Advances in Lung Cancer

Transcript

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00:14 --> 00:15Welcome to Yale Cancer
00:15 --> 00:17Answers with your host,
00:17 --> 00:19Doctor Anees Chagpar. Yale Cancer Answers
00:19 --> 00:21features the latest information on
00:21 --> 00:23cancer care by welcoming oncologists and
00:23 --> 00:26specialists who are on the forefront of
00:26 --> 00:28the battle to fight cancer. This week,
00:28 --> 00:30it's a conversation about lung
00:30 --> 00:32cancer with Doctor Roy Herbst.
00:32 --> 00:32Doctor Herbst is
00:32 --> 00:34Ensign Professor of Medicine
00:34 --> 00:35and medical Oncology,
00:35 --> 00:37an professor of pharmacology at
00:37 --> 00:38the Yale School of Medicine,
00:38 --> 00:41where Doctor Chagpar is a
00:41 --> 00:43professor of surgical oncology.
00:44 --> 00:46Maybe we can start off by talking
00:46 --> 00:48a little bit about the Epidemiology
00:48 --> 00:51of lung cancer, is it still
00:51 --> 00:52one of the leading
00:52 --> 00:54cancers and the leading
00:54 --> 00:56cause of cancer related death?
00:57 --> 00:59Lung cancer still is
00:59 --> 01:01unfortunately the number one cause of cancer
01:01 --> 01:04death worldwide with maybe 1.6, 1.7
01:04 --> 01:06deaths a year by incidence.
01:06 --> 01:09It's not the number one cancer diagnosed
01:09 --> 01:11more breast cancer is diagnosed in women,
01:11 --> 01:13and prostate cancer in men,
01:13 --> 01:16but by death, it certainly is the major
01:16 --> 01:18killer because it tends to present in
01:18 --> 01:21a metastatic way, already having spread.
01:21 --> 01:23But you know, we're making great inroads
01:23 --> 01:26now with early screening for lung cancer
01:26 --> 01:28and hopefully will find it earlier.
01:28 --> 01:30And we have seen improvements in
01:30 --> 01:32survival but there is still work to do.
01:32 --> 01:35I wanted to start off there and
01:35 --> 01:38certainly will get into some of the recent
01:38 --> 01:40advances in screening and treatment.
01:40 --> 01:43But you know, lung cancer used to be
01:43 --> 01:46the number one cancer, and we saw that
01:46 --> 01:48breast cancer and prostate cancer kind
01:49 --> 01:51of pulled ahead several years ago.
01:51 --> 01:54And in part, I think that that was
01:54 --> 01:56related to some advances that were
01:56 --> 01:59made in terms of lung cancer.
01:59 --> 02:00Primary prevention.
02:00 --> 02:01In other words,
02:01 --> 02:03not getting lung cancer to begin with.
02:03 --> 02:06Do you want to kind of talk
02:06 --> 02:08about some of that?
02:08 --> 02:09Particularly where it
02:09 --> 02:11pertains to smoking cessation?
02:12 --> 02:14Right, the best way to
02:14 --> 02:17treat lung cancer still is to prevent it,
02:17 --> 02:19and certainly even though there
02:19 --> 02:21is a very real group of patients
02:21 --> 02:23with a non smoking lung cancer,
02:23 --> 02:26as many as 15% or more of patients in the
02:27 --> 02:29United States about double that in Asia,
02:29 --> 02:32still smoking is one of the primary
02:32 --> 02:34reasons for causation and lung cancer.
02:34 --> 02:37So major efforts have been underway over
02:37 --> 02:39the last 50-60 years in the United States
02:39 --> 02:42since the initial Surgeon General's report
02:42 --> 02:45to stem the tide of smoking.
02:45 --> 02:47We've gone down from 50% of Americans
02:47 --> 02:50smoking, perhaps to less than 20%,
02:50 --> 02:51maybe 18% or so,
02:51 --> 02:52differing among different groups
02:52 --> 02:54in different states,
02:54 --> 02:56but we still need to do better.
02:56 --> 02:59But smoking clearly is a cause and now we
02:59 --> 03:02worry as we've really worked on smoking
03:02 --> 03:04both with education and
03:04 --> 03:05with medications, with counseling.
03:05 --> 03:07Now we see this big surge in E-
03:07 --> 03:10cigarette use and we worry and I'm
03:10 --> 03:12very involved with the American
03:12 --> 03:14Association of Cancer Research, actually.
03:14 --> 03:16The task force on tobacco control.
03:16 --> 03:18We're actually looking very carefully
03:18 --> 03:20at E-cigarettes because we worry
03:20 --> 03:22that these are being used now by
03:22 --> 03:24children and young adults
03:24 --> 03:26and they're filled with nicotine,
03:26 --> 03:27and nicotine is the addictive
03:27 --> 03:29substance in cigarettes,
03:29 --> 03:31so people are getting addicted to nicotine.
03:31 --> 03:33And then they go to what's
03:33 --> 03:35called dual use and start to use
03:35 --> 03:36combustible cigarettes, the
03:36 --> 03:38type we're most familiar with.
03:38 --> 03:40And then of course
03:40 --> 03:42the story is all too familiar,
03:42 --> 03:44and this is important
03:44 --> 03:47to tell you here in New Haven where we live
03:47 --> 03:50the rates are probably a
03:50 --> 03:52bit higher than the national average
03:52 --> 03:55and we're doing a lot of work
03:55 --> 03:57with community programs
03:57 --> 04:00as part of our long funded research
04:00 --> 04:03through the National Cancer Institute,
04:03 --> 04:05we just completed a large trial when
04:05 --> 04:07patients came into the hospital,
04:07 --> 04:09some with problems, some for screening.
04:09 --> 04:12We tried to use new methods to help them
04:12 --> 04:15to stop smoking, new messaging tools,
04:15 --> 04:18so that's still such an important part
04:18 --> 04:21of this field to not smoke also we have
04:21 --> 04:23to worry about other risk factors.
04:23 --> 04:24Asbestos,
04:24 --> 04:26radon gas is something we all
04:26 --> 04:27think about here
04:27 --> 04:28living in Connecticut,
04:28 --> 04:31all these things can be a risk
04:31 --> 04:33factor for future development of this
04:33 --> 04:36disease. So I want to pick up on a couple
04:36 --> 04:39of things that you said just quickly.
04:39 --> 04:41So the first was your study looking
04:41 --> 04:43at new messaging techniques.
04:47 --> 04:50Roughly 20% of the population smoke
04:50 --> 04:52and for many of them it is
04:52 --> 04:54very difficult to quit.
04:54 --> 04:57There are all kinds of things out there.
04:57 --> 04:58There's quitlines,
04:58 --> 05:00there's patches, there's gum,
05:00 --> 05:01there's behavioral modification.
05:01 --> 05:02Some people even advocate
05:02 --> 05:04paying people to quit smoking,
05:04 --> 05:07and some people are even suggesting
05:07 --> 05:10that E cigarettes can be used as a
05:10 --> 05:13bridge to help people to quit smoking.
05:13 --> 05:15So for our listeners out there,
05:15 --> 05:18the 20% who may be smoking
05:18 --> 05:20as they listen to this,
05:20 --> 05:22what's the best way to quit and
05:22 --> 05:24where can they get help?
05:24 --> 05:25Well, first of all,
05:25 --> 05:27I would definitely ask for help.
05:27 --> 05:28That could be your physician.
05:28 --> 05:30That could be a nurse practitioner.
05:30 --> 05:31Just whoever you see for
05:31 --> 05:32your regular health checks.
05:32 --> 05:34Some of these quit lines
05:34 --> 05:35can be extremely helpful,
05:35 --> 05:37and there are a number of
05:37 --> 05:38ways to work on quitting,
05:38 --> 05:40and now this is an addiction
05:40 --> 05:42and it is hard to quit,
05:42 --> 05:43especially if you've been using
05:43 --> 05:45cigarettes for a long time.
05:45 --> 05:47The nicotine is really hard to beat,
05:47 --> 05:49so there are a couple of ways to do it
05:49 --> 05:51here in our smoking cessation clinic,
05:51 --> 05:53they will assess each person
05:53 --> 05:54on an individual basis.
05:54 --> 05:56There are certainly ways to substitute
05:56 --> 05:58for the nicotine other than a
05:58 --> 06:00combustible cigarette that you smoke.
06:02 --> 06:04There are certain medications that can help,
06:04 --> 06:05but then of course,
06:05 --> 06:07behavioral modification and counseling,
06:07 --> 06:10which I think is so important here at Yale,
06:10 --> 06:12where we have an amazing center of
06:12 --> 06:13emotional intelligence and there
06:13 --> 06:15have been studies done to show
06:15 --> 06:17that different types of messaging
06:17 --> 06:19can be more effective than others.
06:19 --> 06:19For example,
06:19 --> 06:22many of you have seen
06:22 --> 06:23cigarette cartoons.
06:23 --> 06:25Not so much in the United States,
06:25 --> 06:26but around the world where there
06:26 --> 06:28are these horrible images of people
06:28 --> 06:29and the consequences of smoking.
06:29 --> 06:31Those are very negative type messages,
06:31 --> 06:32but they're intended to scare
06:32 --> 06:34people from not smoking.
06:34 --> 06:35There's been some thought that more
06:35 --> 06:37gain framed messaging where you
06:37 --> 06:39might show well if you don't smoke,
06:39 --> 06:41you'll feel better if you don't smoke,
06:41 --> 06:42your skin will look better.
06:42 --> 06:45That could be another way of doing it.
06:45 --> 06:46We're testing some of those
06:46 --> 06:47new methods here at Yale.
06:47 --> 06:49The other thing we've done
06:49 --> 06:50is a biofeedback approach,
06:50 --> 06:52so we actually have an infrared
06:52 --> 06:54device that can measure carotenoids
06:54 --> 06:56in the skin and the health of the
06:56 --> 06:59skin which we know actually can
06:59 --> 07:00get somewhat destroyed with tobacco
07:00 --> 07:03use and we actually are using that
07:03 --> 07:05sort of biofeedback with patients to
07:05 --> 07:07try to maintain them from using tobacco.
07:07 --> 07:10So we've been working very hard on this.
07:10 --> 07:12Lisa Fucito leads this effort now
07:12 --> 07:14in our clinic and we're trying to
07:14 --> 07:16serve as many patients as possible.
07:16 --> 07:18And by the way,
07:18 --> 07:19it's not just lung cancer.
07:19 --> 07:21About 20 different cancers that
07:21 --> 07:23all can trace their
07:23 --> 07:24origin back to smoking and
07:24 --> 07:26we are really trying to work on this.
07:26 --> 07:28It's something that's now as
07:28 --> 07:29part of our medical record.
07:29 --> 07:30Everyone's asked the question
07:30 --> 07:31about tobacco use.
07:31 --> 07:33And primary prevention is just so important,
07:33 --> 07:35but even if someone has smoked
07:35 --> 07:37and many people have and they
07:37 --> 07:38stopped they are still at risk
07:38 --> 07:40of developing lung
07:40 --> 07:42cancer and this is where screening
07:42 --> 07:44comes in and the idea
07:44 --> 07:46that you can do a low dose CAT
07:46 --> 07:48scan to screen for lung cancer.
07:48 --> 07:49And I'm very proud to say that
07:49 --> 07:51even during this very difficult
07:51 --> 07:53year with covid and clinics
07:53 --> 07:54closed or moved,
07:54 --> 07:56we've actually had a very strong
07:56 --> 07:58year number wise in the
07:58 --> 07:59number of patients in the
07:59 --> 08:01area that we've screened.
08:05 --> 08:07So screening patients and
08:07 --> 08:08finding cancers early in people
08:08 --> 08:10at high risk is also a very
08:10 --> 08:12important tool that we're using.
08:13 --> 08:16I think the last question
08:16 --> 08:18before we move on from smoking
08:18 --> 08:20cessation is I wanted to get
08:20 --> 08:21your thoughts on taxation.
08:21 --> 08:23So certainly in
08:23 --> 08:25some parts of the world they've
08:25 --> 08:28found that making
08:28 --> 08:31it hurt in people's pocketbooks
08:31 --> 08:34is often a deterrent to smoking.
08:34 --> 08:37Where do you come down on that?
08:37 --> 08:39Do you advocate that governments
08:39 --> 08:42should put stiff taxes on cigarette
08:42 --> 08:45purchases to make that less appealing?
08:46 --> 08:47Well, that a
08:47 --> 08:49tough one. You know,
08:49 --> 08:50different states do different things.
08:50 --> 08:53I still remember once being in a drug
08:53 --> 08:55store in New York City and someone
08:55 --> 08:57came in for a pack of cigarettes.
08:57 --> 08:59And it could cost up to $15-20
08:59 --> 09:02with some of the different taxes and
09:04 --> 09:06I think people will find the cigarettes
09:06 --> 09:09elsewhere.
09:09 --> 09:11I think it's a useful technique but it would have
09:11 --> 09:13to be a universal sort of technique.
09:13 --> 09:14Otherwise people will find
09:14 --> 09:15ways of getting cigarettes.
09:15 --> 09:16I'm much more
09:16 --> 09:18in favor of
09:18 --> 09:20some of the approaches I mentioned,
09:20 --> 09:21whether it be counseling, medications.
09:23 --> 09:25I think that the E cigarettes as
09:25 --> 09:26a substitute for someone who's
09:26 --> 09:28tried everything else could
09:28 --> 09:29work in that way,
09:29 --> 09:32but it has to be studied in a regulated way.
09:32 --> 09:34You know there needs to be a clinical
09:34 --> 09:36trial and we're actually trying to do
09:36 --> 09:38some of those here right now at Yale,
09:39 --> 09:41especially now with some of the
09:41 --> 09:42covid regulations.
09:42 --> 09:44But it would be nice to see if we can
09:44 --> 09:47use these cigarettes in a measured way.
09:47 --> 09:48With a prescribed dose,
09:48 --> 09:50as a tool, but
09:51 --> 09:53there are other forms of
09:53 --> 09:54nicotine replacement,
09:54 --> 09:56but clearly stopping people from
09:56 --> 09:58smoking whatever method is used
10:00 --> 10:01because it's a National emergency
10:01 --> 10:03despite the fact that it's
10:03 --> 10:05so much better than it was
10:05 --> 10:08Really the only good level of
10:08 --> 10:10tobacco use is none.
10:10 --> 10:13And you worry also about the E cigarettes
10:13 --> 10:15being yet another addictive substance
10:15 --> 10:18and we don't really know long term what
10:18 --> 10:21the health consequences are of that.
10:21 --> 10:24The other thing that you mentioned was that
10:24 --> 10:27there are many lung cancers that happen
10:27 --> 10:30for reasons outside of cigarette smoking.
10:30 --> 10:32For example, you mentioned in Asia
10:32 --> 10:35about 50% of lung cancers are
10:35 --> 10:37not related to cigarette smoking,
10:37 --> 10:40and I wonder whether you think
10:40 --> 10:42that there are some environmental
10:42 --> 10:45issues that we need to consider.
10:45 --> 10:49I mean is this part of
10:49 --> 10:51the pollution that
10:51 --> 10:53we're seeing in terms of
10:55 --> 10:58manufacturing and so on that might be
10:58 --> 11:00greater in some industrialized parts
11:00 --> 11:03of Asia that promotes lung cancer.
11:03 --> 11:06Or do we not know why there's these
11:06 --> 11:08disparities?
11:08 --> 11:11We're talking about the non smoking lung
11:11 --> 11:13cancer which initially was due to
11:13 --> 11:15the epidermal growth factor receptor
11:15 --> 11:17mutation that was discovered more
11:17 --> 11:20than 20 years ago and those levels are
11:20 --> 11:24much higher in Asia than in the US.
11:24 --> 11:27About double. 30 to 40% versus 15 to 20%.
11:27 --> 11:29I don't know that it's environment
11:29 --> 11:31because if someone is born in
11:31 --> 11:33Asia and moves to Southern California,
11:33 --> 11:36it seems like they have the same higher risk.
11:36 --> 11:38So I think there's something genetic
11:38 --> 11:41which amazes me with all the
11:41 --> 11:43tools we have now to sequence
11:43 --> 11:45genomes and we can sequence
11:45 --> 11:48dozens and dozens of patients each day.
11:48 --> 11:50We still have not found what
11:50 --> 11:51the link there is.
11:51 --> 11:53What is the genetic factor?
11:53 --> 11:55It's being looked at quite intensively.
11:55 --> 11:56It's this cooperation between
11:56 --> 11:58researchers around the world.
11:58 --> 12:00But we still don't know exactly
12:00 --> 12:01why these mutations in epidermal
12:01 --> 12:03growth factor receptor are so much
12:03 --> 12:05more common in Asia than the US,
12:05 --> 12:07but we're looking for it and
12:07 --> 12:09learning how to treat that type of
12:09 --> 12:11cancer with oral agents.
12:11 --> 12:13It's actually been historic.
12:13 --> 12:14I think that's part of the
12:14 --> 12:16reason we're seeing
12:16 --> 12:18a couple percent a year decreases in the
12:18 --> 12:20death rates from lung cancer because
12:20 --> 12:22of what we call targeted therapy.
12:22 --> 12:24But even when those drugs work,
12:24 --> 12:26as you know, patients will become resistant.
12:26 --> 12:27That's actually something we're
12:27 --> 12:29studying very much here in our group. NOTE Confidence: 0.8304425
12:30 --> 12:32Katie Politi and Sarah Goldberg
12:32 --> 12:34and Mark Lemon actually is one
12:34 --> 12:36of the projects on our big lung
12:36 --> 12:38Spore Grant looking
12:38 --> 12:40at mechanisms of sensitivity and
12:40 --> 12:42resistance to these drugs so that
12:42 --> 12:44we can help more patients develop
12:44 --> 12:45newer and better,
12:45 --> 12:46more effective and
12:46 --> 12:48less toxic ways to treat this disease.
12:48 --> 12:51Yeah, and as
12:51 --> 12:53we kind of think about lung
12:53 --> 12:55cancer and the fact that it no
12:55 --> 12:57longer is the number one cancer
12:57 --> 13:00in people thanks to reduction in
13:00 --> 13:02smoking cessation and other things,
13:02 --> 13:04it still remains the number one
13:04 --> 13:07killer in terms of being the number
13:07 --> 13:10one cause of cancer related morbidity
13:10 --> 13:12and mortality. Has that reduced in
13:12 --> 13:15recent years thanks to some of the
13:15 --> 13:17things that we'll be talking about in
13:17 --> 13:19terms of understanding the genomics
13:19 --> 13:22and tailored therapy and so on.
13:22 --> 13:24Are we seeing the needle move?
13:24 --> 13:27Oh absolutely, and I've seen this myself,
13:27 --> 13:30so I started working in this field
13:30 --> 13:33about 20-25 years ago as a young fellow
13:33 --> 13:35at Dana
13:35 --> 13:36Farber Cancer Institute actually,
13:36 --> 13:39and no one even wanted to work in this field.
13:39 --> 13:41Back then, it was really a death sentence
13:41 --> 13:43if you had lung cancer,
13:43 --> 13:45we had surgery and radiation techniques,
13:45 --> 13:47but if it had spread
13:47 --> 13:49the chemotherapy was OK,
13:49 --> 13:50but really didn't do much.
13:50 --> 13:52And I think over the years
13:52 --> 13:54we've really taken the five year
13:54 --> 13:56overall survival for lung cancer,
13:56 --> 13:59which was in the low teens 10-11%.
13:59 --> 14:02And now it's as high as 19% or more.
14:02 --> 14:04Now that's all across all stages,
14:04 --> 14:05stage 1,2,3 and four.
14:05 --> 14:07Four being the most advanced,
14:07 --> 14:08but that's progress.
14:08 --> 14:10But the real progress that we're
14:10 --> 14:12seeing is identifying a more
14:12 --> 14:13personalized approach to this disease
14:13 --> 14:16and learning how to treat it with
14:16 --> 14:17some of these new targeted therapies.
14:17 --> 14:20Learning how to treat it with immunotherapy.
14:20 --> 14:20And yeah,
14:20 --> 14:23I've seen
14:23 --> 14:25patients now in 2021
14:26 --> 14:28who now
14:29 --> 14:32come here to our clinics
14:32 --> 14:34and they either get standard
14:34 --> 14:35of care or clinical trials.
14:35 --> 14:37And a smaller proportion increasing
14:37 --> 14:38every day are doing better,
14:38 --> 14:40so there is definitely progress
14:40 --> 14:42visible progress in this field.
14:42 --> 14:43And understanding the science,
14:46 --> 14:47what drives the lung cancer,
14:47 --> 14:49what's causing it to grow and how
14:49 --> 14:52to treat it in more effective ways.
14:52 --> 14:54We're going to talk all about
14:54 --> 14:56that right after we take a short
14:56 --> 14:58break for a medical minute.
14:58 --> 14:59Please stay tuned to learn
14:59 --> 15:01more with my guest. Doctor
15:01 --> 15:03Roy Herbst. Support for Yale Cancer
15:03 --> 15:05Answers comes from AstraZeneca working
15:05 --> 15:08to eliminate cancer as a cause of death.
15:08 --> 15:14Learnmore@astrazeneca-us.com. This
15:14 --> 15:16is a medical minute about genetic
15:16 --> 15:19testing which can be useful for
15:19 --> 15:21people with certain types of cancer
15:21 --> 15:24that seem to run in their families.
15:24 --> 15:26Patients that are considered at risk
15:26 --> 15:29receive genetic counseling and testing so
15:29 --> 15:31informed medical decisions can be based
15:31 --> 15:34on their own personal risk assessment.
15:34 --> 15:36Resources for genetic counseling and
15:36 --> 15:37testing are available at federally
15:37 --> 15:39designated comprehensive cancer centers.
15:39 --> 15:41Interdisciplinary teams include geneticists,
15:41 --> 15:42genetic counselors, physicians,
15:42 --> 15:43and nurses
15:43 --> 15:46who work together to provide
15:46 --> 15:48risk assessment and steps to prevent
15:48 --> 15:50the development of cancer.
15:50 --> 15:52More information is available
15:52 --> 15:53at yalecancercenter.org.
15:53 --> 15:55You're listening to Connecticut Public Radio.
15:57 --> 15:59Welcome back to Yale Cancer Answers.
15:59 --> 16:02This is doctor Anees Chagpar and I'm
16:02 --> 16:06joined tonight by my guest Doctor Roy Herbst.
16:06 --> 16:09We're talking about recent advances in the
16:09 --> 16:11management of lung cancer patients and Roy,
16:11 --> 16:14right before the break you were telling
16:14 --> 16:17us that you have seen visible progress in
16:17 --> 16:20terms of reducing lung cancer mortality.
16:20 --> 16:22This remains the number one cancer
16:22 --> 16:25killer of Americans, both men and women,
16:25 --> 16:27but we're seeing progress.
16:27 --> 16:30So there are so many different avenues
16:30 --> 16:33that we've seen in terms of lung cancer
16:33 --> 16:36management that have contributed to this.
16:36 --> 16:39What do you think is the greatest
16:39 --> 16:42driver?
16:42 --> 16:44The ACS announced earlier this year a 2% decrease
16:44 --> 16:47in deaths from lung cancer since 2013.
16:47 --> 16:49So clearly something's happening.
16:49 --> 16:52I think part of it is the prevention,
16:52 --> 16:54either primary prevention by avoiding
16:54 --> 16:57smoking and other toxins, or the screening.
16:57 --> 17:00But I have to believe a lot of
17:00 --> 17:02it's been the therapies that we've
17:02 --> 17:04seen in the last several years.
17:04 --> 17:05Understanding the molecular
17:05 --> 17:07basis of this disease.
17:09 --> 17:11That's not really true.
17:12 --> 17:15Everyone's cancer is a little bit different,
17:15 --> 17:16caused by a different mechanism,
17:16 --> 17:18a different genetic background.
17:18 --> 17:20So now what we're doing is we're
17:20 --> 17:22taking the patients cancer and we're
17:22 --> 17:23performing molecular techniques
17:23 --> 17:24for sequencing.
17:24 --> 17:27We're looking at what makes it tick now.
17:27 --> 17:28What is driving that cancer?
17:28 --> 17:30And now there are about seven or
17:30 --> 17:32eight different different mutations,
17:32 --> 17:34different markers that we
17:34 --> 17:36can then pair with a specific drug.
17:36 --> 17:37So we're personalizing the therapy,
17:37 --> 17:38and that's nice
17:38 --> 17:40because these are oral therapies,
17:40 --> 17:43that you take by mouth and are
17:43 --> 17:44much less toxic than the
17:44 --> 17:46chemotherapy we used to use,
17:46 --> 17:48and we see the tumors shrink in
17:48 --> 17:49a large percentage of patients.
17:49 --> 17:51So many of these started
17:51 --> 17:52out as clinical trials,
17:52 --> 17:53and now they're moving
17:53 --> 17:55forward to standard of care.
17:55 --> 17:57So I think that's having a great benefit.
17:57 --> 17:58I've seen it myself.
17:58 --> 18:00Over the last 15-20 years,
18:00 --> 18:01certainly within the last decade,
18:01 --> 18:03many approved drugs in this space,
18:03 --> 18:05so you really want to make sure
18:05 --> 18:07that your cancer is analyzed in
18:07 --> 18:09this way so that you have access
18:09 --> 18:10to these drugs now.
18:10 --> 18:11Like everything else,
18:11 --> 18:13nothing is perfect with time
18:13 --> 18:15the tumor will get smart and learn
18:15 --> 18:16how to override these blockages.
18:16 --> 18:18But that's why we're doing research.
18:18 --> 18:20All of us that are at different
18:20 --> 18:22centers to try to figure out
18:22 --> 18:23one of the next steps and,
18:23 --> 18:25and we're continuing to raise the bar,
18:25 --> 18:27but that's certainly been
18:27 --> 18:28one of the major advances.
18:28 --> 18:30The second has been immunotherapy,
18:30 --> 18:32and the idea that we can
18:32 --> 18:34use the body's own immune system
18:34 --> 18:36to attack the cancer really began
18:36 --> 18:38in Melanoma and kidney cancer.
18:38 --> 18:40But lung cancer being so common,
18:40 --> 18:42we're seeing just amazing
18:42 --> 18:44results that we can now actually
18:44 --> 18:46take a cancer that's already spread
18:46 --> 18:48throughout the body and we can treat
18:48 --> 18:50with one of these immunotherapy drugs.
18:50 --> 18:52And we're doing that now.
18:52 --> 18:53And when we do that,
18:53 --> 18:55actually in about 20% of
18:55 --> 18:56the patients we see
18:56 --> 18:58amazing results and the rest
18:58 --> 19:00sometimes we see some
19:00 --> 19:01activity and others we don't,
19:01 --> 19:04so we have to do a little bit more,
19:04 --> 19:06but these are patients who never
19:06 --> 19:08before would have had any hope of
19:08 --> 19:10doing well on some of these therapies.
19:10 --> 19:12And then if that all was not enough,
19:12 --> 19:13we're taking all these therapies
19:13 --> 19:15that work in the most advanced
19:15 --> 19:16stages and we're moving them
19:16 --> 19:18earlier and earlier in disease.
19:18 --> 19:20I can tell you one
19:20 --> 19:21thing that I've seen
19:21 --> 19:22over my career is the best drugs
19:22 --> 19:25work best when they are used in the
19:25 --> 19:27earliest possible stage after surgery,
19:27 --> 19:30when the burden of lung cancer is the lowest.
19:30 --> 19:31So now we're doing what's
19:31 --> 19:32called adjuvent therapy,
19:32 --> 19:34and I was very fortunate to actually
19:34 --> 19:36present last year
19:36 --> 19:38some data where an EGFR inhibitor used
19:38 --> 19:41after surgery had really high impact
19:41 --> 19:43on how patients did after that surgery,
19:43 --> 19:45so the sky is the limit.
19:45 --> 19:47Research in this area is paying off.
19:47 --> 19:49We're seeing tangible benefits,
19:49 --> 19:52but when I could also say and tell you,
19:52 --> 19:53I'm sure many listening to this
19:53 --> 19:55notice from their own experience,
19:55 --> 19:58we still have to do even better,
19:58 --> 20:00and that's why research, science,
20:00 --> 20:01operative work working together
20:01 --> 20:03is going to be so important,
20:03 --> 20:06and that's the type of programs that
20:06 --> 20:08we lead here at our center.
20:08 --> 20:10Roy, let's dig into a few things
20:10 --> 20:13that you talked about.
20:13 --> 20:14So the first was targeted
20:14 --> 20:15therapy and Genomics,
20:15 --> 20:19and we've talked a lot on this show
20:19 --> 20:21about kind of unpacking that concept
20:21 --> 20:24in a variety of different cancers.
20:24 --> 20:27and really trying to figure out what
20:27 --> 20:30are the main drivers in lung cancer,
20:30 --> 20:32so are all lung cancers kind
20:32 --> 20:34of profiled in this way?
20:34 --> 20:37And are there particular mutations that
20:37 --> 20:39have druggable targets that you look for?
20:41 --> 20:42Well, certainly all lung cancers
20:42 --> 20:44when they've already spread
20:44 --> 20:46from the lungs are what we
20:46 --> 20:47call non squamous lung cancers,
20:47 --> 20:49which the majority should
20:49 --> 20:50be profiled in this way.
20:50 --> 20:53And actually it's my belief we actually
20:53 --> 20:54should probably profile all of them
20:54 --> 20:56to understand one of the
20:56 --> 20:58determinants that are causing that
20:58 --> 21:00cancer to grow because that will allow
21:00 --> 21:02us to match with the best therapy.
21:02 --> 21:04Now I'm concerned you know one
21:04 --> 21:06of the big issues we have is
21:06 --> 21:08access to care and making sure all
21:08 --> 21:10patients get this screening done.
21:10 --> 21:14One thing we're doing a lot
21:14 --> 21:16of work on is to try to get navigators
21:16 --> 21:19out to all the different areas of the city
21:19 --> 21:20to build trust.
21:22 --> 21:24Within Connecticut we want every patient
21:24 --> 21:26to have access to coming to a center
21:26 --> 21:28where they can have their tumor profiled.
21:28 --> 21:29But yes,
21:29 --> 21:31if you profile the tumor,
21:31 --> 21:33there's probably as much as a
21:33 --> 21:3420% chance you'll find something
21:34 --> 21:36that will allow you to match
21:36 --> 21:38that patient with an oral drug,
21:38 --> 21:40which in my opinion is certainly preferable
21:40 --> 21:42to giving a nonspecific chemotherapy,
21:42 --> 21:44so that's a huge advance.
21:44 --> 21:46And we're continuing to find more of
21:46 --> 21:49these and new combinations that can be used.
21:49 --> 21:49So yes,
21:49 --> 21:51that's what we call precision guided
21:51 --> 21:53therapy and for the patients who
21:53 --> 21:56don't have one of these mutations,
21:56 --> 21:58do they get standard chemotherapy
21:58 --> 22:01and have there been any advances
22:01 --> 22:03in terms of standard chemotherapy
22:03 --> 22:05for those people who either don't
22:05 --> 22:08have a druggable target or who have
22:08 --> 22:10a druggable target, and who recur?
22:10 --> 22:12Well, incredibly, the
22:12 --> 22:13answer is yes.
22:13 --> 22:15So I mentioned immunotherapy already.
22:15 --> 22:17So if someone does not
22:17 --> 22:19have one of those targets,
22:19 --> 22:21we actually can look for another target,
22:21 --> 22:23something called PDL1,
22:23 --> 22:26now PDL1 actually was in part
22:26 --> 22:27discovered by Lieping Chen, NOTE Confidence: 0.80644786
22:27 --> 22:29a professor here at Yale,
22:29 --> 22:32and he's one of our collaborators,
22:32 --> 22:33but we actually can measure
22:33 --> 22:35PDL one and tumors.
22:35 --> 22:37And if the level is very high,
22:37 --> 22:39that tells us that the
22:39 --> 22:40immunotherapy might work alone.
22:40 --> 22:42So we give those patients immunotherapy,
22:42 --> 22:43assuming they don't have
22:43 --> 22:45some reason we can't.
22:45 --> 22:47Sometimes you can't reactivate the
22:47 --> 22:48immune system because someone might
22:48 --> 22:50already have some bad arthritis or
22:50 --> 22:52know what we call an autoimmune
22:52 --> 22:54disease that precludes that.
22:54 --> 22:56But for the rest of these, again,
22:56 --> 22:58unless they have a contraindication,
22:58 --> 22:59we're giving immunotherapy in
22:59 --> 23:00combination with chemotherapy.
23:00 --> 23:02Would have been what I would have
23:02 --> 23:05guessed would have been such an active
23:05 --> 23:06therapy, but for whatever reason,
23:06 --> 23:07when you give chemotherapy
23:07 --> 23:08and immunotherapy together,
23:08 --> 23:11you at least have an additive effect,
23:11 --> 23:12meaning the chemotherapy kills
23:12 --> 23:14some of the tumor cells,
23:14 --> 23:15releases some of the proteins
23:15 --> 23:17that activate the immune system,
23:17 --> 23:19and then use these drugs that
23:19 --> 23:21we call a checkpoint
23:21 --> 23:22inhibitor that unleash the power
23:22 --> 23:24of the immune system and that's
23:24 --> 23:26become a standard of therapy.
23:26 --> 23:28Now I'll tell you that
23:28 --> 23:29those results are really
23:29 --> 23:31good and much better than
23:31 --> 23:33what we've had in the past.
23:33 --> 23:35But in my opinion we still
23:35 --> 23:36have to raise the bar,
23:36 --> 23:39so that's where clinical trials come in,
23:39 --> 23:41and it would be my my big hope that
23:41 --> 23:43in that room when a patient and a
23:43 --> 23:45physician or nurse practitioner or
23:45 --> 23:47whoever is there are meeting. someone
23:47 --> 23:49brings up, is there a clinical trial?
23:49 --> 23:51Is there something new that's
23:51 --> 23:53looking at a new agent?
23:53 --> 23:53A new drug,
23:53 --> 23:56something that might even be more active?
23:56 --> 23:57And of course,
23:57 --> 23:57that's investigation,
23:57 --> 23:59but that's really how we
23:59 --> 24:02continue to do better and better,
24:02 --> 24:06and we're inching up the
24:06 --> 24:08benefits from therapy in lung cancer.
24:11 --> 24:12So certainly clinical trials.
24:12 --> 24:15I mean, we've talked on this show a
24:15 --> 24:17lot about clinical trials and the
24:17 --> 24:19fact that people who participate
24:19 --> 24:22in clinical trials tend to do
24:22 --> 24:24better than people who don't.
24:24 --> 24:26Are all of the clinical trials in
24:26 --> 24:29lung cancer now really geared around
24:29 --> 24:32targeted therapies and immunooncology
24:32 --> 24:35or are there any clinical trials that
24:35 --> 24:37are looking at advances in standard
24:37 --> 24:40chemotherapy for people who may not
24:40 --> 24:43be eligible for those other therapies?
24:43 --> 24:46Either because they don't have a
24:46 --> 24:48target or because they don't have
24:48 --> 24:51a tumor that's expressing PDL 1.
24:52 --> 24:53Well, standard chemotherapy
24:53 --> 24:54clearly has its place,
24:54 --> 24:56and certainly in earlier stages of
24:56 --> 24:58disease before the tumors have spread
24:58 --> 25:00from the lung we're using chemotherapy
25:00 --> 25:02with radiation therapy, for example,
25:02 --> 25:05and that can be curative therapy.
25:05 --> 25:07We often add immunotherapy in afterwards,
25:07 --> 25:09but I actually personally think
25:09 --> 25:12we've pretty much come as far
25:12 --> 25:13as we can with chemotherapy.
25:13 --> 25:14It's somewhat nonspecific.
25:14 --> 25:17It can have a number of side effects.
25:17 --> 25:19However, we're finding new
25:19 --> 25:20targets like right now,
25:20 --> 25:23just in the last several months,
25:23 --> 25:25there's been data on a new target
25:25 --> 25:27against something called Kras.
25:27 --> 25:30Now Kras, which is an oncogene,
25:30 --> 25:32actually first came from a rat model.
25:33 --> 25:35Kras actually is about
25:35 --> 25:3712 to 20% of lung tumors.
25:37 --> 25:40The actual variant of this that
25:40 --> 25:42now has multiple drugs that are
25:42 --> 25:44out there is what we call G12C.
25:44 --> 25:46Probably doesn't mean much to a
25:46 --> 25:49lot of those who are listening,
25:49 --> 25:51but it's a specific abnormality that
25:51 --> 25:54occurs in 12% of lung cancer patients.
25:54 --> 25:55That's a lot of patients.
25:55 --> 25:56Remember,
25:56 --> 25:58I told you it's 1.6, 1.7
25:58 --> 26:00worldwide and there are actually agents now,
26:00 --> 26:01not approved yet,
26:01 --> 26:02but that are in clinical trials
26:02 --> 26:03showing positive results that
26:03 --> 26:05can make those tumors shrink.
26:05 --> 26:07So before I pull off some chemotherapy,
26:07 --> 26:09which by the way we will do and
26:09 --> 26:11we do need to use and sometimes we
26:11 --> 26:14even use it as we're waiting for a
26:14 --> 26:15clinical trial to become available.
26:15 --> 26:17We are beginning to study and
26:17 --> 26:19use these Kras drugs,
26:19 --> 26:20and I think that's going
26:20 --> 26:22to be the next paradigm.
26:22 --> 26:23So we've gone from chemotherapy
26:23 --> 26:24to targeted therapy,
26:24 --> 26:26to immunotherapy, and now Kras
26:26 --> 26:27which is another target.
26:27 --> 26:29But it's a broad target
26:29 --> 26:30and it always was
26:30 --> 26:31the Holy Grail,
26:31 --> 26:33there's been so many
26:33 --> 26:35approaches and ways to try to target it.
26:35 --> 26:37It's a very difficult target for
26:37 --> 26:40a cancer because I don't want
26:40 --> 26:42to get into too much detail here,
26:42 --> 26:44but just to say that the pocket that
26:44 --> 26:47we have to block with a drug is so
26:47 --> 26:49narrow that it's very hard to get a
26:49 --> 26:51drug in there to block that.
26:51 --> 26:53But scientists and chemists have
26:53 --> 26:54figured that out. Another example of
26:54 --> 26:55science drives innovation,
26:55 --> 26:58science brings new agents to the clinic.
26:58 --> 27:00Then we test them in the clinic
27:00 --> 27:02and we test them using samples
27:02 --> 27:05from patients and a series of
27:05 --> 27:07very careful studies to bring new
27:07 --> 27:09new things to standard of care.
27:09 --> 27:11So amazing progress but
27:11 --> 27:12more that needs to
27:12 --> 27:15happen. And this brings me
27:15 --> 27:17to the whole area of clinical trials.
27:17 --> 27:20For many patients historically
27:20 --> 27:22they always thought that clinical trials
27:22 --> 27:25were what you tried when there was nothing
27:25 --> 27:27else left when you had exhausted all
27:27 --> 27:30other options when the cancer was metastatic NOTE Confidence: 0.856393
27:30 --> 27:33and had spread all over the body,
27:33 --> 27:35but you're really talking about
27:35 --> 27:37clinical trials as being
27:40 --> 27:42state of the art medicine and
27:42 --> 27:44that might actually be helpful,
27:44 --> 27:46particularly in patients who are so
27:46 --> 27:49fortunate as to have detected their
27:49 --> 27:52cancer early when it's not metastatic.
27:52 --> 27:55Can you talk a little bit more about that?
27:58 --> 28:02Clinical trials really are
28:02 --> 28:05the best way and in many cases
28:05 --> 28:08to you know, treating cancer,
28:08 --> 28:10especially when you're dealing with
28:10 --> 28:13a situation where you know it is
28:13 --> 28:15incurable and you're not able to
28:15 --> 28:18treat with the standard of care,
28:18 --> 28:20I still remember the example of the
28:20 --> 28:23patient, has to be about 8 years ago,
28:23 --> 28:25we were studying a drug in clinical trial,
28:25 --> 28:27one of these immune checkpoint inhibitors
28:27 --> 28:30and he came in with advanced lung cancer.
28:30 --> 28:32He had already been to see several
28:32 --> 28:34other practitioners around
28:34 --> 28:36the state and we had one slot left
28:36 --> 28:39in this trial and you know we went
28:39 --> 28:41back and forth and he decided to
28:41 --> 28:43go on this study and he went on
28:43 --> 28:46this drug that is now approved and
28:46 --> 28:47did very well.
28:47 --> 28:48Eight years later,
28:48 --> 28:49I still get emails from him.
28:49 --> 28:50He's a photographer.
28:50 --> 28:53He sends me pictures from the wild.
28:53 --> 28:55This is where a clinical trial
28:55 --> 28:56can really pay off now,
28:56 --> 28:58because now many years before
28:58 --> 28:59approval of a drug,
28:59 --> 29:01someone took a chance on this trial
29:01 --> 29:02that the alternative would have
29:02 --> 29:04been standard of care therapy.
29:04 --> 29:05So we're not keeping anything
29:05 --> 29:06from this patient,
29:06 --> 29:08but bring that trial to bear
29:08 --> 29:10on that patient really helped him
29:10 --> 29:12and helped him live a quality life.
29:12 --> 29:14So that's what we hope for.
29:14 --> 29:16That's why clinical trials are so important.
29:16 --> 29:19And now I think, as you're alluding to,
29:19 --> 29:20we're using these clinical trials
29:20 --> 29:22in the earliest stages of disease,
29:22 --> 29:23so I know you're a surgeon,
29:23 --> 29:26so you cut out tumors,
29:26 --> 29:28but still there's a chance it will recur
29:28 --> 29:30even if you've gotten everything out.
29:30 --> 29:33So now what we're doing is we're taking
29:33 --> 29:35these best therapies in lung cancer,
29:35 --> 29:37the immunotherapy that targeted therapy
29:37 --> 29:39when using them after surgery even
29:39 --> 29:41when we see that there's no disease.
29:41 --> 29:43Knowing that these are high risk
29:43 --> 29:44of recurrence and those data,
29:44 --> 29:47some of them are already showing
29:47 --> 29:49positive results so
29:49 --> 29:50the field of research and clinical
29:50 --> 29:53care are one and the bottom line
29:53 --> 29:54is we want to give the best
29:54 --> 29:56care for patients at the best
29:56 --> 29:58possible time.
29:58 --> 30:00Dr. Roy Herbst is Ensign Professor of Medicine in Medical Oncology
30:00 --> 30:02and professor of Pharmacology
30:02 --> 30:04at the Yale School of Medicine.
30:04 --> 30:06If you have questions,
30:06 --> 30:07the address is canceranswers@yale.edu
30:07 --> 30:10and past editions of the program
30:10 --> 30:11are available in audio and written
30:12 --> 30:13form at yalecancercenter.org.
30:13 --> 30:16We hope you'll join us next week to
30:16 --> 30:18learn more about the fight against
30:18 --> 30:21cancer here on Connecticut Public Radio.

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March 28, 2021

Yale Cancer Center

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