoti said in that we’ve also seen the small-cell trend
transitions in which the chemotherapies or the therapies you would use are very different.
Typically what we’re seeing is, all of a sudden, a more explosive progression, not this kind of slow
or solitary progression. I think, in that case, there is no evidence that a good number of these
resistance cases are small-cell conversions in which case I think it would be clinically indicated.
We have not had trouble with insurance paying. I don’t know how attuned they are to the issues of
why we’re doing the biopsy. But so far we have not had a lot of rejections.
We’ve worked really closely with our interventional radiologist because it, I think, it’s very
important when we’re going to re-biopsy, that they re-biopsy the right lesion. That this is a rebiopsy. If there is multiple lesions in the liver, you need to biopsy the one that’s growing. So we
often have a very detailed discussion about making sure that they can biopsy the lesion that we’re
interested in, the one that’s growing, to determine the mechanism. I also agree that the patients
are very interested. Beyond the small-cell conversion, at this point, we do potentially use that
information to direct them towards the clinical trial. If they have T7 90M, one option is to do
Cetuximab plus an irreversible EGFR TKI, William Pao study. If they have MET, you might try
Crizotinib plus an irreversible EGFR or Pan HER inhibitor.
So I think the information is useful, but not all of it is going to lead to a standard of care as next
therapy. But I think the small-cell conversion is an important one to But I think most of us are
struggling with a lack of data of this approach here. Bob you already spoke to this. Do you
routinely recommend repeat biopsy after patients develop a required resistance to an oral
therapy. If so, has it been very straight forward to get that covered by insurance, or is that a
barrier? Then also, what can we use that information for right now? Jyoti, why don’t’ I start with
you?
Dr. Patel:
Generally we do repeat biopsies as part of clinical trial. There are patients though that I’ve
biopsied because their phenotypes or changes clinically they’re behaving different than they did.
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It’s not the slow progression. That things have picked up pace. I started doing that after Lecia
Sequist presented some of her data that she had patient sort of change histology. They end up
having sort of a change from the well differentiate adenocarcinoma, for example, to a cancer with
no endocrine or small-cell features. We’ve picked up a couple of these patients. That case is a
huge paradigm shift in their treatment. And, my feeling is then it’s very worthwhile because the
drugs that you give are completely different. We have not had problems with payment or
insurance coverage. I may have had some problems with the radiologist asking me why I’m
asking for a biopsy again. But now that they’re seeing some of our strategies more and more
people are comfortable with it. And patients are also generally willing to find out what has
changed about their cancer, particularly those who have had a nice period of disease control on
Tarceva.
Dr. West:
Bob, what’s your experience in Colorado?
Dr. Doebele:
Yeah, I would completely echo what Jyoti said in that we’ve also seen the small-cell trend
transitions in which the chemotherapies or the therapies you would use are very different.
Typically what we’re seeing is, all of a sudden, a more explosive progression, not this kind of slow
or solitary progression. I think, in that case, there is no evidence that a good number of these
resistance cases are small-cell conversions in which case I think it would be clinically indicated.
We have not had trouble with insurance paying. I don’t know how attuned they are to the issues of
why we’re doing the biopsy. But so far we have not had a lot of rejections.
We’ve worked really closely with our interventional radiologist because it, I think, it’s very
important when we’re going to re-biopsy, that they re-biopsy the right lesion. That this is a rebiopsy. If there is multiple lesions in the liver, you need to biopsy the one that’s growing. So we
often have a very detailed discussion about making sure that they can biopsy the lesion that we’re
interested in, the one that’s growing, to determine the mechanism. I also agree that the patients
are very interested. Beyond the small-cell conversion, at this point, we do potentially use that
information to direct them towards the clinical trial. If they have T7 90M, one option is to do
Cetuximab plus an irreversible EGFR TKI. William Powell study. If they have MET, you might try
Crizotinib plus an irreversible EGFR or Pan HER inhibitor.
So I think the information is useful, but not all of it is going to lead to a standard of care as next
therapy. But I think the small-cell conversion is an important one to consider and we’ve definitely
seen that.
Dr. Suresh Ramalingam, Winship Cancer Center, Emory University, Atlanta, GA:
For a patient who is progressing very slowly but still the disease burden is much less than we
started off with, my tendency is to continue them on the Tarceva until there is either new
symptoms or new areas of metastatic disease that would require us to shift course. The reason
here is we don’t really have very specific targeted strategies to overcome resistance, though we
are making some progress in terms of early results from clinical trials. So my approach is giving
the Tarceva for slow progression, and when it is time to change, I go to combination
chemotherapy if the patient has not received it before.
There are some groups who believe that tarceva should be continued with chemotherapy if they
develop progression, but I think that approach has not been firmly tested in a clinical trial, so I
switch to combination chemotherapy if there was no specific clinical trial available for these
patients.
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Dr. West:
Do you ever go back to rechallenge them with an EGFR inhibitor again?
Dr. Ramalingam:
I have done that after I have given 1 or 2 chemotherapy regimens, and I would say that in most
instances I have not seen a major response. Perhaps the best I have seen is short-lived
stabilization of disease.
Dr. Ramalingam:
When I run out of standard options, I have done that.
Dr. West:
In this kind of setting, do you recommend a repeat biopsy after a patient develops acquired
resistance to an oral EGFR inhibitor, and if so, do you tend to encounter much of a challenge in
terms of payment for that? Insurance coverage and just the practical aspects of pursuing it?
Dr. Ramalingam:
I think obtaining a biopsy would give us the information on the mechanism of resistance, and from
an academic standpoint, this is of great interest to all of us. In terms of what we do with this
information at this time for a patient outside of a clinical trial, the answer is we don’t have specific
treatments to offer. So if an institution has a trial that would specifically address an EGFR
resistance situation based on the mechanism, it would be reasonable to do a biopsy. Outside of
that, at this point, I’m not recommending a repeat biopsy, but if a patient is willing from an
academic standpoint, I think it makes great sense to get one.
Dr. Jonathan Goldman, Premier Oncology, Santa Monica, CA:
Well this is a case where you have lots of options. Nothing is clearly been shown to be better
than another approach. The obviously a clinical trial for a second generation EGFR inhibitor
would be promising way to go. At the same time, we haven’t had a lot of success in that direction
as of yet. I tend to use the Tarceva for longer than I would other treatments. I think that a lot of
times, even with progression, patient is still having benefit and so I’d like to be convinced that
there is real progression, not just increased PET activity, but real growth, for example.
And at that point, in this case, I think there have not been any prior chemotherapy, so I’d tell the
patient in general not only did you have the good mutational make up to have a good response to
Tarceva, you also have the good makeup to have a good response to chemotherapy. Many times
I’ll switch to a platinum doublet. I see this patient as adenocarcinoma and so Olympta, Cisplatin
or Carboplatin I think is very reasonable. You could even use Avastin, depending on the other
criteria that the patient has. I tend not to include or continue Tarceva at that point. I’ve been very
convinced by several case series showing multiple retreatments with Tarceva gives you, or in
other cases Iressa, gives you repeat responses. I’ve seen some cases up to seven retreatments.
Not that that’s going to be every patient. What I try to do is plan with a patient that at some point,
we’ll likely go back to Tarceva and it might be after four cycles of the platinum doublet. And the
idea would be that the chemotherapy is eradicating or minimizing the Tarceva resistant clones.
Then you’re going back to the Tarceva as more a maintenance strategy at that point. But I really
don’t think that anyone’s figured this problem out yet.
Dr. West:
Do you currently request a re-biopsy of tissue after a patient develops required resistance to an
EGFR tyrosine kinase inhibitor?
Page 6 of 10
Dr. Goldman:
I think I’m more aggressive than most in suggesting to a patient to get a re-biopsy. Some people
are very clear they don’t want to go through that again and I don’t think there’s a reason to really
push someone. But other patients, I think, are not too off put by it. In fact, I think it’s oncologists
that have tended not to ask the patient. I think there, unfortunately at the same time, it’s not
always clear what to do with the information of the biopsy. But sometimes we do find, for
example, that we may want to move them to a specific clinical trial at another trial depending on
what we find. I certainly think that if the patient is interesting in being part of the growing
understanding of Tarceva, when it works and when it doesn’t. then I think a lot of patients are
willing to do that. It also depends a lot on where they have tumor. A liver biopsy can usually be
done very safely. A central lung mass might be more concerning.
Dr. Julie Brahmer, Sydney Kimmel Cancer Center, Johns Hopkins University, Baltimore, MD:
Depending on the patient. If there is minimal change, but even though if it’s just one spot slowly
growing and everything else is pretty quiet, then I won’t make a change. Certainly if things start
picking up and start increasing then I’ll for sure try to push the dose as high as the patient can
tolerate up to the maximum dose. For us in the U.S., Tarceva 150 mg a day. If that doesn’t work,
then I’m torn between switching completely to just chemotherapy or potentially leaving that patient
on Tarceva and adding chemotherapy to it. I don’t think I have convincing evidence to do either.
A lot will depend on how the patient is doing. If they’re well enough to undergo combination
chemotherapy, then I’ll probably drop the Erlotinib and do the combination chemotherapy. If they
aren’t well enough, then we’re looking at single agent chemotherapy. I usually keep them on the
Tarceva and add the single agent chemotherapy. But there is not clear right nor wrong here.
Certainly trying to find a clinical trial for this particular patient would be very important and I do try
and look for that. If we don’t have something, I look for that elsewhere. That would be something
very important for patients to talk with their doctors to see if there’s anything locally within an hour
or two hours that they could participate in to try and move this field forward.
Dr. West:
Because I think the only consensus we have is that we just don’t know about what to do. It’s
tough. You get a great response and then that slips away. We all want to get the genie back in
the bottle but haven’t found a way to do that. Do you currently request a rebiopsy of tissue after a
patient develops acquired resistance? And if so, how do you use that information?
Dr. Brahmer:
So routinely, I haven’t in the past. But as we’re learning more and more, some peoples tumors do
change or other tumors are more evident and become more aggressive. I think trying to rebiopsy,
if it’s safe for the patient, would be helpful to try and figure out what type of resistance has
developed. Or if the tumor basically we’ve killed off all the non small cell lung cancer. Now are
we left with something else? Some of the investigators have demonstrated that some of the
patients do develop small cell. So, patients can have mixed tumors that don’t develop into small
cell, but actually that’s what’s left and becomes the primary dominant problem. So I think doing
some biopsy once resistance is required to document what exactly that is would be important.
Dr. Heather Wakelee, Stanford University Cancer Center, Palo Alto, CA:
So, I tend to keep people on as long as I can until, to me, there’s no question of growth and no
question that the growth is relatively rapid. Though if someone, the nodules have grown by a few
millimeters and a few months more there’s a few more millimeters, but there’s not jump. Once
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there’s more growth or a new site, I will go. If someone has never had a platinum doublet, I will
bring in a platinum doublet. Those still work really well on EGFR mutations and can be pretty well
tolerated if someone performance status is still good. So, that’s usually what I will go to next if I
start with first-line EGFR TKI, unless I have a really good trial open for those who have developed
secondary resistance.
Dr. West:
And when you do. . .
Dr. Wakelee:
I stop the erlotinib. I give people a break from it, with the idea that, if the resistance is from the
T790M mutant clone, there’s definitely data that this clone diminished over time also as the EGFR
TKI. And that you can bring back some of the sensitivity if you give patients a break and I’ve
certainly seen that in some patients.
Dr. West:
So, you’ve reintroduced it after an interval and seen a response. Ok. You don’t add anything to
the Tarceva like Avastin or something like that. You just switch over to what you wonder consider
first-line?
Dr. Wakelee:
No, I don’t. We’re developing a study that’s looking at an FGF, VEGF inhibitor. I know many
people are doing similar things, but if I didn’t start with the Avastin, I don’t think that there’s any
convincing data that adding it to the Erlotinib or Tarceva will necessarily bring back a response. It
might delay resistance that we developed and we see a prolongation of disease-free survival in
those studies. But, nothing that I’ve seen that if you’re already on it and progressing and you add
in a VEGF inhibitor then that you get a benefit again.
Dr. West:
And you don’t have much enthusiasm for increasing the dose?
Dr. Wakelee:
So I have in patients who develop CNS disease, particularly leptin and gherlin. Where I know that
my chemo is not as likely to benefit, I have, on some of those patients, given them high-dose,
pulse dosing, but I haven’t had success with that yet. It’s something the Memorial people are
doing more. If it’s something with a EGFR that I started on a small dose, because they were a
small person and I knew they had a mutation, I have sometimes gone up to the 150. But that
might give you a little more time on the drug, but it’s not going to give you a drastic impact.
Dr. West:
Do you currently request a re-biopsy of a tissue after a patient develops a resistance to an EGFR
TKI?
Page 8 of 10
Dr. Wakelee:
Only on trial. It’s something that we’re looking and starting to do more. We didn’t have the
capacity to do the necessary or the interesting testing like looking for T790M. So it wasn’t going
to change what I was going to do to help the patient, except those trial. But, we are going to start
doing that more.
Dr. West:
In the patients who you have done it, do you have a lot of difficulty with insurance coverage,
things like that?
Dr. Wakelee:
It’s only on trial, so I haven’t outside of trial.
Dr. Karen Reckamp, City of Hope Cancer Center, Duarte, CA
So we see plenty of these patients, especially being in Southern California with our patient
demographic. So we see this is a very common scenario. I think there are multiple issues in this
and I think that now that we are giving Erlotinib or Tarceva as first line therapy for patients with
EGFR mutation it’s different in my thought process when someone progresses is very different
than when we were giving it as a second or third line because there was really not a whole lot left
when someone was getting second or third line. Whereas we do have viable therapies for
patients when they have had it as first line. And what we often see, because Tarceva is a
sitostatic drug, often patients slowly start to progress. I try to take it by symptoms.
I try not to take it by specific rhesus because often this tumor has shrank to almost nothing so by
rhesus, 20% could be even ½ a centimeter growth. So try to take it by symptoms and once they’re
in the progression stage, I tend to do scans kind of on the two month basis because usually I’ll
spread that out a little bit longer when they’re responding and not having any symptoms. So kind
of giving them a two month window of scans, watch it incredibly closely and try and keep them on
the Tarceva because I think they’re still benefitting. I think what’s happening is that they have
probably two lines of cells, some that are coming resistant and some that are still sensitive.
Again, when patients were getting it as second line, taking that away I think was incredibly
detrimental because, again there is not a lot left that’s going to help their tumor.
Patients who are getting it as first line, still have chemotherapy as a viable treatment option. I
think chemotherapy works incredibly well without the Tarceva. And I’m not exactly sure how to
pair it with the Tarceva and it’s definitely more difficult to give with the Tarceva. So, again, before
when we were giving it in third line, I did often continue the Tarceva and then start with something
else. But now that I’m giving it in the first line, when I do decide to start something else, I tend to
give chemotherapy alone and they tend to do incredibly well with the chemotherapy too.
Dr. West:
So you haven’t seen too much of a problem with the rebound effect of stopping it in the face of
some progression when you decide it’s enough progression and they get remarkably worse?
Dr. Reckamp:
Not in the first line. In the second and third line, definitely. Not in the first line and that’s why,
chemo all of a sudden their tumor is growing again and they have this great very positive time. So
it’s an incredibly different disease to treat now that we’re treating it with Erlotinib in the first line.
Obviously I’d like to get a biopsy done to understand this tumor a little better and as we’ve started
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to hear, if you rebiopsy over time, the tumor even changes over time. So if they get a break with
chemo, they may be able to go back to another type of EGFR inhibitor or even back to Tarceva
again.
Dr. West:
You anticipated one of my questions. How enthusiastically do you recommend a re-biopsy and
how do patients respond to this? Are there practical barriers such as their own concerns about
safety, reimbursement and what are you going to do with the information you have?
Dr. Reckamp:
So I think that I’m more and more an advocate of getting additionally biopsies partially because
we have clinical trials available now that are specific for specific types of tumor and so for many
people there will be a specific answer and even if we don’t have a clinical trial, there may be one
in the country and if they have a specific mutation, for many patients it may be worthwhile,
especially for EGFR mutant patients.
So I think re-biopsying, especially in an EGFR mutant where we know what happens after and we
have some potential options even if they are under investigation I think it’s worthwhile. Patients,
once they understand, again you’re talking about an EGFR mutant lung cancer patient. So, this is
a person who understands that they can greatly benefit from knowing the molecular make up of
their tumor. Most of these patients are on board. And even if there is some financial burden, it’s
usually in the hundreds of dollars and their co payments for treatments could be much more than
that. So if it means that they can go on to a potential clinical trial or find something else, they’re
incredibly motivated.
Dr. West:
How often do you go back to the EGFR inhibitor from first line after some interval on chemo and
off of an EGFR inhibitor entirely?
Dr. Reckamp:
So, I have to say that, fortunately, this is so relatively new that we’ve been using it in first line. I
think that most of the patients that start it in the first line are still in the chemo part and not
progressed after chemo. So most patients haven’t. but I wouldn’t hesitate. I think that it would be
a great time as first line, second line and potentially what we’re trying to do again is put them on
the second generation inhibitors or other types of clinical trials. But I wouldn’t hesistate to put
someone back on Tarceva.
Dr. West:
I have had patients who are on first line progressed, go on chemo, various things for years and
have had impressive responses the second time around, not usually as long lived.
Dr. Reckamp:
Right. And most of them are quite happy to be off of Tarceva for a period of time. Once you’re
giving even first line chemo it seems like a break to them once they’re not on the chronic toxicities
of Tarceva. So I think there is some reason to stop it and again, as we’re seeing, the biopsy
changed potentially the biology is changing and you want those sensitive tumor cells to grow back
again and you may be able to have better responses
Dr. West:
I hope that the program was helpful, and we’d also like to again thank the folks from LUNGevity
Foundation for their partnership on this program. Thank you.
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