Recent Treatment Advances in Small Cell Lung Cancer

August 23, 2021

Information

August 22, 2021

Yale Cancer Center

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00:00Funding for Yale Cancer Answers
00:02is provided by Smilow Cancer
00:04Hospital and AstraZeneca.
00:08Welcome to Yale Cancer Answers with
00:10your host, doctor Anees Chagpar.
00:12Yale Cancer Answers features
00:13the latest information on cancer
00:16care by welcoming oncologists and
00:18specialists who are on the forefront of
00:20the battle to fight cancer. This week,
00:22it's a conversation about lung
00:24cancer with Doctor Anne Chiang.
00:25Doctor Chiang is an associate professor
00:28in medical oncology at the Yale School
00:31of Medicine where Doctor Chagpar is
00:33a professor of surgical oncology.
00:36Let's start at the beginning.
00:38I think a lot of
00:41people know about lung cancer,
00:43but this whole differentiation
00:44between small cell, non small cell
00:47tell us a little bit more about that.
00:49What exactly is the difference?
00:51How many people are affected by each?
00:54And why should we care?
00:56I think that the basics about
00:59lung cancer are that they form in the lung.
01:02There's mainly two different types,
01:04small cell, that underneath the microscope
01:06the pathologist looks at the cells and
01:09they're very small and round and blue,
01:12and everything else which is non small cell.
01:14The small cell kind is typically
01:16a little bit more aggressive.
01:18It grows more quickly.
01:20It tends to spread.
01:21There are different types that I typically
01:23tell my patients are like chocolate,
01:26vanilla and pistachio.
01:27There is adenocarcinoma,
01:29squamous cell carcinoma,
01:30and other types,
01:31and they really are simply
01:34different types that act a little bit differenlty.
01:37They look a little bit different
01:40underneath the microscope,
01:42and sometimes there are molecular
01:44markers that can help us to understand
01:47a particular subtype that might
01:50be responsive to taking a pill,
01:53for example, instead of IV medication.
01:57Of all of these types the first
02:00question is which type are
02:02the most common.
02:07You say the small cells are a little bit
02:10more aggressive than the non small
02:12cells and even within that there's
02:14a whole bunch of different types.
02:17What type is most common?
02:20What's the distribution
02:21in terms of these cancers?
02:23The most common type is
02:26non small cell and pretty much
02:2880-85% of lung cancer
02:30is non small cell and then
02:3215-20% is small cell
02:35and so we know that smoking
02:38is related to lung cancer,
02:40but are there specific risk factors for
02:43getting each of these different types,
02:46or is it kind of all just a mishmash
02:50and which type you get is luck of the draw?
02:54Smoking is definitely a risk factor for
02:57both non small cell and small cell.
03:00That being said, there are folks who
03:03are never smokers, a small population
03:05of never smokers or light smokers
03:08who may develop mutations in specific
03:12genes called EGFR or ALK ROS1.
03:19Some of these mutations are
03:22called oncogenes and these mutations
03:27tend to lead to lung cancer.
03:30A specific kind and because it's
03:33not sort of the same as the lung
03:37cancer that comes from smoking where
03:40repeated exposure and inflammation to
03:43carcinogens caused lung cancer,
03:48those patients with, for example,
03:50a mutation in EGFR can actually be treated
03:53with a targeted therapy that targets EGFR,
03:56and that, as I said before,
03:59is often in the shape of a
04:02pill that you can take daily.
04:04So it's really important when
04:07you're diagnosed with lung cancer
04:10to understand the pathology and
04:12specifically the molecular pathology.
04:13That means the kinds of mutations
04:16that might be available.
04:18Especially if
04:19you've never smoked,
04:21or if you have a very light history
04:23or remote history of smoking
04:26For the people who have never smoked or
04:29have a very light history of smoking,
04:32are they more likely to get one
04:34type of lung cancer in terms of small
04:37cell versus non small cell than others?
04:40And these mutations that
04:41you're talking about,
04:42are they more common in small
04:44cell or non small cell or does it
04:47make a difference at all?
04:49So these mutations that I spoke
04:51of are more common in non small
04:53cell and those folks who are light
04:56or never smokers are more likely
04:58to develop non small cell lung
05:01cancer than small cell lung cancer.
05:03Typically it has rarely happened
05:06that I've seen patients who never
05:08smoked develop small cell cancer,
05:10but typically there is a history
05:12of smoking.
05:14You mentioned earlier that
05:15small cell were more aggressive.
05:17Tell us about the prognosis.
05:19So it sounds to me like if you're going
05:22to have a choice you would prefer to
05:25have a non small cell lung cancer.
05:28But how bad is one versus the other?
05:33I think that the key thing to
05:35know for both is that there have
05:37really been a lot of advances such
05:40that we've actually seen improvements
05:42in the outcomes for both non small
05:45cell and small cell.
05:48And this was just published last year
05:50in the New England Journal of Medicine
05:53that the incidence of both
05:56these and the outcomes of both
05:59these types of cancers are improving.
06:01So I think that's a
06:03really important message to know.
06:07The other aspect of how
06:09you're going to do
06:11with this particular cancer
06:13has to do with staging,
06:15and that just means the geography
06:17of where the cancer is in your body
06:20when when you're diagnosed with it.
06:25If you have tumors that are just
06:27in the lung or have migrated
06:30into very nearby lymph nodes,
06:32then you maybe have a stage one
06:34or stage two cancer.
06:37You may be eligible for a local
06:39treatment like surgery or radiation
06:41in combination with chemotherapy to
06:43really try to remove that tumor,
06:46and that's when you have the best prognosis,
06:49regardless if it's non
06:51small cell or small cell.
06:53Overall, folks with non small cell
06:56do little bit better. But again,
06:59having lung cancer,
07:01it's definitely a treatable disease.
07:03If you have stage four cancer,
07:05which means that you've had disease
07:08that has traveled outside of the
07:10lung to a different organ such as
07:13the liver or the brain or your bones,
07:15then we take a different approach,
07:18which is then we need to use
07:21systemic therapy.
07:21That means something that gets
07:24into your bloodstream because every
07:26single cancer cell anywhere needs to
07:28have a blood supply and therefore
07:30administering chemotherapy,
07:31or more recently,
07:33all these advances in immunotherapy
07:37through the blood into the bloodstream,
07:41that way those therapeutic
07:43drugs can reach all of the cancer
07:46cells that are in your body,
07:48wherever they may be.
07:51Well, it's certainly good news
07:53that lung cancer,
07:54which is something that I think a
07:57lot of people fear, is becoming
07:59a treatable disease and that
08:01there are all of these advances
08:03and I want to get into that.
08:05But first something that you said really
08:08struck a chord with me and has been
08:10the case with a lot of cancers and that is
08:13the earlier you find it,
08:15the lower the stage,
08:17the more treatable it is.
08:18So if you have a stage one lung cancer that's
08:22more treatable than a stage four lung cancer,
08:25and I was wondering if you could talk a
08:28little bit about advances that have
08:30been made in terms of screening
08:33that have helped us to find these
08:35lung cancers earlier?
08:38Screening is a hot topic now because
08:40the US Preventive Services
08:43Task Force just issued a different
08:45recommendation or it altered their
08:48recommendation on screening for lung cancer.
08:51So previously, if you were aged 55 or older,
08:54or if you had a 30 pack year history
08:58of smoking and that means smoking one
09:01pack per day for roughly 30 years,
09:04then you would be eligible for a low dose
09:09CT scan because you had a higher
09:12risk of lung cancer
09:16and being able to have a screening CT
09:19scan allows us to pick up
09:21things when they're very small and
09:24you don't have any symptoms and often
09:27help us to detect lung cancers when
09:30they are in a very early stage.
09:32So recently in March
09:36the US Preventive Services Task
09:38Force changed that recommendation
09:40to drop the age to 50 and for
09:43the pack year history to 20.
09:46So the idea being, let's expand the
09:49population of people that are being screened.
09:54I think that our insurers
09:56are catching up with that but
10:00the recommendations
10:02have changed and I think that that's
10:05going to be very positive in terms
10:08of again being able to detect
10:11lung cancers in earlier stages where they
10:14might be able to undergo local therapy
10:17such as surgery or focused radiation.
10:21So important for people to
10:23get screened because there are so
10:26many advances in terms of treatment.
10:28Just one clarifying question though,
10:30and the other thing that
10:33a lot of people have now done,
10:36especially because we've seen
10:38advances in things like smoking
10:41cessation is to quit smoking.
10:43So let's suppose that you have a 20-25
10:46or thirty pack year history of smoking,
10:49but you just quit.
10:50You made it a New Year's
10:54resolution and you quit maybe a year ago,
10:57maybe six months ago.
10:58Are you still eligible for screening?
11:01Should you still be screened even
11:03though now you're officially a
11:05non smoker or a former smoker?
11:07Yes, if you have a history of
11:09smoking that's 25 pack years,
11:11even if it was ten years ago,
11:14you can still be eligible
11:15for this screening.
11:17I think it's a really important
11:20message to folks that
11:22wherever you are in your course of
11:27stopping smoking and it's certainly
11:29one of the hardest things to do,
11:31it's always important to realize that
11:34stopping or quitting smoking is going
11:36to help you and help your lungs.
11:38It's going to help your overall
11:42health and you're going to do
11:44better than if you continue to smoke.
11:51There is data that even for folks who
11:54have smoked a lot over the course
11:56and maybe even 2 packs per day.
11:59We certainly had
12:01in our society a number of years
12:03where everybody smoked and that
12:05was really sort of run of the mill,
12:08that was a very common thing,
12:10so I think that it's really
12:13important that wherever you are,
12:14if you're a
12:16one pack a day smoker, 2 pack a day
12:22or you smoke a couple of cigarettes a week,
12:25I think that stopping smoking
12:28can really help you and we do have a
12:31smoking cessation clinic here at Yale
12:33that's incredibly successful.
12:35There have been so many advances that
12:38I can't even keep track.
12:40It was just the patch and the lozenge.
12:43And now there's so many different
12:46options to help people stop and
12:48and being able to do some of this
12:50through Televisit consultation
12:52either through video or phone,
12:57can allow people to access this
12:59kind of help and support
13:02to really improve their health,
13:04It is important to quit smoking and talk
13:06to your doctor or call a quit
13:09line to get the help you need.
13:11We're going to take a short
13:12break for a medical minute.
13:14Please stay tuned to learn more about
13:16small cell lung cancer with my guest
13:18Doctor Anne Chiang.
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13:28Learn more at astrazeneca-us.com.
13:32It's estimated that over 240,000
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13:38with over 3000 new cases being
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13:42one in eight American men will
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13:46the course of his lifetime.
13:47Major advances in the detection
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13:53number of men who die from the
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13:59office using two simple tests.
14:01A physical exam and a blood test.
14:04Clinical trials are currently underway
14:07at federally designated Comprehensive
14:09cancer centers such as Yale Cancer
14:11Center and Smilow Cancer Hospital,
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14:19More information is available at
14:22yalecancercenter.org. You're listening
14:24to Connecticut Public Radio.
14:26Welcome
14:26back to Yale Cancer Answers.
14:28This is doctor Anees Chagpar and I'm
14:31joined tonight by my guest Doctor Anne Chiang.
14:33We're discussing recent treatment
14:35advances in small cell lung cancer
14:38and right before the break you
14:40were telling us about the fact that
14:42there have been really exciting
14:44advances both in small cell as well
14:46as in non small cell lung cancer
14:49that have really affected outcomes
14:51for patients with these diseases.
14:53So tell us more about some
14:56of these exciting advances.
14:58I'd love to. This is a really exciting
15:00time for lung cancer.
15:02I remember back to when I started at Yale,
15:06which was almost 10 years ago,
15:08and I put my first patient or one of my first
15:12patients on a clinical trial and at that time
15:15the standard of care was chemotherapy,
15:18and in this case we were looking at treating
15:21this patient with immunotherapy
15:23and not doing chemotherapy first.
15:26And he did extremely well.
15:28And in fact, I saw him a couple of
15:31weeks ago and he has been off trial
15:34with no treatment for the past eight
15:37years and he is contemplating retirement
15:40and he's doing just incredibly well.
15:44And that still sends shivers down my spine and I
15:48know that it's not every single patient
15:51that has that kind of result.
15:53But I think the more that we can learn
15:56through studying and through biology,
15:59through clinical trials,
16:00our aim is really to do the best for
16:03our patients and push that edge as far
16:05as it can go in terms of how they do.
16:58One of the trials that I'm a national
17:03Investigator on spearheading
17:05is a trial called Insigna
17:08and it's run through our cooperative groups,
17:11that's groups that
17:14help to do research, clinical
17:17research in the communities.
17:19This trial is open at about
17:22850 different centers,
17:23we're looking for 850 patients to
17:27enroll on this trial and we're trying
17:31to understand for PD L1 positive or for
17:35patients who have this marker of
17:38PDL one if they are treated with
17:42either immunotherapy upfront or
17:45immunotherapy combined with chemotherapy,
17:49which group will do better
17:51and then with those patients
17:53who are treated with immunotherapy
17:55alone if they progress,
17:56can we then add chemo to the immunotherapy
17:59to sort of boost the immune system?
18:02And at the same time we're going
18:04to be using the tissue and the
18:06science that we can gather to try to
18:09understand if there are biomarkers or
18:11signatures that can help us understand
18:13which people will benefit and which
18:16people have less of a benefit.
18:18that's a really exciting trial that is ongoing,
18:21we're about 40% of the way through on that,
18:24and I think that you know there are
18:26thousands of
18:29immunotherapy trials in cancer right now,
18:30but I think this is one that
18:33will really help us to understand
18:35what's the right thing to do
18:37up front.
18:40We talk on this show
18:42all the time about immunotherapy.
18:44And it sounds like particularly
18:46giving your anecdotal case with your
18:49patient who's now nine years out,
18:51it sounds like immunotherapy
18:52really does have a role or a
18:55potential role in lung cancer.
18:57With your trial,
18:58is it open to non small cell lung cancer,
19:01small cell lung cancer, or any lung cancer?
19:05So that trial is open for non small cell
19:09lung cancer and it's for patients who have
19:13stage four disease and who have a tumor
19:16that has a positive marker for PDL 1,
19:20which is an important molecule
19:22in the signaling for immunotherapy
19:26in terms of small cell lung cancer,
19:30we have a number of clinical
19:32trials also that are available,
19:35and I think that the story for
19:39small cell is that chemo plus immunotherapy
19:44has been
19:48approved in
19:50the past couple of years.
19:52That's how the landscape
19:54of small cell has changed.
19:56It was just previously treated with
19:58chemotherapy and just in the past couple
20:01of years we now treat with chemo,
20:04plus immunotherapy.
20:04And then the question is what happens after?
20:07If that doesn't work anymore?
20:09And I think we have a number of different
20:13clinical trials that are available for that,
20:16and we're trying to really
20:18understand the biology behind
20:20why people respond or why they
20:23don't respond and in small cell it's
20:26typically a tumor where there's
20:28less tissue available to test,
20:31and so we've put together
20:33a really great team here for
20:35studying the science that includes
20:39PhD scientists working
20:41on lung cancer as well as myself.
20:44And, you know,
20:45I think it would be too hard to go into
20:49all of the details here,
20:52but I think we're going to learn
20:55a lot about how we can explore the
20:58biology of small cell in order
21:00to find out vulnerabilities in
21:03order to target this disease.
21:05It sounds like you
21:07know, across the board in lung cancer,
21:10whether you've got small cell or
21:12whether you've got non small cell.
21:15It sounds like immunotherapy is increasingly
21:18becoming part of the arsenal that your
21:20doctor may use to treat your disease.
21:23And that really has made a
21:26difference now, and is that the case
21:29only for people who express PDL one?
21:32We've talked on this show before
21:35about checkpoint inhibitors like PDL one.
21:38So is it the case that people who
21:40present with metastatic lung cancer,
21:42stage four, that they should be having
21:46their tumors checked for that marker
21:48and then treated with immunotherapy
21:50or is immunotherapy something that
21:53your doctor may use regardless?
21:57For non small cell lung cancer you
22:01definitely need to have your tumor checked.
22:04If you have high levels of PDL
22:07one so greater than 50% then you
22:10may be eligible to be treated
22:13with just immunotherapy alone.
22:15Otherwise you really need to be
22:18treated with a combination of chemo
22:21and immunotherapy. For small cell, it is different.
22:25There's very little PDL one
22:26expression to start with and
22:29for the trials that have been done,
22:33they've looked at all comers
22:37so it doesn't matter if you have PDL one
22:40expression or not because it's so low anyway,
22:42but all of the small cell patients
22:44that are diagnosed are treated
22:46with chemo plus immuno.
22:48It is interesting how that kind
22:51of plays out between the
22:54two disease types.
22:56So tell us a little bit more about other
23:00advances that have occurred?
23:02Before the break you were telling us
23:06about an alphabet soup of markers,
23:08things like EGFR and others.
23:11ALK, for example.
23:12How have these really changed the landscape?
23:16Are oncologists
23:18using them to kind of target their
23:21therapies to personalize things as it were?
23:27Great question. So as I was
23:29talking about before the break,
23:31if you for example have an EGFR
23:34mutation which EGFR stands for
23:36epidermal growth factor receptor,
23:38I think that the key is that
23:41what we found over the years is
23:43that if you have a mutation in
23:46that you really respond to
23:49taking that EGFR directed therapy.
23:53In this case,
23:54it's a drug called osimertinib
23:59and you should do that off the bat
24:02if you have stage four disease.
24:04If you have stage one disease or
24:06stage two disease or you've had or
24:09stage three that you've had surgery,
24:11there has been a very new advance in
24:14the past year and it was
24:17led by Doctor Roy Herbst of Yale,
24:20our team that basically
24:22says that after you
24:24have that surgery,
24:25you benefit from taking that oral therapy.
24:32And I think it's important also
24:34to mention that these trials,
24:36such as the ADURO trial,
24:38were offered not only in
24:40our main academic campus,
24:43in New Haven,
24:44but also in all of our Smilow
24:46care centers across the state.
24:48And we have 15 of them,
24:51so we've been able to
24:54allow patients who are in
24:57all parts of the state participate
25:00in these types of clinical
25:02trials that can really,
25:04really give access to cutting
25:06edge drugs or to help to advance
25:09science for all patients.
25:11And that's the case across the
25:14country, that many of these
25:17large trials are offered at
25:19academic centers that are offered at
25:22community centers and that really people
25:25should talk to their doctor because
25:28trials, whether they were led by
25:29Yale or led by investigators at
25:32other centers are often available
25:34for patients across the nation.
25:35Isn't that right?
25:36Absolutely, and I think
25:38that you know, in the past clinical
25:40trials you though, Gee,
25:42I will try a clinical trial if everything
25:45else has failed and it's not working for me,
25:48so I'm going to try something experimental.
25:50Now that paradigm is completely shifted,
25:52so it may be that you have your
25:55first treatment that you're
25:56going on a clinical trial.
25:58And it really is to try and
26:00better the outcomes for each of
26:03the recommended treatments
26:05that are recommended approaches,
26:07standard approaches so that we can
26:09push the envelope and
26:12really do the best for our patients.
26:16And in terms of these targeted therapies,
26:18whether it's a
26:21drug that's targeting an EGFR,
26:23whether it's a drug targeting ALK or
26:26whatever, this is across the board.
26:28Is that right between small
26:30cell and non small cell?
26:32And so the question that I have is if
26:35that is the case then for everyone
26:38who has lung cancer it sounds like
26:41they should have their tumor profiled
26:43with regards to all of these
26:46mutations so that their doctor can
26:48better inform what might be the
26:51therapy that works best for them.
26:53Is that right?
26:54So the the mutations that
26:56I talked about EGFR and so forth are
26:59really much more common in non small cells.
27:02So we do as a matter of fact test all
27:05of our non small cell samples
27:08and look for
27:11these mutations. For small
27:13cell it's a little bit different.
27:16We don't have typically
27:20mutations in EGFR or ALK,
27:22specifically for small cell.
27:24However, because we still think
27:26that it's important to test for
27:29those and typically not up front,
27:32in other words, when you're first diagnosed,
27:35but if you are treated with
27:38chemo and immunotherapy,
27:39and perhaps it typically works very
27:42well in 80 to 90% of the cases
27:46you have a very good response
27:50but that disease may come back when
27:53you have stage four disease,
27:55it's typically not something that you're
27:58going to cure because you
28:00don't have the option of cutting out
28:02or radiating every microscopic cell.
28:04So if the disease regrows,
28:06if and when,
28:08unfortunately,
28:08the disease regrows,
28:09we want to have options and
28:12really develop more tools is
28:13what I tell my patients to be
28:16able to manage their disease,
28:18and that's why we
28:20do work so much with clinical
28:23trials and feel that that's
28:25incredibly important to be able to
28:28advance outcomes for our patients.
28:30Doctor Ann Chiang
28:31is an associate professor and medical
28:33oncologist at the Yale School of Medicine.
28:36If you have questions,
28:37the address is cancer answers at
28:39yale.edu and past editions of the
28:41program are available in audio and
28:44written form at yalecancercenter.org.
28:46We hope you'll join us next week to learn
28:49more about the fight against cancer.
28:52Here on Connecticut public radio.
28:53Funding for Yale Cancer Answers
28:56is provided by Smilow Cancer
28:58Hospital and AstraZeneca.