2019 ASCO Annual Meeting Research Round Up: Gastrointestinal Cancers and Leukemia

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The 2019 ASCO Annual Meeting, held May 31 to June 4, brought together physicians, researchers, patient advocates, and other health care professionals from around the world to present and discuss the latest research in cancer treatment and patient care. In the annual Research Round Up podcast series, Cancer.Net Associate Editors share their thoughts on the most exciting scientific research to come out of this year’s ASCO Annual Meeting and what it means for patients. First, Dr. Jeffrey Meyerhardt will discuss 4 studies in gastrointestinal cancers, including 1 on colorectal cancer, 1 on gastric cancer, and two studies related to pancreatic cancer. Dr. Meyerhardt is the Douglas Gray Woodruff Chair in Colorectal Cancer Research, Clinical Director and Senior Physician at the Gastrointestinal Cancer Center at the Dana-Farber Cancer Institute, Deputy Clinical Research Officer at the Dana-Farber Cancer Institute, and Professor of Medicine at Harvard Medical School. He is also the Cancer.Net Associate Editor for gastrointestinal cancers. Dr. Meyerhardt: My name's Jeff Meyerhardt. I'm a gastrointestinal medical oncologist at the Dana-Farber Cancer Institute in Boston, Massachusetts. Today I'm going to discuss research on gastrointestinal cancers that were presented at the 2019 ASCO Annual Meeting. And let's talk about four studies: 1 in colon cancer, 1 in gastric cancer, and 2 studies related to pancreatic cancer, all of which are going to affect how patients are treated in the upcoming years. Starting with the studies on colon cancer, there were 2 additional studies looking at the duration of adjuvant therapy for colon cancer. Adjuvant therapy is the chemotherapy that's given after surgery for people who had a resection of their colon cancer that didn't have evidence of metastases. We give adjuvant therapy to try to prevent and reduce the risk of recurrent disease. The standard of care up till a few years ago was to give 6 months of adjuvant therapy. And for most patients who had stage III or lymph node positive disease, that was 6 months of a fluoropyrimidine, either 5-FU, or an oral form capecitabine with oxaliplatin. This was also given to some patients who have higher-risk stage II disease. Two years ago at ASCO, we learned that giving 3 months of therapy was sufficient, or what we'd describe as non-inferior, for some patients who have stage III colon cancer, particularly those who had what would be considered a better-risk stage II colon cancer, and actually particularly if they got a particular regimen of combining capecitabine and oxaliplatin. At this year's ASCO, there was a study looking at patients with stage II disease. Most of them had higher-risk stage II disease, something where they didn't have positive lymph nodes, but some other feature that made you a little bit more worried that there was a relatively higher-risk of recurrent disease. And the findings were essentially very similar to what we saw for stage III disease; that for some patients, 3 months of treatment was adequate, particularly if you gave capecitabine/oxaliplatin, and had less toxicity than 6 months of therapy. But if you gave 5-FU/leucovorin/oxaliplatin, a regimen called FOLFOX, 6 months of treatment was necessary. These studies add to the conclusion that first, we can't treat all colon cancers in the adjuvant setting the same, that we should think of them as risk adjustment, and we also have to make decisions regarding what type of treatment, which will help determine the duration of therapy. The next study I'm going to focus on is looking at gastric cancer and looking specifically at the role of immunotherapy. So what we've already known is that patients who have gastric cancer and esophageal cancer can benefit from immunotherapy in later-line therapy, so after an initial first-line or second-line chemotherapy is no longer helping a patient or is too toxic to continue. The study that was presented at ASCO this year, what is called the KEYNOTE-062 study, was actually looking at 3 different arms of therapy. One was giving a drug pembrolizumab, one of the immunotherapies alone. The second arm was giving chemotherapy alone. And the third arm was giving pembrolizumab with chemotherapy. In looking at what would be the best strategy for patients who are initially being treated for metastatic gastric cancer. They specifically looked at patients where we think there may be a higher chance of activity. So there are certain ways to look at the tumor and score what's the potential in immunotherapy would be helpful. And this is what's called the CPS score. Patients who had had a CPS score of at least 1, and they also broke it down for people that had even a higher score, greater than 10, in the analysis. And what they found is compared to doing standard chemotherapy, in this case, of fluoropyrimidine, 5-FU, or capecitabine with a platinum, cisplatin, giving pembrolizumab could be non-inferior in terms of overall survival for patients as initial therapy for metastatic gastric cancer; that they saw that in patients who had a CPS score greater than 1. They showed actually that it was superior to give pembrolizumab in terms of overall survival if the CPS score was greater than 10. What is a little curious in this study is that progression-free survival, which is how long it takes until you have to switch to therapy, wasn't actually better with pembrolizumab compared to chemotherapy for the people who had relatively lower CPS scores. But it was non-inferior for those who had a greater than 10. The second part of the study was looking at should we give chemotherapy and pembrolizumab at the same time, like the whole kitchen sink, at the same time of both giving chemotherapy and an immunotherapy. And that actually didn't add any benefit to chemotherapy alone. So it was not improvement in overall or progression-free survival. So what do we conclude from KEYNOTE-062? Well first is that there are some patients where giving an immunotherapy upfront by itself can be just as good as starting chemotherapy, particularly those who have a score that's a relatively higher likelihood of benefiting from immunotherapy. But we also learned that combining them together does not add extra bang for the buck as initial treatment. There should still be a therapy considered later, whether you start with pembrolizumab and then later get chemotherapy or vice versa. But doing them all at the beginning does not seem to add additional benefits. There were then 2 studies of note for pancreatic cancer. One of them was an adjuvant study, which again, adjuvant therapy is giving chemotherapy after surgery to try to reduce the risk of recurrent disease. What we know for pancreas cancer, there are several options to consider in terms of adjuvant therapy after surgery. For quite a few years now, the standard was giving a drug called gemcitabine. There was then a study looking at gemcitabine with an oral drug called capecitabine, again, the oral form of 5-FU, and that looked to be a little better than gemcitabine alone. And then several years, a study from the Canadian Cancer Treatment Group and then a Unicancer GI PRODIGE Group looked at a combination of folfirinox, a 4-drug regimen that's now very standard for some patients with metastatic pancreas cancer. In looking at that regimen as adjuvant therapy, compared to gemcitabine alone, that study showed a real significant improvement in terms of recurrence rate and disease-free survival for patients who got this 4-drug regimen compared to gemcitabine alone, and has really become a standard for patients who have a good performance status after their surgery. The current study that was presented at the 2019 ASCO Meeting was looking at a different combination, looking at gemcitabine plus another drug called nab-paclitaxel. It's a combination also used in metastatic pancreatic cancer. It was shown to be better than gemcitabine by itself in metastatic pancreatic cancer. And the hope would be another option for patients in the adjuvant setting. Unfortunately, the study fell a little short in terms of the primary endpoint as initially determined when the protocol was being developed, what was called an independent assessment of disease-free survival. So sending the scans and sending all the data to independent reviewers, and that again just fell a little short statistically. If you look at investigator-assessed disease-free survival, it actually was statistically significant, as well as overall survival. The conclusion for the study is even though it didn't quite meet the mark in terms of what was predefined, it does give suggestion that it is better than giving gemcitabine alone. And there are patients in the adjuvant setting for pancreas cancer where folfirinox is probably not as good of an option: it's a fairly toxic regimen. People who have a performance status having a little more difficulty recovering from the surgery or have more comorbidities, gemcitabine plus nab-paclitaxel probably still should be considered an option for these patients, compared to gemcitabine alone. The final study, which led to a plenary session, which is basically one of the 4 most attractive abstracts in the 2019 ASCO Annual Meeting this year, was looking at maintenance therapy for people with metastatic pancreatic cancer using what's called a PARP inhibitor olaparib. It was specifically for patients who had received a platinum-based chemotherapy and they had a germline mutation of BRCA. So BRCA mutations are commonly known to affect the risk of developing breast and ovarian cancer. There are 2: BRCA 1 and BRCA 2. Those also have association with increased risk of pancreatic cancer. And what we know is the PARP inhibitor, through what are called DNA repair mechanism, do seem to have activity in these various type of cancers, including for patients with metastatic pancreatic cancer. This was specifically looking at people who had metastatic pancreatic cancer. Could you get them off the more cytotoxic chemotherapy for a period of time to do something more of what would be considered a maintenance therapy. So having them for period time off toxic therapy and not impacting their overall outcome. It ends up about 4 to 7 percent of metastatic pancreatic cancer patients harbor a BRCA mutation. What we know about BRCA-mutated pancreatic cancers, they have an increased benefit from a platinum-based chemotherapy, cisplatin or oxaliplatin, so patients had to have had a platinum-based therapy to go on the study. They were on chemotherapy for at least 16 weeks and then they were randomized to stop their chemotherapy and receive elaborate versus placebo until there was disease-free, disease progression, or increased toxicity. And what we saw is that the progression-free survival, the time till they had to restart chemotherapy, actually was doubled with the group receiving the maintenance therapy with olaparib. So that was really an exciting finding and a really important finding where you can get people off of chemotherapy for a period of time until you have to restart chemotherapy. Now there is not a survival benefit that was noted yet on the study. It is still very early to look at overall survival. There are also patients who are able to crossover in terms they got olaparib, another part in their cancer treatment, because of the known benefit in metastatic disease. So overall survival may be a little harder to fully interpret, but I do think that this will become a standard for patients with BRCA-mutated colorectal cancers, to receive chemotherapy for some period of time, several months, and then if they're doing well, then to switch them to a maintenance therapy. So that is our summary of the GI cancer research from the 2019 ASCO Annual Meeting. Again, my name is Jeffrey Meyerhardt, and thank you for listening. ASCO: Thank you, Dr. Meyerhardt. Next, Dr. Guillermo Garcia-Manero will discuss a study on a new immunotherapy drug that offers promising results in patients with acute myeloid leukemia or myelodysplastic syndromes, as well as 2 additional studies that looked at t-cell therapies. Dr. Garcia-Manero is the Deputy Chair of Translational Research and Professor, Department of Leukemia, at The University of Texas MD Anderson Cancer Center in Houston, Texas, and the Chief of the Section of Myelodysplastic Syndromes at MD Anderson Cancer Center. He is also the Cancer.Net Associate Editor for Leukemia. Dr. Garcia-Manero: Hello. I am Guillermo Garcia-Manero. I am a professor in the Department of Leukemia at the University of Texas MD Anderson Cancer Center. I'm very happy to summarize some of the key presentations at this year's ASCO meeting in Chicago. Of course, ASCO is big on solid tumor malignancies, but there is more and more information regarding leukemia treatment for our patients, also, at the meeting. This year, there were a number of very interesting presentations. First, I want to start briefly saying that there was a very interesting educational symposium where Drs. Al-Kali, Sekeres, Craddock, and myself discussed how to use these hypomethylating agents, drugs like azacitidine or decitabine in patients with leukemia. This meeting was very well attended by multiple community physicians that attend ASCO, and it contained, I think, very useful information in terms of the use of these compounds for our patients. In terms of research presentations, there were multiple. The one that I actually felt was perhaps more interesting was a presentation by Dr. Sallman from the Moffitt Cancer Center in Tampa where he was describing the first results of a new therapy for patients with MDS and AML and potentially other hematological malignancies and cancers known as Hu5F9-G4. This agent is an antibody that targets a molecule called CD47. This was discovered by Dr. Maute and Dr. Weissman at Stanford. It is known to be a “don’t eat me” signal in a way kind of an alternative immune checkpoint inhibitor type of process. But this is interesting because it's focusing more around macrophages more than lymphocytes and it could have a broad use, again, not only in leukemia and hematological malignancies but potentially many other cancers. I think that this data is very striking because the results of Dr. Sallman indicate a very high level of activity with the combination of the hypomethylating agent azacitidine, in this case, both in MDS and AML. This was agnostic of molecular and cytogenetic alterations. It was well tolerated, although there was a little bit of anemia early on with administration of this therapy. But I think this was one of the most innovative and promising new potential therapies for our patients with leukemia. This drug has been shown to be active in lymphoma and now, we expect that the studies initially done in the UK and in Tampa are going to be expanded to other centers in North America, and they may actually provide with a very interesting innovative and very active new form of therapy for our patients. So I thought that was the most innovative presentation at the ASCO meeting. Of course, there were multiple other presentations. There was additional data on new FLT3 inhibitor known as gilteritinib. This drug recently approved for patients with AML. There was also further information on a new compound known as CX-01 for patients with acute myelogenous leukemia. Again, this is an interesting compound that seems to be a heparin analog, and the early studies are showing significant activity as well for our patients. There was also very interesting data in terms of the phase I results of the ZUMA-3 trial. This is a CAR T-cell type of approach for refractory patients with acute lymphocytic leukemia. And finally, this interesting presentation from the MD Anderson group with an off-the-shelf viral-specific T-cell therapy against patients with adenovirus disease that are immunosuppressed. It's actually very important in a way-- kind of similar therapies for patients that have viral complications, this group have shown, actually, significant activity of similar type of approaches for patients with BK virus and other conditions. So in summary, I think that the meeting was very important like it is every year. I think that we're starting to see presentations at ASCO for new agents of high relevance. I think that the community, at least in MDS and AML, it is very interested on the follow-up with the Hu5F9-G4 agent in combination with AZA for MDS and AML. And we're looking forward to be part and see the results of expanded phase II and potential phase III studies with this compound. And with that, I want to thank you for your attention. ASCO: Thank you Dr. Garcia-Manero. Learn more about these topics and other research presented at the 2019 ASCO Annual Meeting at www.cancer.net, including additional Research Round Up podcasts. And if this podcast was useful, please take a minute to subscribe, rate, and review the show on Apple Podcasts or Google Play. This Cancer.Net podcast is part of the ASCO Podcast Network, a collection of 9 programs covering a range of educational and scientific content offering insight into the world of cancer care. You can find all 9 shows, including this one, at podcast.asco.org. Cancer.Net is supported by Conquer Cancer, the ASCO Foundation, which funds breakthrough research for every type of cancer, helping patients everywhere. To help fund Cancer.Net and programs like it, donate at conquer.org/support.