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INFORMATION FOR

Advances in Lung Cancer

March 29, 2021
  • 00:00Support for Yale Cancer Answers
  • 00:02comes from AstraZeneca, dedicated
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  • 00:14Welcome to Yale Cancer
  • 00:16Answers with your host,
  • 00:17Doctor Anees Chagpar. Yale Cancer Answers
  • 00:20features the latest information on
  • 00:22cancer care by welcoming oncologists and
  • 00:24specialists who are on the forefront of
  • 00:26the battle to fight cancer. This week,
  • 00:28it's a conversation about lung
  • 00:30cancer with Doctor Roy Herbst.
  • 00:32Doctor Herbst is
  • 00:33Ensign Professor of Medicine
  • 00:34and medical Oncology,
  • 00:35an professor of pharmacology at
  • 00:37the Yale School of Medicine,
  • 00:39where Doctor Chagpar is a
  • 00:42professor of surgical oncology.
  • 00:44Maybe we can start off by talking
  • 00:47a little bit about the Epidemiology
  • 00:49of lung cancer, is it still
  • 00:51one of the leading
  • 00:53cancers and the leading
  • 00:55cause of cancer related death?
  • 00:57Lung cancer still is
  • 00:59unfortunately the number one cause of cancer
  • 01:02death worldwide with maybe 1.6, 1.7
  • 01:04deaths a year by incidence.
  • 01:06It's not the number one cancer diagnosed
  • 01:09more breast cancer is diagnosed in women,
  • 01:12and prostate cancer in men,
  • 01:13but by death, it certainly is the major
  • 01:16killer because it tends to present in
  • 01:19a metastatic way, already having spread.
  • 01:21But you know, we're making great inroads
  • 01:24now with early screening for lung cancer
  • 01:26and hopefully will find it earlier.
  • 01:29And we have seen improvements in
  • 01:31survival but there is still work to do.
  • 01:33I wanted to start off there and
  • 01:36certainly will get into some of the recent
  • 01:38advances in screening and treatment.
  • 01:41But you know, lung cancer used to be
  • 01:43the number one cancer, and we saw that
  • 01:46breast cancer and prostate cancer kind
  • 01:49of pulled ahead several years ago.
  • 01:52And in part, I think that that was
  • 01:54related to some advances that were
  • 01:57made in terms of lung cancer.
  • 01:59Primary prevention.
  • 02:00In other words,
  • 02:01not getting lung cancer to begin with.
  • 02:04Do you want to kind of talk
  • 02:07about some of that?
  • 02:08Particularly where it
  • 02:10pertains to smoking cessation?
  • 02:12Right, the best way to
  • 02:15treat lung cancer still is to prevent it,
  • 02:18and certainly even though there
  • 02:19is a very real group of patients
  • 02:22with a non smoking lung cancer,
  • 02:24as many as 15% or more of patients in the
  • 02:27United States about double that in Asia,
  • 02:30still smoking is one of the primary
  • 02:33reasons for causation and lung cancer.
  • 02:35So major efforts have been underway over
  • 02:37the last 50-60 years in the United States
  • 02:40since the initial Surgeon General's report
  • 02:42to stem the tide of smoking.
  • 02:45We've gone down from 50% of Americans
  • 02:48smoking, perhaps to less than 20%,
  • 02:50maybe 18% or so,
  • 02:51differing among different groups
  • 02:53in different states,
  • 02:54but we still need to do better.
  • 02:56But smoking clearly is a cause and now we
  • 02:59worry as we've really worked on smoking
  • 03:02both with education and
  • 03:04with medications, with counseling.
  • 03:05Now we see this big surge in E-
  • 03:08cigarette use and we worry and I'm
  • 03:10very involved with the American
  • 03:12Association of Cancer Research, actually.
  • 03:15The task force on tobacco control.
  • 03:17We're actually looking very carefully
  • 03:19at E-cigarettes because we worry
  • 03:21that these are being used now by
  • 03:23children and young adults
  • 03:25and they're filled with nicotine,
  • 03:26and nicotine is the addictive
  • 03:28substance in cigarettes,
  • 03:29so people are getting addicted to nicotine.
  • 03:31And then they go to what's
  • 03:33called dual use and start to use
  • 03:35combustible cigarettes, the
  • 03:37type we're most familiar with.
  • 03:38And then of course
  • 03:40the story is all too familiar,
  • 03:42and this is important
  • 03:45to tell you here in New Haven where we live
  • 03:48the rates are probably a
  • 03:50bit higher than the national average
  • 03:53and we're doing a lot of work
  • 03:56with community programs
  • 03:58as part of our long funded research
  • 04:01through the National Cancer Institute,
  • 04:03we just completed a large trial when
  • 04:06patients came into the hospital,
  • 04:08some with problems, some for screening.
  • 04:10We tried to use new methods to help them
  • 04:13to stop smoking, new messaging tools,
  • 04:16so that's still such an important part
  • 04:18of this field to not smoke also we have
  • 04:21to worry about other risk factors.
  • 04:24Asbestos,
  • 04:25radon gas is something we all
  • 04:27think about here
  • 04:28living in Connecticut,
  • 04:29all these things can be a risk
  • 04:31factor for future development of this
  • 04:34disease. So I want to pick up on a couple
  • 04:37of things that you said just quickly.
  • 04:39So the first was your study looking
  • 04:42at new messaging techniques.
  • 04:47Roughly 20% of the population smoke
  • 04:50and for many of them it is
  • 04:53very difficult to quit.
  • 04:55There are all kinds of things out there.
  • 04:58There's quitlines,
  • 04:59there's patches, there's gum,
  • 05:00there's behavioral modification.
  • 05:01Some people even advocate
  • 05:03paying people to quit smoking,
  • 05:05and some people are even suggesting
  • 05:08that E cigarettes can be used as a
  • 05:11bridge to help people to quit smoking.
  • 05:13So for our listeners out there,
  • 05:16the 20% who may be smoking
  • 05:19as they listen to this,
  • 05:21what's the best way to quit and
  • 05:23where can they get help?
  • 05:24Well, first of all,
  • 05:25I would definitely ask for help.
  • 05:27That could be your physician.
  • 05:29That could be a nurse practitioner.
  • 05:30Just whoever you see for
  • 05:32your regular health checks.
  • 05:33Some of these quit lines
  • 05:34can be extremely helpful,
  • 05:36and there are a number of
  • 05:37ways to work on quitting,
  • 05:39and now this is an addiction
  • 05:40and it is hard to quit,
  • 05:42especially if you've been using
  • 05:44cigarettes for a long time.
  • 05:45The nicotine is really hard to beat,
  • 05:47so there are a couple of ways to do it
  • 05:50here in our smoking cessation clinic,
  • 05:52they will assess each person
  • 05:54on an individual basis.
  • 05:55There are certainly ways to substitute
  • 05:57for the nicotine other than a
  • 05:59combustible cigarette that you smoke.
  • 06:02There are certain medications that can help,
  • 06:05but then of course,
  • 06:06behavioral modification and counseling,
  • 06:07which I think is so important here at Yale,
  • 06:10where we have an amazing center of
  • 06:12emotional intelligence and there
  • 06:14have been studies done to show
  • 06:16that different types of messaging
  • 06:17can be more effective than others.
  • 06:19For example,
  • 06:20many of you have seen
  • 06:22cigarette cartoons.
  • 06:23Not so much in the United States,
  • 06:25but around the world where there
  • 06:27are these horrible images of people
  • 06:28and the consequences of smoking.
  • 06:30Those are very negative type messages,
  • 06:32but they're intended to scare
  • 06:33people from not smoking.
  • 06:34There's been some thought that more
  • 06:36gain framed messaging where you
  • 06:38might show well if you don't smoke,
  • 06:40you'll feel better if you don't smoke,
  • 06:42your skin will look better.
  • 06:43That could be another way of doing it.
  • 06:45We're testing some of those
  • 06:47new methods here at Yale.
  • 06:48The other thing we've done
  • 06:49is a biofeedback approach,
  • 06:50so we actually have an infrared
  • 06:53device that can measure carotenoids
  • 06:54in the skin and the health of the
  • 06:57skin which we know actually can
  • 06:59get somewhat destroyed with tobacco
  • 07:01use and we actually are using that
  • 07:03sort of biofeedback with patients to
  • 07:05try to maintain them from using tobacco.
  • 07:08So we've been working very hard on this.
  • 07:10Lisa Fucito leads this effort now
  • 07:12in our clinic and we're trying to
  • 07:15serve as many patients as possible.
  • 07:17And by the way,
  • 07:18it's not just lung cancer.
  • 07:20About 20 different cancers that
  • 07:22all can trace their
  • 07:23origin back to smoking and
  • 07:25we are really trying to work on this.
  • 07:27It's something that's now as
  • 07:28part of our medical record.
  • 07:30Everyone's asked the question
  • 07:31about tobacco use.
  • 07:32And primary prevention is just so important,
  • 07:34but even if someone has smoked
  • 07:36and many people have and they
  • 07:37stopped they are still at risk
  • 07:39of developing lung
  • 07:40cancer and this is where screening
  • 07:42comes in and the idea
  • 07:44that you can do a low dose CAT
  • 07:47scan to screen for lung cancer.
  • 07:48And I'm very proud to say that
  • 07:50even during this very difficult
  • 07:52year with covid and clinics
  • 07:53closed or moved,
  • 07:54we've actually had a very strong
  • 07:56year number wise in the
  • 07:58number of patients in the
  • 08:00area that we've screened.
  • 08:06So screening patients and
  • 08:07finding cancers early in people
  • 08:09at high risk is also a very
  • 08:11important tool that we're using.
  • 08:14I think the last question
  • 08:16before we move on from smoking
  • 08:19cessation is I wanted to get
  • 08:20your thoughts on taxation.
  • 08:22So certainly in
  • 08:23some parts of the world they've
  • 08:26found that making
  • 08:28it hurt in people's pocketbooks
  • 08:31is often a deterrent to smoking.
  • 08:34Where do you come down on that?
  • 08:38Do you advocate that governments
  • 08:40should put stiff taxes on cigarette
  • 08:42purchases to make that less appealing?
  • 08:46Well, that a
  • 08:48tough one. You know,
  • 08:49different states do different things.
  • 08:51I still remember once being in a drug
  • 08:53store in New York City and someone
  • 08:55came in for a pack of cigarettes.
  • 08:58And it could cost up to $15-20
  • 09:00with some of the different taxes and
  • 09:04I think people will find the cigarettes
  • 09:07elsewhere.
  • 09:09I think it's a useful technique but it would have
  • 09:11to be a universal sort of technique.
  • 09:13Otherwise people will find
  • 09:15ways of getting cigarettes.
  • 09:16I'm much more
  • 09:17in favor of
  • 09:18some of the approaches I mentioned,
  • 09:20whether it be counseling, medications.
  • 09:24I think that the E cigarettes as
  • 09:25a substitute for someone who's
  • 09:27tried everything else could
  • 09:28work in that way,
  • 09:30but it has to be studied in a regulated way.
  • 09:33You know there needs to be a clinical
  • 09:35trial and we're actually trying to do
  • 09:37some of those here right now at Yale,
  • 09:40especially now with some of the
  • 09:41covid regulations.
  • 09:42But it would be nice to see if we can
  • 09:45use these cigarettes in a measured way.
  • 09:47With a prescribed dose,
  • 09:48as a tool, but
  • 09:52there are other forms of
  • 09:54nicotine replacement,
  • 09:54but clearly stopping people from
  • 09:56smoking whatever method is used
  • 10:00because it's a National emergency
  • 10:02despite the fact that it's
  • 10:04so much better than it was
  • 10:06Really the only good level of
  • 10:08tobacco use is none.
  • 10:11And you worry also about the E cigarettes
  • 10:14being yet another addictive substance
  • 10:16and we don't really know long term what
  • 10:19the health consequences are of that.
  • 10:21The other thing that you mentioned was that
  • 10:24there are many lung cancers that happen
  • 10:27for reasons outside of cigarette smoking.
  • 10:30For example, you mentioned in Asia
  • 10:33about 50% of lung cancers are
  • 10:35not related to cigarette smoking,
  • 10:38and I wonder whether you think
  • 10:40that there are some environmental
  • 10:43issues that we need to consider.
  • 10:46I mean is this part of
  • 10:49the pollution that
  • 10:51we're seeing in terms of
  • 10:56manufacturing and so on that might be
  • 10:58greater in some industrialized parts
  • 11:00of Asia that promotes lung cancer.
  • 11:03Or do we not know why there's these
  • 11:07disparities?
  • 11:09We're talking about the non smoking lung
  • 11:11cancer which initially was due to
  • 11:14the epidermal growth factor receptor
  • 11:16mutation that was discovered more
  • 11:18than 20 years ago and those levels are
  • 11:21much higher in Asia than in the US.
  • 11:24About double. 30 to 40% versus 15 to 20%.
  • 11:28I don't know that it's environment
  • 11:29because if someone is born in
  • 11:31Asia and moves to Southern California,
  • 11:33it seems like they have the same higher risk.
  • 11:36So I think there's something genetic
  • 11:39which amazes me with all the
  • 11:41tools we have now to sequence
  • 11:43genomes and we can sequence
  • 11:46dozens and dozens of patients each day.
  • 11:48We still have not found what
  • 11:50the link there is.
  • 11:52What is the genetic factor?
  • 11:53It's being looked at quite intensively.
  • 11:55It's this cooperation between
  • 11:57researchers around the world.
  • 11:58But we still don't know exactly
  • 12:00why these mutations in epidermal
  • 12:02growth factor receptor are so much
  • 12:03more common in Asia than the US,
  • 12:05but we're looking for it and
  • 12:08learning how to treat that type of
  • 12:10cancer with oral agents.
  • 12:12It's actually been historic.
  • 12:13I think that's part of the
  • 12:15reason we're seeing
  • 12:16a couple percent a year decreases in the
  • 12:19death rates from lung cancer because
  • 12:20of what we call targeted therapy.
  • 12:22But even when those drugs work,
  • 12:24as you know, patients will become resistant.
  • 12:27That's actually something we're
  • 12:28studying very much here in our group. NOTE Confidence: 0.8304425
  • 12:30Katie Politi and Sarah Goldberg
  • 12:32and Mark Lemon actually is one
  • 12:35of the projects on our big lung
  • 12:37Spore Grant looking
  • 12:38at mechanisms of sensitivity and
  • 12:40resistance to these drugs so that
  • 12:42we can help more patients develop
  • 12:44newer and better,
  • 12:45more effective and
  • 12:46less toxic ways to treat this disease.
  • 12:49Yeah, and as
  • 12:52we kind of think about lung
  • 12:54cancer and the fact that it no
  • 12:56longer is the number one cancer
  • 12:58in people thanks to reduction in
  • 13:00smoking cessation and other things,
  • 13:02it still remains the number one
  • 13:05killer in terms of being the number
  • 13:08one cause of cancer related morbidity
  • 13:10and mortality. Has that reduced in
  • 13:13recent years thanks to some of the
  • 13:15things that we'll be talking about in
  • 13:18terms of understanding the genomics
  • 13:20and tailored therapy and so on.
  • 13:22Are we seeing the needle move?
  • 13:24Oh absolutely, and I've seen this myself,
  • 13:27so I started working in this field
  • 13:30about 20-25 years ago as a young fellow
  • 13:33at Dana
  • 13:35Farber Cancer Institute actually,
  • 13:36and no one even wanted to work in this field.
  • 13:40Back then, it was really a death sentence
  • 13:41if you had lung cancer,
  • 13:44we had surgery and radiation techniques,
  • 13:46but if it had spread
  • 13:48the chemotherapy was OK,
  • 13:49but really didn't do much.
  • 13:51And I think over the years
  • 13:53we've really taken the five year
  • 13:55overall survival for lung cancer,
  • 13:56which was in the low teens 10-11%.
  • 13:59And now it's as high as 19% or more.
  • 14:02Now that's all across all stages,
  • 14:04stage 1,2,3 and four.
  • 14:06Four being the most advanced,
  • 14:07but that's progress.
  • 14:08But the real progress that we're
  • 14:10seeing is identifying a more
  • 14:12personalized approach to this disease
  • 14:14and learning how to treat it with
  • 14:16some of these new targeted therapies.
  • 14:18Learning how to treat it with immunotherapy.
  • 14:20And yeah,
  • 14:21I've seen
  • 14:23patients now in 2021
  • 14:26who now
  • 14:30come here to our clinics
  • 14:33and they either get standard
  • 14:34of care or clinical trials.
  • 14:36And a smaller proportion increasing
  • 14:37every day are doing better,
  • 14:39so there is definitely progress
  • 14:41visible progress in this field.
  • 14:42And understanding the science,
  • 14:46what drives the lung cancer,
  • 14:48what's causing it to grow and how
  • 14:50to treat it in more effective ways.
  • 14:53We're going to talk all about
  • 14:55that right after we take a short
  • 14:57break for a medical minute.
  • 14:58Please stay tuned to learn
  • 15:00more with my guest. Doctor
  • 15:02Roy Herbst. Support for Yale Cancer
  • 15:04Answers comes from AstraZeneca working
  • 15:06to eliminate cancer as a cause of death.
  • 15:08Learnmore@astrazeneca-us.com. This
  • 15:14is a medical minute about genetic
  • 15:17testing which can be useful for
  • 15:19people with certain types of cancer
  • 15:22that seem to run in their families.
  • 15:24Patients that are considered at risk
  • 15:27receive genetic counseling and testing so
  • 15:29informed medical decisions can be based
  • 15:32on their own personal risk assessment.
  • 15:34Resources for genetic counseling and
  • 15:36testing are available at federally
  • 15:38designated comprehensive cancer centers.
  • 15:40Interdisciplinary teams include geneticists,
  • 15:42genetic counselors, physicians,
  • 15:43and nurses
  • 15:44who work together to provide
  • 15:46risk assessment and steps to prevent
  • 15:49the development of cancer.
  • 15:50More information is available
  • 15:52at yalecancercenter.org.
  • 15:53You're listening to Connecticut Public Radio.
  • 15:57Welcome back to Yale Cancer Answers.
  • 16:00This is doctor Anees Chagpar and I'm
  • 16:03joined tonight by my guest Doctor Roy Herbst.
  • 16:06We're talking about recent advances in the
  • 16:09management of lung cancer patients and Roy,
  • 16:12right before the break you were telling
  • 16:14us that you have seen visible progress in
  • 16:18terms of reducing lung cancer mortality.
  • 16:20This remains the number one cancer
  • 16:23killer of Americans, both men and women,
  • 16:26but we're seeing progress.
  • 16:28So there are so many different avenues
  • 16:30that we've seen in terms of lung cancer
  • 16:34management that have contributed to this.
  • 16:36What do you think is the greatest
  • 16:39driver?
  • 16:42The ACS announced earlier this year a 2% decrease
  • 16:45in deaths from lung cancer since 2013.
  • 16:48So clearly something's happening.
  • 16:49I think part of it is the prevention,
  • 16:53either primary prevention by avoiding
  • 16:55smoking and other toxins, or the screening.
  • 16:58But I have to believe a lot of
  • 17:00it's been the therapies that we've
  • 17:02seen in the last several years.
  • 17:05Understanding the molecular
  • 17:06basis of this disease.
  • 17:10That's not really true.
  • 17:13Everyone's cancer is a little bit different,
  • 17:15caused by a different mechanism,
  • 17:17a different genetic background.
  • 17:18So now what we're doing is we're
  • 17:21taking the patients cancer and we're
  • 17:23performing molecular techniques
  • 17:24for sequencing.
  • 17:24We're looking at what makes it tick now.
  • 17:27What is driving that cancer?
  • 17:29And now there are about seven or
  • 17:31eight different different mutations,
  • 17:32different markers that we
  • 17:34can then pair with a specific drug.
  • 17:36So we're personalizing the therapy,
  • 17:38and that's nice
  • 17:39because these are oral therapies,
  • 17:40that you take by mouth and are
  • 17:43much less toxic than the
  • 17:45chemotherapy we used to use,
  • 17:46and we see the tumors shrink in
  • 17:48a large percentage of patients.
  • 17:50So many of these started
  • 17:51out as clinical trials,
  • 17:53and now they're moving
  • 17:54forward to standard of care.
  • 17:55So I think that's having a great benefit.
  • 17:58I've seen it myself.
  • 17:59Over the last 15-20 years,
  • 18:00certainly within the last decade,
  • 18:02many approved drugs in this space,
  • 18:04so you really want to make sure
  • 18:06that your cancer is analyzed in
  • 18:07this way so that you have access
  • 18:09to these drugs now.
  • 18:11Like everything else,
  • 18:12nothing is perfect with time
  • 18:13the tumor will get smart and learn
  • 18:15how to override these blockages.
  • 18:17But that's why we're doing research.
  • 18:19All of us that are at different
  • 18:21centers to try to figure out
  • 18:22one of the next steps and,
  • 18:24and we're continuing to raise the bar,
  • 18:26but that's certainly been
  • 18:27one of the major advances.
  • 18:29The second has been immunotherapy,
  • 18:31and the idea that we can
  • 18:33use the body's own immune system
  • 18:34to attack the cancer really began
  • 18:37in Melanoma and kidney cancer.
  • 18:38But lung cancer being so common,
  • 18:40we're seeing just amazing
  • 18:42results that we can now actually
  • 18:44take a cancer that's already spread
  • 18:46throughout the body and we can treat
  • 18:49with one of these immunotherapy drugs.
  • 18:50And we're doing that now.
  • 18:52And when we do that,
  • 18:54actually in about 20% of
  • 18:56the patients we see
  • 18:57amazing results and the rest
  • 18:58sometimes we see some
  • 19:00activity and others we don't,
  • 19:02so we have to do a little bit more,
  • 19:04but these are patients who never
  • 19:06before would have had any hope of
  • 19:08doing well on some of these therapies.
  • 19:10And then if that all was not enough,
  • 19:12we're taking all these therapies
  • 19:14that work in the most advanced
  • 19:15stages and we're moving them
  • 19:17earlier and earlier in disease.
  • 19:19I can tell you one
  • 19:20thing that I've seen
  • 19:21over my career is the best drugs
  • 19:23work best when they are used in the
  • 19:26earliest possible stage after surgery,
  • 19:27when the burden of lung cancer is the lowest.
  • 19:30So now we're doing what's
  • 19:32called adjuvent therapy,
  • 19:33and I was very fortunate to actually
  • 19:35present last year
  • 19:37some data where an EGFR inhibitor used
  • 19:39after surgery had really high impact
  • 19:41on how patients did after that surgery,
  • 19:44so the sky is the limit.
  • 19:46Research in this area is paying off.
  • 19:48We're seeing tangible benefits,
  • 19:49but when I could also say and tell you,
  • 19:52I'm sure many listening to this
  • 19:54notice from their own experience,
  • 19:56we still have to do even better,
  • 19:58and that's why research, science,
  • 20:00operative work working together
  • 20:02is going to be so important,
  • 20:04and that's the type of programs that
  • 20:06we lead here at our center.
  • 20:08Roy, let's dig into a few things
  • 20:11that you talked about.
  • 20:13So the first was targeted
  • 20:15therapy and Genomics,
  • 20:16and we've talked a lot on this show
  • 20:19about kind of unpacking that concept
  • 20:22in a variety of different cancers.
  • 20:24and really trying to figure out what
  • 20:27are the main drivers in lung cancer,
  • 20:30so are all lung cancers kind
  • 20:33of profiled in this way?
  • 20:35And are there particular mutations that
  • 20:37have druggable targets that you look for?
  • 20:41Well, certainly all lung cancers
  • 20:43when they've already spread
  • 20:44from the lungs are what we
  • 20:46call non squamous lung cancers,
  • 20:48which the majority should
  • 20:49be profiled in this way.
  • 20:51And actually it's my belief we actually
  • 20:53should probably profile all of them
  • 20:55to understand one of the
  • 20:57determinants that are causing that
  • 20:59cancer to grow because that will allow
  • 21:01us to match with the best therapy.
  • 21:03Now I'm concerned you know one
  • 21:05of the big issues we have is
  • 21:07access to care and making sure all
  • 21:09patients get this screening done.
  • 21:11One thing we're doing a lot
  • 21:14of work on is to try to get navigators
  • 21:17out to all the different areas of the city
  • 21:20to build trust.
  • 21:22Within Connecticut we want every patient
  • 21:24to have access to coming to a center
  • 21:27where they can have their tumor profiled.
  • 21:29But yes,
  • 21:30if you profile the tumor,
  • 21:31there's probably as much as a
  • 21:3320% chance you'll find something
  • 21:35that will allow you to match
  • 21:37that patient with an oral drug,
  • 21:39which in my opinion is certainly preferable
  • 21:40to giving a nonspecific chemotherapy,
  • 21:43so that's a huge advance.
  • 21:44And we're continuing to find more of
  • 21:46these and new combinations that can be used.
  • 21:49So yes,
  • 21:50that's what we call precision guided
  • 21:52therapy and for the patients who
  • 21:54don't have one of these mutations,
  • 21:57do they get standard chemotherapy
  • 21:59and have there been any advances
  • 22:01in terms of standard chemotherapy
  • 22:04for those people who either don't
  • 22:06have a druggable target or who have
  • 22:09a druggable target, and who recur?
  • 22:11Well, incredibly, the
  • 22:12answer is yes.
  • 22:13So I mentioned immunotherapy already.
  • 22:15So if someone does not
  • 22:17have one of those targets,
  • 22:19we actually can look for another target,
  • 22:22something called PDL1,
  • 22:23now PDL1 actually was in part
  • 22:26discovered by Lieping Chen, NOTE Confidence: 0.80644786
  • 22:28a professor here at Yale,
  • 22:30and he's one of our collaborators,
  • 22:32but we actually can measure
  • 22:34PDL one and tumors.
  • 22:35And if the level is very high,
  • 22:37that tells us that the
  • 22:39immunotherapy might work alone.
  • 22:40So we give those patients immunotherapy,
  • 22:43assuming they don't have
  • 22:44some reason we can't.
  • 22:45Sometimes you can't reactivate the
  • 22:47immune system because someone might
  • 22:49already have some bad arthritis or
  • 22:51know what we call an autoimmune
  • 22:53disease that precludes that.
  • 22:54But for the rest of these, again,
  • 22:56unless they have a contraindication,
  • 22:58we're giving immunotherapy in
  • 22:59combination with chemotherapy.
  • 23:00Would have been what I would have
  • 23:03guessed would have been such an active
  • 23:05therapy, but for whatever reason,
  • 23:07when you give chemotherapy
  • 23:08and immunotherapy together,
  • 23:09you at least have an additive effect,
  • 23:11meaning the chemotherapy kills
  • 23:13some of the tumor cells,
  • 23:14releases some of the proteins
  • 23:16that activate the immune system,
  • 23:18and then use these drugs that
  • 23:19we call a checkpoint
  • 23:21inhibitor that unleash the power
  • 23:23of the immune system and that's
  • 23:25become a standard of therapy.
  • 23:26Now I'll tell you that
  • 23:28those results are really
  • 23:30good and much better than
  • 23:32what we've had in the past.
  • 23:33But in my opinion we still
  • 23:35have to raise the bar,
  • 23:37so that's where clinical trials come in,
  • 23:39and it would be my my big hope that
  • 23:41in that room when a patient and a
  • 23:44physician or nurse practitioner or
  • 23:45whoever is there are meeting. someone
  • 23:48brings up, is there a clinical trial?
  • 23:50Is there something new that's
  • 23:52looking at a new agent?
  • 23:53A new drug,
  • 23:54something that might even be more active?
  • 23:56And of course,
  • 23:57that's investigation,
  • 23:58but that's really how we
  • 24:00continue to do better and better,
  • 24:03and we're inching up the
  • 24:06benefits from therapy in lung cancer.
  • 24:11So certainly clinical trials.
  • 24:13I mean, we've talked on this show a
  • 24:16lot about clinical trials and the
  • 24:18fact that people who participate
  • 24:20in clinical trials tend to do
  • 24:22better than people who don't.
  • 24:24Are all of the clinical trials in
  • 24:27lung cancer now really geared around
  • 24:29targeted therapies and immunooncology
  • 24:32or are there any clinical trials that
  • 24:35are looking at advances in standard
  • 24:38chemotherapy for people who may not
  • 24:40be eligible for those other therapies?
  • 24:43Either because they don't have a
  • 24:46target or because they don't have
  • 24:49a tumor that's expressing PDL 1.
  • 24:52Well, standard chemotherapy
  • 24:53clearly has its place,
  • 24:55and certainly in earlier stages of
  • 24:57disease before the tumors have spread
  • 24:59from the lung we're using chemotherapy
  • 25:01with radiation therapy, for example,
  • 25:03and that can be curative therapy.
  • 25:05We often add immunotherapy in afterwards,
  • 25:08but I actually personally think
  • 25:09we've pretty much come as far
  • 25:12as we can with chemotherapy.
  • 25:14It's somewhat nonspecific.
  • 25:15It can have a number of side effects.
  • 25:18However, we're finding new
  • 25:19targets like right now,
  • 25:21just in the last several months,
  • 25:23there's been data on a new target
  • 25:26against something called Kras.
  • 25:28Now Kras, which is an oncogene,
  • 25:30actually first came from a rat model.
  • 25:34Kras actually is about
  • 25:3612 to 20% of lung tumors.
  • 25:38The actual variant of this that
  • 25:40now has multiple drugs that are
  • 25:42out there is what we call G12C.
  • 25:45Probably doesn't mean much to a
  • 25:47lot of those who are listening,
  • 25:49but it's a specific abnormality that
  • 25:52occurs in 12% of lung cancer patients.
  • 25:54That's a lot of patients.
  • 25:56Remember,
  • 25:56I told you it's 1.6, 1.7
  • 25:58worldwide and there are actually agents now,
  • 26:00not approved yet,
  • 26:01but that are in clinical trials
  • 26:03showing positive results that
  • 26:04can make those tumors shrink.
  • 26:06So before I pull off some chemotherapy,
  • 26:08which by the way we will do and
  • 26:09we do need to use and sometimes we
  • 26:12even use it as we're waiting for a
  • 26:14clinical trial to become available.
  • 26:16We are beginning to study and
  • 26:18use these Kras drugs,
  • 26:19and I think that's going
  • 26:21to be the next paradigm.
  • 26:22So we've gone from chemotherapy
  • 26:24to targeted therapy,
  • 26:24to immunotherapy, and now Kras
  • 26:26which is another target.
  • 26:27But it's a broad target
  • 26:29and it always was
  • 26:30the Holy Grail,
  • 26:32there's been so many
  • 26:34approaches and ways to try to target it.
  • 26:36It's a very difficult target for
  • 26:38a cancer because I don't want
  • 26:40to get into too much detail here,
  • 26:42but just to say that the pocket that
  • 26:44we have to block with a drug is so
  • 26:47narrow that it's very hard to get a
  • 26:49drug in there to block that.
  • 26:52But scientists and chemists have
  • 26:53figured that out. Another example of
  • 26:55science drives innovation,
  • 26:56science brings new agents to the clinic.
  • 26:58Then we test them in the clinic
  • 27:00and we test them using samples
  • 27:03from patients and a series of
  • 27:05very careful studies to bring new
  • 27:08new things to standard of care.
  • 27:10So amazing progress but
  • 27:12more that needs to
  • 27:13happen. And this brings me
  • 27:15to the whole area of clinical trials.
  • 27:18For many patients historically
  • 27:20they always thought that clinical trials
  • 27:22were what you tried when there was nothing
  • 27:25else left when you had exhausted all
  • 27:28other options when the cancer was metastatic NOTE Confidence: 0.856393
  • 27:31and had spread all over the body,
  • 27:34but you're really talking about
  • 27:36clinical trials as being
  • 27:40state of the art medicine and
  • 27:43that might actually be helpful,
  • 27:45particularly in patients who are so
  • 27:47fortunate as to have detected their
  • 27:49cancer early when it's not metastatic.
  • 27:52Can you talk a little bit more about that?
  • 27:59Clinical trials really are
  • 28:03the best way and in many cases
  • 28:06to you know, treating cancer,
  • 28:08especially when you're dealing with
  • 28:11a situation where you know it is
  • 28:14incurable and you're not able to
  • 28:16treat with the standard of care,
  • 28:18I still remember the example of the
  • 28:21patient, has to be about 8 years ago,
  • 28:23we were studying a drug in clinical trial,
  • 28:26one of these immune checkpoint inhibitors
  • 28:28and he came in with advanced lung cancer.
  • 28:30He had already been to see several
  • 28:33other practitioners around
  • 28:35the state and we had one slot left
  • 28:37in this trial and you know we went
  • 28:39back and forth and he decided to
  • 28:41go on this study and he went on
  • 28:44this drug that is now approved and
  • 28:46did very well.
  • 28:47Eight years later,
  • 28:48I still get emails from him.
  • 28:50He's a photographer.
  • 28:51He sends me pictures from the wild.
  • 28:53This is where a clinical trial
  • 28:55can really pay off now,
  • 28:57because now many years before
  • 28:58approval of a drug,
  • 28:59someone took a chance on this trial
  • 29:01that the alternative would have
  • 29:03been standard of care therapy.
  • 29:04So we're not keeping anything
  • 29:06from this patient,
  • 29:07but bring that trial to bear
  • 29:09on that patient really helped him
  • 29:11and helped him live a quality life.
  • 29:13So that's what we hope for.
  • 29:15That's why clinical trials are so important.
  • 29:17And now I think, as you're alluding to,
  • 29:19we're using these clinical trials
  • 29:21in the earliest stages of disease,
  • 29:22so I know you're a surgeon,
  • 29:24so you cut out tumors,
  • 29:26but still there's a chance it will recur
  • 29:29even if you've gotten everything out.
  • 29:30So now what we're doing is we're taking
  • 29:33these best therapies in lung cancer,
  • 29:36the immunotherapy that targeted therapy
  • 29:38when using them after surgery even
  • 29:40when we see that there's no disease.
  • 29:41Knowing that these are high risk
  • 29:43of recurrence and those data,
  • 29:45some of them are already showing
  • 29:48positive results so
  • 29:49the field of research and clinical
  • 29:51care are one and the bottom line
  • 29:53is we want to give the best
  • 29:55care for patients at the best
  • 29:57possible time.
  • 29:59Dr. Roy Herbst is Ensign Professor of Medicine in Medical Oncology
  • 30:00and professor of Pharmacology
  • 30:03at the Yale School of Medicine.
  • 30:05If you have questions,
  • 30:06the address is canceranswers@yale.edu
  • 30:08and past editions of the program
  • 30:10are available in audio and written
  • 30:12form at yalecancercenter.org.
  • 30:14We hope you'll join us next week to
  • 30:16learn more about the fight against
  • 30:19cancer here on Connecticut Public Radio.