Gastroesophageal Cancers

Transcript

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00:15 --> 00:18Welcome to Yale Cancer Answers with
00:18 --> 00:20your host doctor Anees Chagpar.
00:20 --> 00:22Yale Cancer Answers features the
00:22 --> 00:24latest information on cancer care by
00:24 --> 00:26welcoming oncologists and specialists
00:26 --> 00:28who are on the forefront of the
00:28 --> 00:30battle to fight cancer. This week
00:30 --> 00:32it's a conversation about gastroesophageal
00:32 --> 00:34cancer with Doctor Jill Lacy.
00:34 --> 00:37Doctor Lacy is a professor of medicine
00:37 --> 00:39and medical oncology at the Yale School
00:39 --> 00:42of Medicine where Doctor Chagpar is
00:42 --> 00:44a professor of surgical oncology.
00:44 --> 00:48Jill, we don't often talk
00:48 --> 00:50about gastroesophageal cancers much.
00:50 --> 00:53Tell us a little bit more about them.
00:53 --> 00:55How common are they?
00:55 --> 00:57Who do they affect?
00:57 --> 00:59What do they encompass?
00:59 --> 01:02It is somewhat of a heterogeneous group of cancers
01:02 --> 01:05and I will elaborate on that as we go along.
01:05 --> 01:08And it is not a
01:08 --> 01:10common group of cancers
01:10 --> 01:12certainly, compared to, say,
01:12 --> 01:15breast cancer or lung cancer.
01:15 --> 01:17So if you combine esophagus and
01:17 --> 01:21gastric cancer in the United States,
01:21 --> 01:23there's about 46,000 cases a year,
01:24 --> 01:25about 27,000 deaths.
01:25 --> 01:28So it is quite a lethal cancer.
01:28 --> 01:30And by contrast,
01:30 --> 01:32lung cancer over 200,000 cases.
01:32 --> 01:33Breast cancer,
01:33 --> 01:36I believe over 270,000 cases.
01:36 --> 01:37But interestingly,
01:37 --> 01:39the death rate as I indicated,
01:39 --> 01:41still is quite high.
01:41 --> 01:44You compare this, say with breast cancer,
01:44 --> 01:47where I believe we're down to in
01:47 --> 01:50the range of 40,000 deaths per year.
01:50 --> 01:53So even though it's not a common cancer,
01:53 --> 01:55it is still a significant problem
01:55 --> 01:58in terms of its lethality.
02:00 --> 02:02What's interesting about these
02:02 --> 02:04cancers is that there's quite
02:04 --> 02:06a bit of geographic variation in incidence
02:06 --> 02:09and gastric cancer actually
02:09 --> 02:11is quite common worldwide and a
02:11 --> 02:13significant public health problem.
02:13 --> 02:16It's actually the third leading cause
02:16 --> 02:18of cancer related deaths globally.
02:18 --> 02:21Over 1,000,000 cases and over 800,000 deaths.
02:21 --> 02:24So it does remain, I think,
02:24 --> 02:27a huge issue globally and still
02:27 --> 02:29problematic in the United States.
02:30 --> 02:32And on top of that,
02:32 --> 02:34gastroesophageal cancers not only are
02:34 --> 02:37gastric cancers or cancers of the stomach,
02:37 --> 02:39but also of the esophagus.
02:39 --> 02:42But the esophagus is a long tube that
02:42 --> 02:45goes all the way from essentially your
02:45 --> 02:48mouth all the way down to your stomach.
02:48 --> 02:51So talk a little bit about
02:51 --> 02:52whether those cancers,
02:52 --> 02:54the cancers of the esophagus
02:54 --> 02:56and the cancers of the stomach
02:56 --> 02:58are similar or different,
02:58 --> 03:00and whether there are different
03:00 --> 03:02types of cancers even within that.
03:02 --> 03:06Sure, so we often divide these
03:06 --> 03:09cancers into two anatomic groups.
03:09 --> 03:12Esophagus cancer, as you alluded to,
03:12 --> 03:16and gastric, or what we call stomach cancer.
03:16 --> 03:20And esophageal cancer we now know really
03:20 --> 03:23is comprised of two very distinct types,
03:23 --> 03:24really essentially different diseases.
03:26 --> 03:29One type is called squamous cell cancer
03:29 --> 03:32an under the microscope and in terms of
03:32 --> 03:35its molecular biology and risk factors,
03:35 --> 03:38it's actually quite similar to cancers of
03:38 --> 03:42the throat and the head and neck region.
03:42 --> 03:44The risk factor there is tobacco
03:44 --> 03:46and alcohol in poverty.
03:46 --> 03:47And Interestingly,
03:47 --> 03:49the incidence of squamous cell
03:49 --> 03:51carcinoma of the esophagus has
03:51 --> 03:53really dropped dramatically,
03:53 --> 03:55particularly in the Western world,
03:55 --> 03:57so that's the good news.
03:57 --> 03:59The other type of esophagus
03:59 --> 04:01cancer is called adenocarcinoma,
04:01 --> 04:03and then actually arises at the
04:03 --> 04:06bottom of the esophagus where it
04:06 --> 04:08connects in with the stomach,
04:08 --> 04:10often referred to as
04:10 --> 04:11gastroesophageal junction cancer,
04:11 --> 04:14and that looks much more like a typical
04:14 --> 04:17gastric cancer under the microscope.
04:17 --> 04:19And actually is much more similar to
04:19 --> 04:22gastric cancer than it is to squamous
04:22 --> 04:24cell cancers of the esophagus.
04:24 --> 04:25And they are.
04:25 --> 04:27They have different risk factors,
04:27 --> 04:28so I,
04:28 --> 04:30for I alluded to the risk factors for
04:30 --> 04:34squamous cell of these saw fickas it's
04:34 --> 04:35predominantly tobacco and alcohol
04:35 --> 04:38as we see with head and neck cancer.
04:38 --> 04:41For the adenocarcinomas of the esophagus
04:41 --> 04:45that arise at the bottom of the esophagus.
04:45 --> 04:47What's interesting about that
04:47 --> 04:51is that there actually has been
04:51 --> 04:54quite a dramatic increase in the
04:54 --> 04:56incidence of this particular entity.
04:56 --> 04:58Gastroesophageal junction adenocarcinoma,
04:58 --> 05:00particularly in Caucasian males,
05:00 --> 05:03a great male predominant we don't
05:03 --> 05:06fully understand that increase some
05:06 --> 05:09of the risk factors that are linked.
05:09 --> 05:13Two adenocarcinoma of the esophagus
05:13 --> 05:16are high BMI or obesity.
05:16 --> 05:18Possibly Dyett gastro oesophageal
05:18 --> 05:22reflux disease is certainly risk
05:22 --> 05:24factor in some cases,
05:24 --> 05:27but smoking and alcohol do not seem
05:27 --> 05:32to play a predominant role in risk
05:32 --> 05:35factor the gastroesophageal adenocarcinomas.
05:35 --> 05:39Then you get into the stomach an we're
05:39 --> 05:42talking about classic gastric cancer.
05:42 --> 05:45And there what's very interesting is
05:45 --> 05:50that there's been a progressive decline.
05:50 --> 05:53Across the globe and in the United States.
05:53 --> 05:55In the incidence of gastric cancer
05:55 --> 05:57as it was the number one cause
05:57 --> 05:59of cancer related deaths globally
05:59 --> 06:01until about the 1980s,
06:01 --> 06:03when it was surpassed by lung cancer
06:03 --> 06:06and there are a lot of interesting
06:06 --> 06:08theories about why that is.
06:08 --> 06:11And we do know that there are some risk
06:11 --> 06:14factors for stomach or gastric cancer,
06:14 --> 06:16and these include some environmental
06:16 --> 06:18and lifestyle risk factors.
06:18 --> 06:21One of the most prominent is a
06:21 --> 06:23bacteria called Helicobacter pylori,
06:23 --> 06:26which is quite prevalent and some
06:26 --> 06:29strains of that bacteria are cancer
06:29 --> 06:32causing and do increase the risk of
06:32 --> 06:35gastric cancer through been a lot of
06:35 --> 06:37studies over the decades about diet.
06:37 --> 06:39So it does seem that.
06:39 --> 06:42Salt preserved and smoked foods increase
06:42 --> 06:45the risk as well as dietze that are
06:45 --> 06:48low in fresh fruits and vegetables.
06:48 --> 06:50Modest risks risk factors would be
06:50 --> 06:52smoking and obesity and probably
06:52 --> 06:54lower social economic status.
06:54 --> 06:57So there are a lot of differences,
06:57 --> 06:59not only anatomically and in terms
06:59 --> 07:02of the pathology under the microscope
07:02 --> 07:05but also risk factors, and it's
07:05 --> 07:07interesting deals that you mentioned
07:07 --> 07:09that the oesophageal cancer rate
07:09 --> 07:11and the gastric cancer rate.
07:11 --> 07:14Both seems to have dropped,
07:14 --> 07:16but gastroesophageal cancers,
07:16 --> 07:20those cancers that occur at that junction,
07:20 --> 07:23the add node cancers.
07:23 --> 07:25Have increased Ann.
07:25 --> 07:28You mentioned that we we don't know
07:28 --> 07:31why exactly those have increased,
07:31 --> 07:34but do we have any insight into
07:34 --> 07:38what played a role in decreasing the
07:38 --> 07:41incidence of oesophageal cancers and
07:41 --> 07:42of gastric cancers?
07:42 --> 07:45So for squamous cell carcinoma
07:45 --> 07:48of the esophagus it is related
07:48 --> 07:50to a decrease in smoking.
07:50 --> 07:52And improvements in social
07:52 --> 07:54economic status and nutrition.
07:54 --> 07:58Those seem to be quite linked to squamous
07:58 --> 08:02of the esophagus and for gastric cancer,
08:02 --> 08:06we do think that it does relate
08:06 --> 08:08to decreasing incidence of
08:08 --> 08:11H. Pylori colonization or infection related,
08:11 --> 08:12likely due to refrigeration
08:12 --> 08:15over the last century or so.
08:15 --> 08:19So in areas of the world that are
08:19 --> 08:21underdeveloped we see
08:21 --> 08:24a drop in the incidence of gastric cancer,
08:24 --> 08:26so that's the prevailing theory.
08:27 --> 08:29But you know, it's interesting
08:29 --> 08:30that despite these advances,
08:30 --> 08:34and certainly there's a long way to go,
08:34 --> 08:36this is still, as you mentioned,
08:36 --> 08:38a fairly lethal cancer
08:38 --> 08:40when we think about gastroesophageal
08:40 --> 08:41cancers as a whole,
08:41 --> 08:44is that because they tend to
08:44 --> 08:46present at late stages in general?
08:47 --> 08:51I think it's a combination of factors.
08:51 --> 08:53Yes they are lethal cancers,
08:53 --> 08:56and that's why even though they're
08:56 --> 08:58not so common in the United States,
08:58 --> 09:00they're still very problematic.
09:00 --> 09:03So the five year cure rate for
09:03 --> 09:06esophaeal cancer was only about 20%.
09:06 --> 09:09It's a little bit higher for gastric cancer,
09:09 --> 09:12about 30%, and I think the reasons for
09:12 --> 09:15this are multi factorial if you will.
09:15 --> 09:19In some cases, due to a delay in diagnosis,
09:19 --> 09:23but I don't think that's the major reason.
09:23 --> 09:26I think it has much to do with the
09:26 --> 09:29inherent biology of these tumors.
09:29 --> 09:31A propensity to disseminate
09:31 --> 09:32or spread early on,
09:32 --> 09:35and then the need for better
09:35 --> 09:37and more effective therapies to
09:37 --> 09:39deal with disseminated disease.
09:39 --> 09:42I would add that in contrast to
09:42 --> 09:45the common cancers such as breast,
09:45 --> 09:46colorectal, lung, and cervical
09:46 --> 09:49there is no widespread screening
09:49 --> 09:50for these cancers,
09:50 --> 09:53at least in the Western world.
09:54 --> 09:56But it is a little bit different in Asia
09:56 --> 09:59and therefore early detection
09:59 --> 10:02is less likely to happen with
10:02 --> 10:04these cancers as opposed to
10:04 --> 10:05breast cancer,
10:05 --> 10:08so that certainly would be a contributing
10:08 --> 10:12factor.
10:12 --> 10:14Talk a little bit about the differences in screening in Asia.
10:15 --> 10:18How do people in Asia get screened for
10:18 --> 10:20esophageal cancers and why
10:20 --> 10:24hasn't that been adopted in the US?
10:24 --> 10:26Usually we find screening to be more
10:26 --> 10:29prevalent in the Western world than
10:29 --> 10:31we do in less developed countries.
10:32 --> 10:34In terms of
10:34 --> 10:37screening in Asia for gastric cancer
10:37 --> 10:39they do pretty sophisticated
10:39 --> 10:41radiographic studies to look at
10:41 --> 10:43the surface of the stomach to
10:43 --> 10:46see if there are irregularities,
10:46 --> 10:49and then for esophagus cancer
10:49 --> 10:51screening modalities is to have
10:51 --> 10:53patients swallow a balloon and sort
10:53 --> 10:56of pull it up through the esophagus
10:56 --> 10:58and you pull off abnormal cells
10:58 --> 11:01in the lining of the esophagus.
11:01 --> 11:04And those are two screening modalities.
11:04 --> 11:08That can be applied widely in the United
11:08 --> 11:11States because it is an uncommon cancer.
11:11 --> 11:15I think there's just not been a lot
11:15 --> 11:18of focus on widespread screening
11:18 --> 11:20for these cancers.
11:20 --> 11:23So you mentioned that these cancers
11:23 --> 11:25tend to, because of their biology,
11:25 --> 11:27be more advanced
11:27 --> 11:30at the time of presentation
11:30 --> 11:33and more rapidly get to a more
11:33 --> 11:35advanced or metastatic stage,
11:35 --> 11:37what proportion of
11:37 --> 11:39these patients present with
11:39 --> 11:41advanced or metastatic disease,
11:41 --> 11:43out of all
11:43 --> 11:46the gastroesophageal cancers that you see?
11:46 --> 11:50Still the majority of the
11:50 --> 11:53patients are presenting with non
11:53 --> 11:56disseminated or nonmetastatic disease,
11:56 --> 12:00so that's the good news.
12:00 --> 12:03But despite that, again
12:03 --> 12:04oftentimes particularly
12:04 --> 12:06with the more advanced but
12:06 --> 12:07still nonmetastatic cases,
12:07 --> 12:11there is what we call a cult dissemination,
12:11 --> 12:14and that is where we look to additional
12:14 --> 12:16therapies such as chemotherapy
12:16 --> 12:18to try to increase security.
12:18 --> 12:20You know, it's something that
12:20 --> 12:22we've been doing for several
12:22 --> 12:25decades in the breast cancer world,
12:25 --> 12:27and certainly has a role
12:27 --> 12:29in these cancers as well.
12:29 --> 12:30Even in those patients who
12:30 --> 12:32appear to have localized and
12:32 --> 12:34potentially curable disease.
12:34 --> 12:38And I want to kind of get
12:38 --> 12:41into how exactly we treat patients,
12:41 --> 12:43and so with those patients with
12:43 --> 12:45localized disease, can we treat
12:45 --> 12:47these patients for curative intent?
12:47 --> 12:50And how do we do that?
12:50 --> 12:53Absolutely, patients who
12:53 --> 12:55present with nonmetastatic disease,
12:55 --> 12:57so no evidence of dissemination
12:57 --> 13:00to other sites in the body,
13:00 --> 13:02and that we determined
13:02 --> 13:04simply by getting imaging,
13:04 --> 13:07usually a CAT scan or in
13:07 --> 13:10some cases a PET scan.
13:10 --> 13:13And for those patients there is a path
13:13 --> 13:17to cure for many of those patients,
13:17 --> 13:19and that often involves
13:19 --> 13:21surgery as the centerpiece
13:21 --> 13:24of the cure and then in many cases where
13:24 --> 13:28the disease is more locally advanced,
13:28 --> 13:30we will need adjunctive therapies
13:30 --> 13:32in addition to surgery to
13:32 --> 13:34further increase the cure rate.
13:34 --> 13:36And that's true both for
13:36 --> 13:38esophagus cancer and for gastric
13:38 --> 13:41cancer.
13:41 --> 13:45When the disease has spread or is more advanced,
13:45 --> 13:49I would imagine that therapies can be a
13:49 --> 13:53little bit more challenging or problematic
13:53 --> 13:55but I do understand that
13:55 --> 13:57there are some new advances that
13:57 --> 14:00may help patients who have more
14:00 --> 14:02advanced or metastatic disease.
14:02 --> 14:05So I want to get into all of that,
14:05 --> 14:08but first we need to take a short
14:08 --> 14:10break for a medical minute,
14:10 --> 14:12so please stay tuned to learn more
14:12 --> 14:14about gastroesophageal cancer
14:14 --> 14:17with my guest Doctor Jill Lacy.
14:17 --> 14:20Support or Yale Cancer Answers comes from AstraZeneca,
14:20 --> 14:22a science LED biopharmaceutical company
14:22 --> 14:23dedicated to partnering across the
14:23 --> 14:25oncology community to improve outcomes
14:25 --> 14:27across various stages of cancer.
14:27 --> 14:34More at astrazeneca-us.com. This is a
14:34 --> 14:36medical minute about breast cancer,
14:36 --> 14:38the most common cancer in
14:38 --> 14:39women. In Connecticut alone,
14:39 --> 14:41approximately 3000 women will be
14:41 --> 14:44diagnosed with breast cancer this year,
14:44 --> 14:46but thanks to earlier detection,
14:46 --> 14:47non invasive treatments,
14:47 --> 14:48and novel therapies,
14:48 --> 14:51there are more options for patients to
14:51 --> 14:54fight breast cancer then ever before.
14:54 --> 14:56Women should schedule a baseline
14:56 --> 14:58mammogram beginning at age 40 or
14:58 --> 15:00earlier if they have risk factors
15:00 --> 15:02associated with breast cancer.
15:02 --> 15:04Digital breast tomosynthesis or
15:04 --> 15:063D mammography is transforming
15:06 --> 15:07breast screening by significantly
15:07 --> 15:09reducing unnecessary procedures
15:09 --> 15:12while picking up more cancers and
15:12 --> 15:15eliminating some of the fear
15:15 --> 15:17and anxiety many women experience.
15:17 --> 15:19More information is available
15:19 --> 15:20at yalecancercenter.org.
15:20 --> 15:23You're listening to Connecticut Public Radio.
15:23 --> 15:24Welcome
15:24 --> 15:26back to Yale Cancer Answers.
15:26 --> 15:28This is doctor Anees Chagpar
15:28 --> 15:31and I'm joined tonight by
15:31 --> 15:33my guest doctor Jill Lacy.
15:33 --> 15:36We're talking about gastroesophageal
15:36 --> 15:38cancer and right before the break
15:38 --> 15:40Jill was telling us about
15:40 --> 15:43how this is a rare cancer,
15:43 --> 15:45but one that really is fatal
15:45 --> 15:47for some patients and
15:47 --> 15:49especially difficult or perhaps
15:49 --> 15:52more challenging to treat in the
15:52 --> 15:54advanced and metastatic setting.
15:54 --> 15:57So Jill tell us a little bit more
15:57 --> 16:00about historically the options that
16:00 --> 16:03we've had for advanced metastatic
16:03 --> 16:05gastroesophageal cancers and
16:05 --> 16:07some of the new developments that
16:07 --> 16:10maybe can give patients more hope.
16:11 --> 16:15For most of my career,
16:15 --> 16:17when patients develop
16:17 --> 16:19metastatic or disseminated
16:19 --> 16:21esophageal or gastric cancers,
16:21 --> 16:26we were able to offer some treatments,
16:26 --> 16:29but the prognosis was poor and the
16:29 --> 16:33survival was relatively short and those
16:33 --> 16:36treatments up until relatively recently
16:36 --> 16:40were basically the use of chemotherapy,
16:40 --> 16:42or cytotoxic drugs.
16:42 --> 16:44Traditional chemotherapy drugs.
16:44 --> 16:46And those drugs,
16:46 --> 16:48often provided some palliation
16:48 --> 16:51and mostly prolong survival,
16:51 --> 16:54but it was unusual to
16:54 --> 16:55see long-term survivors,
16:55 --> 17:00and we were not curing patients
17:00 --> 17:02with those treatments.
17:03 --> 17:06What changed more recently?
17:07 --> 17:11There have been some very exciting advances in
17:11 --> 17:14the treatment of metastatic, or disseminated,
17:14 --> 17:17both esophageal and gastric cancers.
17:17 --> 17:21The first advance came about a decade
17:21 --> 17:27ago and this was in the area of gastric
17:27 --> 17:29and gastroesophageal adenocarcinomas.
17:29 --> 17:34And what we had learned was that these are
17:34 --> 17:37heterogeneous from a molecular perspective.
17:37 --> 17:42And about 20 to 30% of these tumors carried
17:42 --> 17:46high levels of a protein called Her 2,
17:46 --> 17:48and we knew that this protein
17:48 --> 17:52also was present in breast cancer.
17:54 --> 17:57And a drug had been developed
17:57 --> 18:00called an antibody that
18:00 --> 18:03targeted her 2 in breast cancer and
18:03 --> 18:05it was extraordinarily effective.
18:05 --> 18:08That drug is trastuzumab, or Herceptin.
18:08 --> 18:09And so it was
18:09 --> 18:12theorized that perhaps
18:12 --> 18:14Herceptin would have
18:14 --> 18:16activity in the her 2 positive
18:16 --> 18:19gastric and esophageal adenocarcinomas.
18:19 --> 18:23So there was a large global effort
18:23 --> 18:25to answer that question.
18:25 --> 18:28Patients with advanced disease, metastatic
18:28 --> 18:32or stage four were assigned to get
18:32 --> 18:35the standard of care at that time,
18:35 --> 18:37chemotherapy with two drugs
18:37 --> 18:39or chemotherapy plus
18:39 --> 18:41Herceptin and the results
18:41 --> 18:44of that study were really quite stunning
18:44 --> 18:47in that survival was significantly
18:47 --> 18:49improved for those patients who
18:49 --> 18:52received Herceptin.
18:52 --> 18:55So I would say that was the first
18:55 --> 18:58big advance and changed the paradigm
18:58 --> 19:01about how we think about these
19:01 --> 19:05cancers in terms of looking at the
19:05 --> 19:07molecular profile and thinking
19:07 --> 19:09about using targeted therapies.
19:09 --> 19:12So that was very exciting.
19:12 --> 19:14And then what happened?
19:14 --> 19:16It sounds like there's
19:16 --> 19:18another shoe that's about to drop.
19:18 --> 19:22There is, so in the breast cancer world
19:22 --> 19:24what followed on after the discovery
19:24 --> 19:26of Herceptin was the development of
19:26 --> 19:29other drugs that targeted this protein
19:29 --> 19:31Her 2 and there were additional
19:31 --> 19:34drugs that were developed and
19:34 --> 19:36approved and that were effective.
19:36 --> 19:38But unfortunately when those drugs
19:38 --> 19:40were tested in gastroesophageal
19:40 --> 19:43cancers that were positive for her 2,
19:43 --> 19:46They were not effective and that was
19:46 --> 19:49disappointing and so we were learning
19:49 --> 19:52that her 2 positive gastroesophageal
19:52 --> 19:55cancer is not the same thing as
19:55 --> 19:57her 2 positive breast cancer.
19:57 --> 20:00That's interesting. So wait a second,
20:00 --> 20:02what you're saying is that
20:02 --> 20:05trust Herceptin worked in her
20:05 --> 20:072 positive gastric cancer,
20:07 --> 20:09but Pertuzumab, I'm assuming
20:09 --> 20:12that you meant pertuzumab,
20:12 --> 20:15which also targets her 2, did not work.
20:18 --> 20:21It did not in the studies that were conducted as well as the antibody
20:21 --> 20:24drug conjugate TDM one and lapatinib.
20:26 --> 20:27Any why was that?
20:27 --> 20:30I mean do they think that
20:30 --> 20:32there was something particular about
20:32 --> 20:36her 2 or was it or about Herceptin
20:36 --> 20:39versus the other drugs in terms
20:39 --> 20:42of what particular subunit of her 2
20:42 --> 20:43that we're targeting?
20:43 --> 20:45Or what was the
20:45 --> 20:47hypothesis behind why
20:47 --> 20:50one drug would work, but the
20:50 --> 20:51others didn't?
20:51 --> 20:54That is a great question and I don't
20:55 --> 20:57know that we have all the answers.
20:57 --> 21:00We do know that gastroesophageal cancers
21:00 --> 21:02are much more heterogeneous in terms
21:02 --> 21:04of their levels of expression are
21:04 --> 21:06more likely to lose expression overtime,
21:06 --> 21:08so that's one issue.
21:08 --> 21:11Some of it may have been related to how
21:11 --> 21:13the studies were designed and conducted,
21:13 --> 21:16but I don't think we fully understand
21:16 --> 21:19why we don't see the exact same activity
21:19 --> 21:22of some of these agents in gastric
21:22 --> 21:24and esophageal adenocarcinomas that we're
21:24 --> 21:26seeing in breast cancer.
21:26 --> 21:29Sorry to interrupt, but it still
21:29 --> 21:32sounds like there was another shoe that
21:32 --> 21:33was going to drop.
21:33 --> 21:36Well, I think we're very excited in
21:36 --> 21:39that it does appear that there is
21:39 --> 21:42going to be newer generations of her
21:42 --> 21:452 targeting agents that are going
21:45 --> 21:47to be effective in gastric cancer.
21:47 --> 21:50So one of them is a very
21:50 --> 21:52interesting drug that is
21:52 --> 21:55also used in breast cancer now very recently
21:55 --> 21:58where you take Herceptin and you
21:59 --> 22:01link it up biochemically to a
22:01 --> 22:02chemotherapeutic drug.
22:09 --> 22:13And that has been approved in breast cancer.
22:13 --> 22:15That's her 2 positive and has been
22:15 --> 22:18tested now and her 2 positive gastroesophageal
22:18 --> 22:20adenocarcinomas in patients
22:20 --> 22:23who have already been on trastuzumab
22:23 --> 22:25and have failed treatment and the
22:25 --> 22:27results really were stunning.
22:27 --> 22:29With major shrinkage in more
22:29 --> 22:30than half of the patients,
22:30 --> 22:32which is not something that we
22:32 --> 22:34typically see in this disease.
22:34 --> 22:37Really with any line of therapy
22:37 --> 22:38and very impressive survival.
22:38 --> 22:40So this is very exciting.
22:40 --> 22:42There was a New England Journal
22:42 --> 22:44of Medicine paper regarding this
22:44 --> 22:45data earlier this year,
22:45 --> 22:47and I do believe this
22:47 --> 22:49new drug will be approved not
22:49 --> 22:52only in breast cancer but also in her
22:52 --> 22:542 positive gastroesophageal cancer.
22:54 --> 22:57So we're very excited about that.
22:57 --> 22:58And again,
22:58 --> 23:01this is for our patients who
23:01 --> 23:05have her two positive tumors.
23:05 --> 23:08So it's not for all comers.
23:08 --> 23:09So that's one development.
23:09 --> 23:13And then I think we will also see
23:13 --> 23:15some newer generation antibodies
23:15 --> 23:18that are similar to trastuzumab but
23:18 --> 23:21more potent in recruiting the immune
23:21 --> 23:25system into action to kill the cancer.
23:25 --> 23:29And so one of those is called margetuximab,
23:29 --> 23:32so quite similar to trastuzumab,
23:32 --> 23:34but it enhances the immune response
23:34 --> 23:37and we've already seen really positive
23:37 --> 23:40and exciting preliminary data when
23:40 --> 23:43it is combined with immunotherapy.
23:43 --> 23:46And there's a very exciting on
23:46 --> 23:48going clinical trial
23:48 --> 23:50looking at this combination of
23:50 --> 23:53margetuximab in immunotherapy with
23:53 --> 23:55chemotherapy in newly diagnosed patients.
23:55 --> 23:57So we're very excited
23:57 --> 24:00about the second and third generation
24:00 --> 24:02iterations
24:02 --> 24:05and then there are other novel antibodies
24:05 --> 24:08targeting her 2 that are being developed,
24:08 --> 24:11so I do think that the field is
24:11 --> 24:13really going to open up in terms of
24:13 --> 24:16treatment of her 2 positive stage
24:16 --> 24:19for gastroesophageal adenocarcinoma.
24:19 --> 24:21I'm very hopeful that the prognosis
24:21 --> 24:24for these patients will improve
24:24 --> 24:25significantly with these therapies.
24:26 --> 24:28But there's still a large fraction of
24:28 --> 24:31patients who are her 2 negative,
24:32 --> 24:34So what about them?
24:34 --> 24:35Does standard immunotherapy,
24:35 --> 24:38for example with checkpoint inhibitors,
24:38 --> 24:41help them?
24:41 --> 24:44This is where there's some excitement really
24:44 --> 24:47just in the past few months.
24:47 --> 24:49So we hear a lot about
24:49 --> 24:51immune checkpoint inhibitors.
24:51 --> 24:54Drugs like KEYTRUDA
24:54 --> 24:57or Opdivo in colon cancer,
24:57 --> 24:58lung cancer, Melanoma,
24:58 --> 25:01and many other cancers where
25:01 --> 25:02these immunotherapeutic agents
25:02 --> 25:04have really been game changers.
25:04 --> 25:08These agents in the way the studies
25:08 --> 25:11have been done to date have not
25:11 --> 25:14appeared to have a significant
25:14 --> 25:17impact in gastroesophageal cancer.
25:17 --> 25:20But there is some activity and we're
25:20 --> 25:23learning more about who should
25:23 --> 25:26get these agents who will benefit
25:26 --> 25:29most when and how to use them.
25:29 --> 25:32And I think that's where the field is
25:32 --> 25:35moving forward in a very positive way.
25:35 --> 25:38So there are already FDA approvals
25:41 --> 25:43for classical immune checkpoint inhibitors,
25:43 --> 25:44and gastroesophageal cancer,
25:44 --> 25:47so we can use KEYTRUDA
25:47 --> 25:49in patients who failed standard
25:49 --> 25:52several lines of standard therapy
25:52 --> 25:56if their tumor expresses the target PDL1
25:56 --> 25:59that's for gastric and gastroesophageal
25:59 --> 26:01adenocarcinomas and it
26:01 --> 26:04is also approved in esophageal
26:04 --> 26:06squamous cell carcinoma after
26:06 --> 26:08standard initial chemotherapy works.
26:08 --> 26:11And the results are very
26:11 --> 26:14impressive there and it's also active
26:14 --> 26:17in a very small subset of patients
26:17 --> 26:21whose tumors are characterized by what
26:21 --> 26:23we call microsatellite instability.
26:23 --> 26:26Or loss of a DNA repair mechanism.
26:26 --> 26:29These tumors are characterized by lots
26:29 --> 26:31of mutations in abnormal proteins.
26:31 --> 26:34And respond very well to
26:34 --> 26:35checkpoint inhibitors,
26:35 --> 26:38but that's a small percentage in the
26:38 --> 26:41range of three to 5%.
26:41 --> 26:44So what's most exciting is data that
26:44 --> 26:48we heard really just a few months ago
26:48 --> 26:50regarding the incorporation of
26:50 --> 26:52immune checkpoint inhibitors into
26:52 --> 26:55the initial treatment of stage four,
26:55 --> 26:57gastric and esophageal cancers.
26:58 --> 27:01And so there were a couple of
27:01 --> 27:04studies that were presented at
27:04 --> 27:07the major meeting in Europe.
27:07 --> 27:08Both had similar designs.
27:08 --> 27:11One was focused on gastroesophageal
27:11 --> 27:14adenocarcinoma and in this study
27:14 --> 27:16patients were given either the
27:16 --> 27:18standard two drug chemotherapy,
27:18 --> 27:21standard of care, or those same
27:21 --> 27:23two chemotherapy drugs with no
27:23 --> 27:25OPDIVO and again
27:25 --> 27:28really exciting results with the
27:28 --> 27:30significant improvement in survival.
27:30 --> 27:33A higher response rate and
27:33 --> 27:34excellent tolerability.
27:34 --> 27:37So lots of excitement about that.
27:37 --> 27:41And then a second study with a very
27:41 --> 27:44similar design of chemo or chemo,
27:44 --> 27:47with in this case KEYTRUDA
27:47 --> 27:52and here the focus was an again on esophageal cancer,
27:52 --> 27:54both squamous and adenocarcinoma,
27:54 --> 27:57and again a similar exciting result showing
27:57 --> 28:00a significant improvement in survival.
28:00 --> 28:03Actually a doubling of survival at two years.
28:03 --> 28:07So this is really great news
28:08 --> 28:10for patients with these diseases,
28:10 --> 28:13and I do think that these studies
28:13 --> 28:16will ultimately lead to new
28:16 --> 28:18indications and FDA approvals.
28:18 --> 28:20We're not there yet,
28:20 --> 28:22but I think we're
28:22 --> 28:24getting close.
28:24 --> 28:27What about in terms of other targeted therapies?
28:27 --> 28:29You know we have talked on this
28:29 --> 28:32show with other people from other
28:32 --> 28:35disease groups and other cancer
28:35 --> 28:37types about looking at cancers
28:38 --> 28:40and seeing what genes are turned on
28:40 --> 28:44and turned off to try to target these?
28:44 --> 28:46How much of that goes on in
28:46 --> 28:47gastroesophageal cancers?
28:47 --> 28:50Are we getting there in terms of
28:50 --> 28:52genomic analysis of these cancers
28:52 --> 28:55and being able to target them
28:55 --> 28:56aside from her 2?
28:57 --> 29:00Yes, absolutely, so we routinely
29:00 --> 29:03recommend that all patients with advanced
29:03 --> 29:05gastroesophageal adenocarcinomas
29:05 --> 29:08and squamous cell carcinomas
29:08 --> 29:12undergo what is referred to as tumor
29:12 --> 29:15profiling or molecular profiling to look
29:15 --> 29:19at the genetic makeup of the tumor
29:19 --> 29:23to see what makes it tick.
29:23 --> 29:26Now we haven't identified a high
29:26 --> 29:29frequency of recurring targets.
29:29 --> 29:31To date, other than her 2,
29:31 --> 29:34but there are targets that are
29:34 --> 29:36expressed with reasonable frequency
29:36 --> 29:39that are what we call actionable or
29:39 --> 29:41druggable where we can develop a
29:41 --> 29:44drug or have a drug that potentially
29:44 --> 29:46could target that abnormality.
29:46 --> 29:48So we've talked at length today
29:48 --> 29:50already about her 2,
29:50 --> 29:52and that's a critically important
29:52 --> 29:55target in those 25 to 30% patients
29:55 --> 29:57and again another exciting development
30:00 --> 30:03that I think we are on the cusp of is another targeted therapy.
30:03 --> 30:05This again is an antibody
30:08 --> 30:10that is targeting another
30:10 --> 30:12protein called fibroblast growth
30:12 --> 30:15factor receptor and
30:15 --> 30:17like her 2,
30:17 --> 30:20is expressed on the surface and
30:20 --> 30:24again in about probably 20 to 30% of
30:24 --> 30:27patients is expressed at very high
30:27 --> 30:31levels or overexpressed and this has been
30:31 --> 30:34a target for the development of an antibody,
30:35 --> 30:37and we heard really just this
30:37 --> 30:40week from a press release,
30:40 --> 30:42so we haven't seen the data,
30:42 --> 30:45so we have to stay tuned, that a
30:45 --> 30:48study looking at patients who have
30:48 --> 30:51this target looking at
30:51 --> 30:54these patients and combining the
30:54 --> 30:57antibody that targets FG FR2 with
30:57 --> 30:59chemotherapy and comparing that to
30:59 --> 31:02standard of care chemotherapy alone.
31:02 --> 31:05And at least based on the press release,
31:05 --> 31:08this looks like it will be a positive study.
31:08 --> 31:09So again,
31:09 --> 31:11quite a bit of excitement and
31:11 --> 31:13buzz in the field.
31:21 --> 31:23So there's one example,
31:23 --> 31:25there are several others and drugs in
31:25 --> 31:28the pipeline looking at other targets.
31:28 --> 31:28Doctor Jill Lacy
31:28 --> 31:30is a professor of
31:30 --> 31:32medicine and medical oncology
31:32 --> 31:34at the Yale School of Medicine.
31:34 --> 31:36If you have questions,
31:36 --> 31:37the address is canceranswers@yale.edu
31:37 --> 31:40and past editions of the program
31:40 --> 31:42are available in audio and written
31:42 --> 31:43form at yalecancercenter.org.
31:43 --> 31:46We hope you'll join us next week to
31:46 --> 31:48learn more about the fight against
31:48 --> 31:51cancer here on Connecticut Public Radio.

Information

Gastroesophageal Cancers with guest Dr. Jill Lacy November 29, 2020 Yale Cancer Center visit: http://www.yalecancercenter.org email: canceranswers@yale.edu call: 203-785-4095