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Jan 21, 2021

In today's episode, Dr. Marcia Cruz-Correa, executive director of the University of Puerto Rico Comprehensive Cancer Center, discusses key abstracts from the 2021 Gastrointestinal Cancers Symposium.



ASCO Daily News: Welcome to the ASCO Daily News podcast. I'm Geraldine Carroll, a reporter for the ASCO Daily News. My guest today is Dr. Marcia Cruz-Correa. She is the executive director of the University of Puerto Rico Cancer Center, where she also leads the gastrointestinal cancer program.

Dr. Cruz-Correa served as the chair of the 2021 Gastrointestinal Cancer Symposium, and joins me today to share some highlights from the meeting. She receives research funding from the Pan American Center for Oncology Trials. Dr. Cruz-Correa, welcome to the ASCO Daily News podcast.

Dr. Marcia Cruz-Correa: Thank you very much. My pleasure to be part of this podcast.

ASCO Daily News: The symposium covered a vast array of studies across the spectrum of gastrointestinal malignancies, and it explored some very timely and important issues, including disparities in cancer care and COVID-19 vaccines. What are some of the highlights that you'd like to share with us today?

Dr. Marcia Cruz-Correa: Many people contributed to making GI21 an overwhelming success. This was a challenge amid all the distance and all the logistics. But we really were able to engage a community of practicing medical oncologists, surgical oncologists, gastroenterologists among many other health care providers and also allied professions, as well as industry. And I can tell you that there were a few overarching themes that I want to maybe highlight.

And for me, one of them was how global we are as a community of practicing physicians and oncologists. We deal with patients that present usually with advanced disease. And we try to integrate the best science, and marry that with what you have available.

And one aspect that was very important, and was seen in multiple abstracts, is that nowadays, even though we have targeted therapy and we try to identify that special biomarker that is present in the patients that you're treating, unfortunately, sometimes one marker is not enough. And several abstracts highlighted the importance of combination therapy, where you have chemotherapy therapy, classic cytotoxic therapy, along with targeted therapy. And there were a few abstracts that look into that.

There's one which is the IMbrave study, and the CheckMate 040 study. Those are Abstract 478, where the investigators were highlighting how combining therapy for patients with hepatocellular carcinoma--it's really the way to go, and they look at three different immunotherapy dosing, with two checkpoint inhibitors, and then a chemotherapy, specifically cabozantinib. And they were able to show that the combination of agents seemed to work better.

And this was repeated in several abstracts, showing you that it's not a one drug fits all. And I think that that's important to keep in mind. Because I think as a scientist, we like to simplify, right? We like to go down to one target, one disease, one treatment. And that's the best way to think about processes, right? Because it's cleaner.

But human beings are not that simple, right? We have the heterogeneity, not only in the genes that we inherit, but also in the cells that become damaged, and then they are malignant cells. So when you think about one target, of course, that's the simplest way to see it, and it's wonderful that we can actually evaluate that. But that will not be the answer for all the patients.

So we're learning that even when you classify it and you identify a signature for that particular patient, it might be that it only represents a small percentage of all the signatures that the patient has. So it's almost like in one way, we are trying to simplify, but in the other one, we realize the complexity of dealing with patients with cancer.

ASCO Daily News: Absolutely. Are there other abstracts that stand out for you that you believe will be practice-changing?

Dr. Marcia Cruz-Correa: Yes. Yes, absolutely. There are a few. I want to mention one abstract, Abstract 160. It's the FIGHT trial, which stands for first-line treatment of advanced gastric/gastroesophageal junction adenoma. I love the title, FIGHT. Because that's what we do with our patients, right?

But this abstract was wonderful, because it demonstrated that evaluating a specific agent--in fact, in this particular trial, we were looking at the combination therapy for patients with gastric cancer. And the biomarker that was evaluated, it's FGFR2b. Basically, it's in the epithelium. It's a receptor that was evaluated by doing immunohistochemistry.

And this is quite exciting, because remember, most of the technology that we use nowadays, it's very advanced, so we use next-generation sequencing, and we look at copy numbers and so forth and so on. But immunohistochemistry is when we use antibodies to look for the presence or absence of a protein. And this is widely available, and the investigators were able to show that when a patient tumor had over-expression of this particular protein, FGFR2b--first of all, it was present about a third of all patients with gastric cancer. When the patient had that, the addition of an antibody--a targeted therapy, which is called bemarituzumab--to the standard therapy was better. And so again, seeing the concept of combining classic cytotoxic agents with targeted therapy.

And unfortunately, when we think about gastric cancer and gastroesophageal cancer, we see that disproportionately more diverse populations are affected by these cancers. So think about African-Americans, right? Think about Hispanic communities, as well as Asians globally. So we need to identify better therapies. Still to this point, the 1-year overall survival for patients with this disease is extremely low. It's in the low range, along with pancreatic cancer and some of the other malignant cancers that we have to deal with.

ASCO Daily News: Well, following up on your point about developing better therapies for a wider group of patients, let's focus on disparities for a moment. One of the keynote speakers, Dr. Robert Winn, who is the cancer director at VCU Massey Cancer Center, reminded everyone that no matter how much progress is made in understanding cancer biology and developing new treatments, the impact of these treatments will be limited unless we address disparities in health care (). What are your thoughts about this?

Dr. Marcia Cruz-Correa: This is a topic that is very close to my heart. I am a Hispanic woman in science. I was born in the U.S. I'm an American citizen. But I see the differences that span across all different groups, based, unfortunately, not on the genes that you were born with, but rather on where you were brought up, the house that you lived in, the parents that you have, the exposures that you have, and lack of access, which is a huge barrier.

So as a physician scientist, you want to take into consideration how to really provide access, and how to understand the disparities. And I think Dr. Winn really explained it so eloquently. There is a phrase that I think maybe he was the one who coined it that is called the un-precision of precision medicine, right? So we continue to have all this technology, but then you realize that when you look at the data, the data comes from people that are mostly heterogeneous in certain regards, but mostly homogeneous to their racial and ethnic backgrounds.

So when you look at how common is a biomarker, and then you determine which agent to use in the patient that you have in front of you, it might be that particular biomarker is not even present. Not only that, if we cannot test patients because insurance doesn't cover it, because there are other barriers, or even you have a great drug, but then the insurance of your patient does not cover that. So it really highlights how sometimes, knowing more increases the disparities, right? So it's only great for a few, but not available for the masses.

And Dr. Winn has been a pioneer, making people alert, and he is involved in health policy. And he, as you very well expressed, was very eye-opening, right? He really confronted us with that disparity that exists, even in the best science that we know nowadays. So when you put that into the context of the conference--the theme of disparities and differences and diversity--there were abstracts that focused on groups that came from different backgrounds.

There were abstracts that evaluated prevalence of diseases according to diverse backgrounds. And one of the aspects that I love about the GI [meeting] is that we really from the beginning, not only looked at the science, but we also engaged investigators and scientists across the world that were looking at diseases that affected people from different parts of the world, and that highlighted the importance of understanding the genes--how are they present according to diverse populations?

And I mentioned at the beginning that there is an heterogeneity in the presence of biomarkers in tumors. But you have to also think that if we don't even test the patients that come from diverse backgrounds, how would you be able to know that? And compound that with the fact that depending on the exposures that are present in the life of a patient--the life of a human being--even the modification of those genes that you're born with are affected.

So because of epigenomics, we could see differences that are actually not based on the germline--on those genes that you're born with--but rather, are based on the exposures. And the response to therapy might completely be different. It might differ based on that particular genetic and epigenetic background.

And of course, I love the whole biomarker field, but things that are extremely more important and more relevant, such as access to this technology, come into play. And I think health policy needs to follow at the same pace of science. Because science is the driver of knowledge, but knowledge without being applied to the community--without being available to everyone--it becomes the biggest disparity. Because knowing but not doing is unacceptable.

ASCO Daily News: Well, there was very interesting research presented about microbiome and immunotherapy. Can you tell us about this?

Dr. Marcia Cruz-Correa: So microbiome research was one of the highlights also of this symposium. And we have been learning about how important is are gut microbiome in multiple diseases. So cancer is not an exception. And in fact, one of the abstracts that was presented, which is Abstract 161, they were looking at what was the particular microbiome composition of patients that had intestinal-type gastric cancer?

And I mentioned previously that gastric cancer is one of those cancers that disproportionately affect people from African-American ancestry and Hispanics, as well as Asian. And even in the U.S., when you look at the groups of patients that have gastric cancer, the difference between African-Americans and non-African-Americans is almost like three to one to have this disease. So trying to identify who will be able to respond to immunotherapy is key, because it will allow us to target the right population, and maybe even modify any factor that you could modify to help your patient to respond to the therapy.

So this Abstract 161, they evaluated over 400 patients that had gastric cancer. And what they were able to identify was that patients that had a microbiome diversity that was more rich, or those that responded to nivolumab, the anti-PD-L1, compared to those patients that didn't respond to the anti-PD-L1. And when they tried to identify what type of microbiome was that one that was almost predictive of response to therapy, they noticed that a specific group that was really important in the epithelial cell pathway were those that were more commonly present among patients that responded to the anti-PD-L1.

So as an gastroenterology and GI oncologist, you have to think immediately, can you change that microbiome? Can you give some sort of either a probiotic or an antibiotic to really enhance the response to immunotherapy? And there are studies that are already looking into that, so I think much more to come in this very exciting field of immunotherapy and the microbiome.

The other article I wanted to also highlight was the--let me see if I remember the number. Yeah, Abstract 11. And this is by Dr. Tenna Henriksen--T-E-N-N-A Henriksen. And it's very interesting, she's a PhD student at Aarhus University in Denmark. And this group of investigators presented very exciting data on the utilization of ctDNA as a biomarker for assessing response to therapy and prediction of who will have recurrence.

And let me put everyone in context, right? We're using now ctDNA, and we've been talking about this for the last few years. Before, we used to call this liquid biopsies, right? But now we know that liquid biopsies is almost like a genetic term. So ctDNA measures the amount of circulating tumor DNA.

And the company that they were using, it's a company from California that basically develops a personalized test based on the patient's tumor markers. So they use 16 top biomarkers that are present in the tumors. They could be mutations, oncogene mutations, or similar biomarkers. And they put together a personalized test for each individual.

And the investigators basically tested before the surgery. These were patients with colorectal cancer, stage 1 to 3. And then after surgery, they repeated the same blood test every 3 months. And what they were able to show was that when a patient had positive ctDNA, it predicted who was going to have a relapse by an average of 8 months before the imaging study showed that a patient had had recurrence.

So the way this study was designed, it was designed just as an observation translational study, meaning the data on the ctDNA was not available to the practicing or treating physicians, but rather, it was in parallel. But now we know that ctDNA has the capacity of providing very important information for the patient and the physician, where you will be able to determine who has a much higher risk for developing cancer. And think about the way that we practice medicine, right? This completely changes the paradigm.

We are not going to wait until we have the sickest cancer. The question is, will having this information in real life change the timing, for instance, of therapy? Will it change the timing for imaging? Will having this information and starting chemotherapy or immunotherapy earlier change the outcome for the patient? And all those questions are still unknown.

And it was great that we were able to see that it actually works. ctDNA works. But now we have to put it into the clinical practice context. So you are going to be seeing hopefully, in the next GI meeting, we all will be able to see more data. There are multiple studies that are really looking into how to integrate ctDNA, and they're being done in a randomized clinical trial fashion, and integrating this knowledge and randomizing people based on presence or absence of ctDNA after surgery.

So anyway, I am very excited about this data, and I'm hoping that we'll be able to integrate it and help our patients, right? And again, as we spoke at the beginning, it's key to have access to this new technology, and really help to disseminate the data, [by] including people from very different and diverse backgrounds in this clinical trial. So the U.S. Food and Drug Administration is really being adamant about inclusion, inclusion, and inclusion. And when a disease is over-represented in a community, there should be over-representation of that particular race, ethnicity, or community in the clinical trials that are developed for taking care of that particular disease.

ASCO Daily News: The COVID-19 pandemic has had a huge impact on health care. How did the meeting address the challenges of delayed cancer screenings and patients presenting with late stage disease, and COVID-19 vaccination for patients with cancer?

Dr. Marcia Cruz-Correa: I think COVID-19--everybody knows that it has changed the paradigm for the world, right? No longer--especially in the first few months--we were able to even do our regular job, right? We were really adapting to the new reality. And as recommended by the national authorities, like the Centers for Disease Control and many others, screening for cancer became a secondary activity.

So all the resources were really focused on the epidemic, the patients that were being diagnosed with COVID-19. So you can imagine that it created immediately a difference between what we were doing previous to COVID-19 and what we were doing after COVID-19. So all of a sudden we're screening for breast cancer, cervical cancer, colon cancer, lung cancer, or any of those which are highly common and preventable.

If you undergo screening, you might be able to diagnose early and prevent mortality. So that became part of--who is doing that? Nobody was doing that. I mean, it halted. So for a period of 3 or 4 months, the number of new cases diagnosed with any of those four cancers decreased dramatically, and there are several papers that highlighted that.

So we're starting 2021. We thought at the beginning that the whole COVID-19 pandemic will be over by now, right? That was wishful thinking. And now we know that ahead of us, it's another several months, even though we have the vaccine, right? But there's still a few months ahead of us that we're going to continue to be dealing with patients with COVID-19, and the morbidity and mortality associated to this disease.

So put this in the perspective of the medical and surgical oncologist, right? You are faced now with patients that most likely did not undergo screening. And estimates from experts in the field have pointed to the fact that that backlog that we have will really take months, if not years, to really be able to capture and do screenings in those populations. Because remember, every year, a new group of hundreds of thousands of patients become older, and they are required to have some sort of screening.

So this was one of the topics that was discussed. And I think the other one that's still a lot of unknowns is are patients that are immune-compromised, such as patients with cancer, able to mount the same immune response after you vaccinate them? Is there contraindication to receive a vaccination? Which vaccine is better?

And in fact, one of other keynote speaker--so we have two keynote speakers. One was Dr. Winn on the topic of cancer disparities, and then the other one was Dr. Hotez. He is from Baylor University in Texas ( And he's an expert in vaccines. He has been at the forefront of vaccination for many, many years, and of course now is part of the COVID-19 vaccine effort.

He talked about the different vaccines. And several people asked him, which vaccine do you think is better for patients that are immunocompromised? And his recommendation was that most likely, the mRNA vaccine, right? The Pfizer and Moderna are the ones that would be better. But there's so many unknowns, you know?

Even think about the gut microbiome. There's been now a few articles that have discussed whether or not COVID-19 changes the microbiome of people, and whether or not, according to the microbiome, the body will be able to modulate a better or worse response to COVID-19. So there are many more unknowns than knowns at this point.

However, the common discussion was that we need to push forward. We need to vaccinate our patients. And we need to be ready to ramp up the medical programs that we have to increase the capacity to start screening, right? So we have to take care of those that were not screened last year, and then take care of those that will need to be screened this year.

So we need to be on the lookout when this wave of new cancer shows up. And hopefully, health care systems will be able to ramp up their resources, and provide alternative ways of doing screening. I would say for colon cancer, can we move from less endoscopy-based screening to a more stool-based screening, which is readily available, noninvasive, and will allow us to screen faster.

ASCO Daily News: Absolutely. Before we wrap up the podcast, how do you feel the GI Cancer Symposium has moved the field forward? And is there anything else you'd like to add before we finish our discussion today?

Dr. Marcia Cruz-Correa: Thank you, absolutely. I mean, the GI meeting has been a pioneer in creating this convergence of four main organizations that work together to provide the best care for patients. When you think about a patient with GI cancer, none of us can do this by ourselves. And I think pioneers like ASCO that put together this amazing symposium- and of course, it's done in some of the other organs--have provided the ideal forum to have people that work together for the benefit of the patients.

And I have to tell you, since I was a fellow GI physician and a gastroenterologist by training, I remember the first time I heard about the GI meeting, I said, what is that? And then I saw the logos of the four organizations. And of course, as a gastroenterologist, I'm part of the American Gastroenterology Association as well. So I saw that, and I saw ASCO, and I said, wow, the premiere organizations joined together in one forum.

So I think it was pioneering. It was really a way of putting together experts, not only from the experts in the scientific field, but also in the clinical trial execution. And I think because of that, it is so important that we continue to promote the best science guiding therapies, and the best science guiding health policy. And diversity--we are a global community, where we see diversity across genomics, across social determinants, across cultural factors. And that all plays into what cancer is, and how to take care of our patients.

So I would like to finalize by really congratulating the organizations for working together, and demonstrating that when we put our resources together, rather than finding our differences as what type of physician or surgeon you are, or what type of organization, we really work together for our patients. And when we keep patients first and in front of us, we can work together looking into the future. And that's what the GI Cancers Symposium does.

ASCO Daily News: Beautifully, said, Dr. Cruz-Correa. And thank you very much for sharing some really interesting highlights with us today on the ASCO Daily News podcast.

Dr. Marcia Cruz-Correa: My pleasure.

ASCO Daily News: And thank you to our listeners for joining us as well. You will find links to all of the studies mentioned in today's discussion in the transcript of this episode. And if you're enjoying the content on the ASCO Daily News podcast, please take a moment to rate and review us wherever you get your podcasts.


Disclosures: Dr. Marcia Cruz-Correa

Leadership: AACR

Stock and Other Ownership Interests: Pan American Center for Oncology Trials

Consulting or Advisory Role: Exact Sciences

Patents, Royalties, Other Intellectual Property: Licencing agreement with Johns Hopkins University on technology.


Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care, and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.