ASCO20 Virtual Scientific Program Research Round Up: Leukemia, Colorectal Cancer, and Lung Cancer

ASCO: You’re listening to a podcast from Cancer.Net. This cancer information website is produced by the American Society of Clinical Oncology, known as ASCO, the world’s leading professional organization for doctors who care for people with cancer. 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. Cancer research discussed in this podcast is ongoing, so the data described here may change as research progresses. Every year, the ASCO Annual Meeting brings together attendees from around the globe to learn about the latest research in the treatment and care of people with cancer. This year, a record 42,750 attendees from 138 countries worldwide gathered virtually for the ASCO20 Virtual Scientific Program, held Friday, May 29 through Sunday, May 31. In the annual Research Round Up podcast series, Cancer.Net Associate Editors answer the question, “What was the most exciting or practice-changing research in your field presented at the ASCO20 Virtual Scientific Program?” In this first episode, 3 editors discuss new research in the fields of leukemia, colorectal cancer, and lung cancer. First, Dr. Jessica Altman will discuss 2 studies in myelodysplastic syndromes and acute myeloid leukemia. Dr. Altman is Associate Professor of Medicine in the Hematology Oncology Division at the Feinberg School of Medicine, Northwestern Medicine. She is also the Cancer.Net Associate Editor for Leukemia. View Dr. Altman’s disclosures at Cancer.Net. Dr. Altman: Hi, everyone. My name is Jessica Altman. I am a leukemia physician at Northwestern Memorial Hospital in Chicago, and I am pleased to talk today about some interesting studies that were presented at ASCO 2020 and really use that as a marker of the excitement that is ongoing in the field of myeloid malignancies. In both myelodysplastic syndrome and acute myeloid leukemia, there have been a lot of novel therapies that have been recently approved, and other agents that are currently ongoing in a clinical trial. I think it's important for me to mention that the studies that I will be discussing today, I do not have any direct conflicts of interest, but I am involved with the development of other novel therapies. I'll be talking about two studies today. The first one is a clinical trial, and the second one is a palliative care study that was conducted. The first study that I would like to discuss is the study presented in an oral session at this year's ASCO presented by Dr. David Sallman on behalf of his group at Moffitt and a large clinical trial network of other investigators. They studied the combination of a novel agent called magrolimab, which I'll mention more in a moment, in combination with a standard lower-intensity chemotherapy called azacitidine. This is studied for the treatment of high-risk myelodysplastic syndrome and acute myeloid leukemia. Magrolimab is an antibody that blocks something called PD47, which is a macrophage immune checkpoint and essentially a signaling cancer that says, "Don't eat me." And this antibody allows the engulfment or destruction of tumor cells and also is able to eliminate the really deep stem cells that cause the development or maintain the leukemia and MDS. So in this study, the investigators conducted a trial of azacitidine in combination with magrolimab, and they treated a handful of patients with both myelodysplastic syndrome and acute myeloid leukemia. And what they found was that the combination therapy was both well tolerated and resulted in a better-than-anticipated response rate. So better than what we would anticipate with a low-intensity chemotherapy alone. In particular, they found a nice response rate in individuals whose leukemia or MDS expresses a specific mutation. That mutation is called TP53, and that mutation has been associated with a poor chance of response to the available therapies and particularly a short duration of response. This trial is particularly exciting to me because it demonstrates the ability to combine novel therapies with lower-intensity treatments and allows what we hope for will be a higher chance of response. This is with a relatively limited study, and further trials in this space involving this agent and combination are planned and are ongoing. There are other agents that are also targeting the TP53 mutation, and those are things to watch out for as well. I'd like to move on to a supportive care study that was presented as well. This was a study that was presented by Dr. El-Jawahri, and funded by the Leukemia and Lymphoma Society. This is a study that looked at patients with acute myeloid leukemia receiving intensive chemotherapy. The relevance and importance for the study is because supportive care trials, and particularly looking at palliative care in general in acute myeloid leukemia have not frequently been done to date. And the background for this study is that individuals with acute myeloid leukemia frequently can experience decline in their quality of life and mood during their hospitalization for induction therapy. And it is not uncommon for adults with acute myeloid leukemia to receive aggressive care at the end of life. So this group sought to examine the effect of an integrative palliative and oncology care and affect quality of life, mood and symptoms associated with things like post-traumatic stress and with a huge emphasis on end-of-life outcomes. And what this group found was that the integrative palliative and oncology care model for patients with acute myeloid leukemia receiving intensive chemotherapy led to improvements in patients' quality of life, their psychological distress and the care at the end of life. And the investigators asked for consideration of palliative care as a standard of care for all adults with acute myeloid leukemia, from really thinking about the incorporation of palliative care model, from diagnosis and throughout treatment and not just reserving that to the end of life. Thank you for your time. I was very excited with the numerous clinical trials in the myeloid neoplasm space presented at this year's ASCO. And the work that was presented is really a marker of how much excitement there is that's ongoing in this field. Thank you. ASCO: Thank you, Dr. Altman. Next, Dr. Jeffrey Meyerhardt will discuss 4 studies in colorectal 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. View Dr. Meyerhardt’s disclosures at Cancer.Net. Dr. Meyerhardt: Hi my name's Jeff Meyerhardt from the Dana Farber Cancer Institute in Boston, Massachusetts. I'm going to speak about some of the key abstracts that were presented at this year's virtual ASCO meeting in 2020. I have no pertinent disclosures related to the abstracts I'm going to discuss. So the first and probably the most prominent and abstract, which was presented in the plenary session, was a study called KEYNOTE-177. It was a study specifically for patients with a certain subtype of metastatic colorectal cancer, what's called microsatellite unstable tumors. It's a way that colorectal cancers first emerged when they developed from normal cells to abnormal cells. It only constitutes about 3 to 5 percent of metastatic colorectal cancers. But we know a lot about those cancers because some of them are related to inherited conditions and some are not related to conditions, but they land up at those other cancers that seem to be much more susceptible to immunotherapy. And in fact, they're the ones that immunotherapy indicated for in terms of colorectal cancer. And so the study that was presented was comparing patients receiving what's called a checkpoint inhibitor and a type of immunotherapy, in this case, pembrolizumab, to standard chemotherapy. So chemotherapy that we would typically give as initial treatment for metastatic colorectal cancer. Currently, the indication with the FDA is that patients would receive immunotherapy later as a later line of therapy, if other things weren't working and this was really to say, should we be giving it much earlier on? So as a randomized trial, it was about 300 patients and they compared starting just with an immunotherapy, pembrolizumab versus chemotherapy and either a drug called bevacizumab or a type of a another inhibitor called an EGFR inhibitor, cetuximab.  And it lands up starting with the pembrolizumab had a real significant improvement in progression free survival. It was a comparison of actually 8.2 months with standard treatments, which is what we see in a lot of trials versus 16.5 months. That's essentially for the times we had to switch to different therapy and all these other endpoints were also met in terms of a 12-month and two years of progression free survival. It was a statistically significant event, and it really will change practice for that subpopulation of patients with metastatic colorectal cancer. What's still really important is to try to figure out for the rest of the patients how immunotherapy can benefit them. And that unfortunately, we don't have as much data yet. Another abstract presented this year at ASCO was a sort of update of what's called the BEACON trial, and this is, again, another subgroup of colorectal cancers, colorectal cancers that have a particular mutation in them, what's called a BRAF mutation. We know that occurs in somewhere between 5 and 10 percent of colorectal cancers. They can sometimes be a more aggressive cancer and there were multiple drugs that have been tested in multiple combinations of those drugs over the past 10 years, but the largest effort was really looking at trying to give patients a standard treatment to combining a BRAF inhibitor, in this case, encorafenib, which is an oral pill, with an EGFR inhibitor called cetuximab and also potentially adding a third drug, binimetinib, which is called a MEK inhibitor, also an oral pill. And the study, the BEACON study, which was a large international randomized study compared those three arms. The main comparison was saying, should you have two drugs compared to control or three drugs compared to control, control being standard treatment. And looking at both of those compared to standard treatments. They weren't actually meant to compare the two to three drug and initially the results suggest that three drugs was optimal. But the study that was presented at ASCO and ultimately actually led to the actual FDA approval, is using a two drug combination. So encorafenib and cetuximab, which again was better than control and really becomes the standard for later line treatment of BRAF mutated colorectal cancer. We don't know if that should be the initial treatment. That study is now about to get started to say, "Should we start with BRAF directed therapy?" but we know that if you had progressed in other standard treatment, that is certainly an option that should be considered. There were two studies that looked at adjuvant therapy for colon cancer. Adjuvant is after someone has surgery and then they receive chemotherapy to reduce their risk of recurrence, one of them was a follow up to an effort to look at how many months of adjuvant therapy is necessary. This was called the IDEA collaboration. It was an international effort that included 14000 patients randomized to three months of treatment versus six months of treatment. And what we learned from that is for patients, particularly, who have a better risk tumor. So they all have stage III disease. Meaning they had surgery, the pathology showed some lymph nodes in the sample, but they didn't have evidence of metastatic disease at the time when they were diagnosed and those patients that they received three months of therapy if they only had one to three positive lymph nodes or not all the way through the bowel wall. Three months of therapy seemed to be just as good as six months, particularly when you do a combination of oral drug capecitabine with an IV medication called oxaliplatin and those with higher risk disease, those patients should probably receive six months, though in some cases, three months also seems to be sufficient. And this was a follow up to show that actually overall survival also was not inferior to do three months versus six months in those patients who have better risk disease or with capecitabine and oxaliplatin. The second adjuvant trial was one that I actually led. It was a large trial that was run through the National Cancer Institute. It was looking at standard chemotherapy in stage III colon cancer, same population I just discussed, and whether adding celecoxib, which is what's called a Cox-2 inhibitors. It's kind of like aspirin, a little bit more specific. And then there was a lot of data that those type of drugs could be helpful in patients to reduce polyps and may potentially be beneficial in patients who already had colorectal cancer. So we conducted a large clinical trial, comparing standard chemotherapy with the celecoxib or standard chemotherapy alone. And unfortunately, adding the celecoxib didn't actually add any statistically significant benefit. There was a slight improvement, but it wasn't statistically significant. So it is a negative study and unfortunately does not move the field in terms of improving outcomes for patients with stage 3 colon cancer. There are still some ongoing studies, specifically looking at aspirin that we await to see if that would make a difference in outcomes. So those are some of the highlighted studies focused on colon and colorectal cancer from ASCO this year. Thank you very much. And again, my name's Jeff Meyerhardt from the Dana Farber Cancer Institute. ASCO: Thank you, Dr. Meyerhardt. Next, Dr. Jyoti Patel discusses 3 studies in non-small cell lung cancer. Dr. Patel is the Medical Director of Thoracic Oncology and Assistant Director for Clinical Research at the Lurie Cancer Center of Northwestern University. She also serves as Associate Vice Chair for Clinical Research in the Department of Medicine. She is also the Cancer.Net Associate Editor for Lung Cancer. View Dr. Patel’s disclosures at Cancer.Net. Dr. Patel: Hi. My name's Jyoti Patel. I'm a professor of medicine at Northwestern University and associate editor of Cancer.Net for lung cancer, and I'm going to talk about some of the most exciting lung cancer abstracts that were presented at the 2020 ASCO Annual Meeting. One of the most important and, I think, impactful to patients and practice-changing studies was actually selected as a plenary session abstract, and plenary abstracts are those that are rated the highest of all of the thousands of abstracts that are submitted, so whenever there's one in our particular disease site, we're always really excited, and we've been waiting for this ever since we heard from a press release that a positive study on lung cancer was going to be presented. The study was called the ADAURA study. And the ADAURA study was sponsored by AstraZeneca, and I have worked as a consultant for AstraZeneca in the past.  So the study was looking at a drug called osimertinib, in patients who had early-stage lung cancer which was surgically resected. So as we know, a minority of patients, unfortunately, have stage I and stage II lung cancer, and about 30% of patients have stage III lung cancer. For many of these patients, surgery is the primary modality, and we do surgery with curative intent. However, despite doing surgery, there is a significant chance that the cancer can recur. So the study was looking at osimertinib as adjuvant therapy in patients with resected lung cancer. Osimertinib is an EGFR tyrosine kinase inhibitor. It's a targeted therapy that blocks the EGFR protein, which is often mutated in patients with lung cancer. So osimertinib is the treatment of choice for patients with advanced lung cancer that harbor an EGFR mutation. That mutation occurs in about 15% of American patients, and higher proportions of patients in some parts of the world. These patients, early on, had surgery, and then they were found to have an EGFR mutation, and then they were randomized to either three years of osimertinib as a daily tablet, versus a placebo, and the endpoint of this study was disease-free survival, so that's the length of time until there's evidence that the cancer has recurred. In this study, taking osimertinib significantly reduced the chance that the cancer would return within those three years, and the magnitude of benefit was highly significant. So with higher stages of disease, the likelihood that the cancer could come back is higher, and so the benefit was greatest in patients with stage 2 and stage 3 disease, and in fact, in patients with stage 3 disease, it decreased the recurrence rate by almost 85%. So really, really significant and impactful to our patients. Some people have questions about whether this should now be a standard of care, because we're not really showing whether we're improving the overall survival of patients. Many oncologists, myself included, think that survival with no evidence of disease is really meaningful for patients. It's going to be important, as the study matures, to see what the overall survival data look like, but in the three years of taking the drug, which is relatively well tolerated, the survival benefits, to me, translates to better quality of life, return to function and work, and staying away from catastrophic complications of cancer recurrence, like cancer coming back in the brain, or in the bone, and really impacting quality of life. And the next study I want to discuss is a study looking at immunotherapy and chemotherapy in patients with non-small cell lung cancer. So the study is called 9LA. It's a CheckMate trial, so BMS studied their drugs nivolumab and ipilimumab in combination with chemotherapy. My institution has received research funding from BMS for the study of nivolumab and ipilimumab, and I've served as a consultant in the past. In this study, patients who were treatment-naive, so hadn't received prior therapy, were randomized to either chemotherapy, which was an older standard, admittedly, versus a combination of a short course of chemotherapy, so only for six weeks, in combination with the immunotherapies nivolumab and ipilimumab. The rationale for giving chemotherapy with immunotherapy is multifold. So one is that chemotherapy kills cancer cells, and in doing so, it releases neoantigens, or proteins, that might make the immunotherapy more effective. It sort of targets these cells as foreign, and it kind of helps amp up the immune system. It also sort of decreases the cancer burden, and we know that immunotherapy tends to be more effective when there's fewer sort of volumes of cancer to treat. So this was a really interesting design, and impactful because the chemotherapy is given for such a short course, so the ongoing toxicities of chemotherapy over several months, it sort of goes away. So less fatigue, less lowering of blood counts. The study was looking at overall survival, and the study was positive, and this led to an FDA approval in May. The study showed that, in the initial time in which chemotherapy and immunotherapy were given, patients did quite well, and then they sort of plateaued, and at 12 months, almost two-thirds of patients were on the immunotherapy, compared to about half of patients which were on chemotherapy. And so that was significant. Although these results are comparable to other treatment options we have with ongoing chemotherapy and immunotherapy, are in patients with really high PDL numbers of immunotherapy alone, I think this trial is important for patients because it offers a different alternative. Having a short course of chemotherapy may make a lot of sense for patients. The cumulative toxicity from chemotherapy, it can't really be understated. Although our chemotherapies are better tolerated than ever before, the idea of just six weeks of chemotherapy and then going into immunotherapy, I think, is really an attractive one, and may give us options from multiple other treatments down the line. So I think this is important for patients. I think it certainly makes life a little bit more complicated for medical oncologists because now we have multiple options to discuss with patients, but at the end of the day, that's the best way we can personalize therapy for our patients, really taking into account overall disease status, as well as patient preferences, and tolerance of toxicities, and aims in the future. The last study that I want to highlight is a study called the DESTINY study. I don't have any disclosures for this study. This study was looking at a subgroup of patients with lung adenocarcinoma with HER2 mutations. So there have been a lot of targeted therapies that have gained our attention and FDA approvals in the past couple of years, and it's really exciting. We're understanding that development of targeted therapies is based on early assessment of mutations in our patients, and we have a host of mutations, now, with FDA approved drugs. Just in May, drugs targeting RET, or R-E-T fusions was approved. Another drug targeting MET exon 14 skipping mutation was approved. HER2 mutations represent a subset of patients, a small subset of patients, about 2% of lung cancer patients, and they've been really difficult to treat. We know about HER2 because it's often a target for breast cancer, but in lung cancer, it's often a small mutation that causes activation, that causes the cells to grow. We haven't had a lot of really great options for these patients, and although there are multiple drugs in development, this particular trial gained a fair bit of attention because it looks quite promising. So this study was looking at trastuzumab deruxtecan, and that's an antibody-drug conjugate. So the idea is it's an antibody that binds to HER2-- which is on cancer cells. When it binds to that target, the drug conjugate, or the payload, is released into the cancer cell. So there's less toxicity. It's a targeted therapy with very sort of directive toxin to the cancer cells. There are a number of antibody-drug conjugates in development, and some are FDA approved for other indications. In this study - it was a single-arm study - patients with HER2 mutations received the antibody-drug conjugate, and they saw a really significant response rate. Almost all patients had some disease diminution, some response, with about 60% of patients having what we call a partial response, a 30% reduction in tumor cells. What was also exciting was that some patients have been able to show that their responses are quite durable, and so the disease control has lasted. Certainly, this is an early trial. Only about 39 patients were treated. So we look forward to further studies of this compound, but finally, it's nice to have something that looks this promising in this particular patient population. ASCO: Thank you, Dr. Patel. Learn more about the research presented at the ASCO20 Virtual Scientific Program at www.cancer.net/blog, and subscribe to Cancer.Net podcasts on Apple Podcasts or Google Play for additional episodes in the Research Round Up series, released throughout the summer. This Cancer.Net podcast is part of the ASCO Podcast Network. This collection of 9 programs offers insight into the world of cancer care, covering a range of educational, inspirational, and scientific content. 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/donate.