2023 Research Round Up: Breast Cancer, Lymphoma, Multiple Myeloma, and Brain Tumors

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The theme of the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting was “Partnering With Patients: The Cornerstone of Cancer Care and Research.” From June 2 to 6 in Chicago, Illinois, and online, cancer researchers and clinicians from around the world gathered to discuss the latest cancer research and how to ensure that all people receive the cancer care they need. In the Research Round Up series, members of the Cancer.Net Editorial Board discuss the most exciting and practice-changing research in their field presented at the meeting, and explain what it means for people with cancer. In today’s episode, our guests will discuss new research in breast cancer, lymphoma, multiple myeloma, and brain tumors. First, Dr. Norah Lynn Henry discusses new research in early stage and metastatic breast cancer. Dr. Henry is Professor and Interim Chief of the University of Michigan's Division of Hematology/Oncology in the Department of Internal Medicine and the Breast Oncology Disease Lead at the Rogel Cancer Center. She is also the 2023 Cancer.Net Associate Editor for Breast Cancer. You can view Dr. Henry’s disclosures at Cancer.Net. Dr. Henry: Hi, I'm Dr. Lynn Henry, a breast cancer oncologist from the University of Michigan Rogel Cancer Center. Welcome to this quick summary of the most exciting new research in breast cancer that was presented at the 2023 ASCO Annual Meeting. I have no conflicts of interest for any of the trials that I will talk about. First, I'm going to give a very brief overview of the types of breast cancer, then talk about some research that was presented on both early-stage and metastatic breast cancer. As a reminder, there are multiple kinds of breast cancer. Some breast cancers are called hormone receptor-positive or estrogen receptor-positive and are stimulated to grow by the hormone estrogen. We treat those cancers with anti-estrogen or anti-endocrine treatments, which block estrogen or lower estrogen levels. Other breast cancers are called HER2-positive. These are often more aggressive cancers. But because they have extra copies of HER2, they often respond to treatments that block HER2. Finally, there are breast cancers that don't have hormone receptors or HER2. These are called triple-negative breast cancer and are also often aggressive cancers. Most of the results I'm going to highlight today are treatments for estrogen receptor-positive and HER2-negative breast cancer. One of the main stories from the ASCO Annual Meeting was the result of the NATALEE trial. At the present time, for patients with estrogen receptor-positive, HER2-negative early-stage breast cancer who were at high risk of having their breast cancer come back, the currently recommended treatment is anti-endocrine therapy. Based on the results of a prior trial called monarchE, we also consider adding a medicine called abemaciclib, which turns off some enzymes in the cell that are called CDK4 and CDK6, which are known to make estrogen receptor-positive breast cancer cells grow. Abemaciclib can further reduce the risk of cancer recurrence compared to endocrine therapy alone, but it does have some side effects, most commonly, diarrhea. In the NATALEE trial, which was presented for the first time at this ASCO meeting, researchers studied a similar type of medication called ribociclib. It acts similarly to abemaciclib, although it is more likely to cause low blood counts and less likely to cause diarrhea. Ribociclib is currently routinely used in combination with anti-endocrine therapy to treat patients with metastatic estrogen receptor-positive breast cancer but is not yet routinely used in the early-stage setting. In the NATALEE trial, patients with estrogen receptor-positive, HER2-negative early-stage breast cancer who are at high risk of breast cancer recurrence were enrolled. Half the patients were treated with just standard anti-endocrine therapy and half also received ribociclib for 3 years. After the 3-year treatment period, those who received both ribociclib and anti-endocrine therapy were about 25% less likely to have their cancer come back compared to those who received only anti-endocrine therapy. Overall, the medication was quite well tolerated. It is important to note that this drug is not yet FDA-approved in the setting. The remaining trials I will highlight are for treatment of metastatic breast cancer. There were many trials examining how best to use drugs that we are actually already using in the clinic. For example, many presentations were about the CDK4/6 inhibitors that I just mentioned. Typically, patients who have just been diagnosed with estrogen receptor-positive, HER2-negative metastatic breast cancer get treated with anti-endocrine therapy plus a CDK4/6 inhibitor. One trial called SONIA examined whether this is the right approach, or whether patients should just get the anti-endocrine therapy up front and hold off on starting the CDK4/6 inhibitor medication until a later time. It appears that this delayed approach would reduce symptoms as well as cost of the medication, while not reducing benefit from the treatment. Therefore, it appears it is likely fine for some patients to get just anti-endocrine therapy alone initially. However, we don't know how to identify those patients. Researchers are still figuring out which patients should follow this new treatment plan and which should keep getting the double therapy at the beginning. Some more to come in the future. There was a different trial called PADA-1 that included patients taking anti-endocrine therapy and the CDK4/6 inhibitor, palbociclib, upfront. Those patients were monitored using a blood test, looking for a mutation or a change in the estrogen receptor in the cancer. Patients who had that mutation either remained on the same treatment that they'd been on or switched to the next line of therapy, even though their scans didn't show any progression of their cancer. Overall, this switching strategy looks like a very promising approach for managing patients since it may help patients' cancer respond to treatment for a longer period of time. Although this approach is not yet officially recommended according to our guidelines. In another example, many patients with all types of metastatic breast cancer are treated with a drug called capecitabine, also known as Xeloda. Although this drug is effective for many cancers, many patients experience hand-foot syndrome, nausea, diarrhea, and mouth sores. In the X7-7 clinical trial, the researchers compared the official standard FDA-approved dose based on a patient's height and weight and given for 14 days followed by 7 days off. That was compared to a fixed dose of treatment given 7 days on and 7 days off. The trial found that the fixed-dose regimen was easier to tolerate, but importantly, the benefit from the 2 doses and schedules of treatment appears to be similar. Therefore, we will likely be using this lower dose, 7 days on and 7 days off, for most of our patients who receive treatment with capecitabine for metastatic breast cancer, since it is likely to improve their quality of life while not negatively impacting the potential benefit they receive from the therapy. There were a lot of other research findings presented that are related to treatment for both early-stage and metastatic breast cancer at the meeting. Importantly, we got glimpses of the many new drugs on the horizon for treatment of breast cancer, including a new antibody-drug conjugate against HER2, as well as other new anti-endocrine and targeted treatments. We eagerly await the results of large, randomized trials so the drugs that work can be used to treat patients with breast cancer. But for now, that's it for this quick summary of important research from the 2023 ASCO Annual Meeting. Stay tuned to Cancer.Net for future updates from upcoming breast cancer conferences. Thank you. ASCO: Thank you, Dr. Henry. Next, Dr. Christopher Flowers discusses new research in lymphomas and multiple myeloma. Dr. Flowers is the Chair of the Department of Lymphoma/Myeloma at The University of Texas MD Anderson Cancer Center and Division Head ad interim of Cancer Medicine. He is also the 2023 Cancer.Net Associate Editor for Lymphoma. You can view Dr. Flowers’ disclosures at Cancer.Net. Dr. Flowers: Hello. I'm Dr. Christopher Flowers, professor and chair of the Department of Lymphoma and Myeloma and interim division head for cancer medicine at the University of Texas MD Anderson. And it's my pleasure to talk to you today in this Cancer.Net podcast about latest updates in the hematological malignancies focused on lymphoid cancers from the American Society of Clinical Oncology Annual Meeting. The ASCO Annual Meeting every year is an exciting time for latest updates in the care of patients with cancer. And in particular this year, there were 3 abstracts that I'd like to highlight that were presentations at this meeting about lymphoid malignancies that have potential significant impact for patients over time. The first 2 come from a special session that was on late-breaking abstracts that were latest advances from clinical trials. The first is from the ZUMA-7 trial. This is a trial looking at axicabtagene ciloleucel, a chimeric antigen receptor T-cell therapy, or CAR T-cell therapy. The CAR T-cell trial in question here was led by Jason Westin, who's a colleague of mine at MD Anderson. And MD Anderson is a partner with Kite pharmaceutical company that is a manufacturer of this and has a research alliance with that group. In the ZUMA-7 trial, this was a trial that involved the use of CAR T-cell therapy in comparison to standard-of-care therapy, which typically would be aggressive chemoimmunotherapy followed by autologous stem cell transplantation for patients with relapse of large B-cell lymphoma. As many of you may know, large B-cell lymphoma is a kind of lymphoma that is potentially curable with standard frontline therapy. And when patients relapse, the standard of care historically had been for patients to receive autologous stem cell transplantation, which is also potentially a curative therapy. This trial to do a ZUMA-7 trial compared patients who received the typical standard of care, the autologous stem cell transplant following the aggressive chemoimmunotherapy regimen for patients who had relapsed early after their initial therapy, so within 12 months, or were refractory, meaning that they did not respond to their initial therapy. And this was compared to the axicabtagene ciloleucel or axi-cel CAR T-cell therapy. The initial publication of the trial came out in the New England Journal of Medicine in 2022 and showed that the event-free survival for patients who receive CAR T-cell therapy was superior. This update of the ZUMA-7 trial at the ASCO Annual Meeting that was presented by my colleague, Jason Westin, discussed the overall survival of the study, and in this update, it showed that overall survival was also improved for patients who received axi-cel as opposed to standard-of-care therapy. And now with a median follow-up of a little bit more than 47 months, axi-cel demonstrated superiority that was statistically significant and clinically meaningful over the traditional standard of care. In that same session, there was another trial looking at CAR T-cell therapy for patients with multiple myeloma. This was a BCMA-targeted CAR T-cell therapy that was presented by Dr. Dhakal in that session providing results from the CARTITUDE-4 global randomized phase 3 clinical trial. That was a trial that involved 419 patients where patients were randomized to cilta-cel CAR T-cell therapy for myeloma or standard-of-care therapy, which in this case included combination therapy. And in this trial, this showed that single agent with a single cell-to-cell infusion significantly improved progression-free survival versus standard of care for patients with multiple myeloma who had 1 to 3 prior lines of therapy and were refractory to lenalidomide. This is also a meaningful advance for patients with this disease. And the final abstract that I'll mention is an abstract that was presented by Dr. Alex Herrera from City of Hope and was presented in the Plenary session. And it was really exciting to see a Plenary session presentation focusing on lymphomas. So this trial presented by Dr. Herrera was led by the Southwest Oncology Group. Dr. Sara Ahmed from MD Anderson, from my institution, was a participant and actively engaged in this clinical trial. This trial was a success in a number of ways. First, it involved both pediatric and adult patients and is one of the first trials of its kind to involve both large populations of patients with pediatric lymphomas as well as adults with lymphomas. It helps to consolidate the approaches that we use for Hodgkin lymphoma, both in the pediatric population and the adult population. It also represents a major advance in the ways that we conduct clinical trials in the United States in that this clinical trial finished ahead of schedule in terms of completion of the trial with collaboration from the adult and pediatric groups across the National Clinical Trials Network. As I mentioned, this was presented by Dr. Alex Herrera in the Plenary session and involved patients with stage 3, 4 Hodgkin lymphoma, where patients were randomized 1 to 1 either to receive an anti-PD-1 therapy, nivolumab, with chemotherapy, the AVD chemotherapy regimen, or the antibody-drug conjugate, brentuximab vendotin, combined with that same AVD chemotherapy. And what this showed in 994 patients who were enrolled from 2019 to 2022 was that there was a benefit for patients who received the combination of nivolumab AVD or NAVD versus the group that received brentuximab and AVD. It improved the progression-free survival in patients with advanced-stage Hodgkin lymphoma. In this trial, few immune-related adverse events were observed and a lesser number of patients went on to receive radiation therapy, which is also a benefit for patients with Hodgkin lymphoma. And this concludes my presentation of abstracts at the ASCO Annual Meeting and really exciting advances for patients with lymphoma that were presented this year. ASCO: Thank you, Dr. Flowers. Finally, Dr. Roy Strowd discusses new research in treating brain tumors, including those in people with von Hippel Lindau syndrome. Dr. Strowd is a neurologist and neuro-oncologist at Atrium Health Wake Forest Baptist Comprehensive Cancer Center. He is also the 2023 Cancer.Net Associate Editor for Central Nervous System Tumors. You can view Dr. Strowd’s disclosures at Cancer.Net. Dr. Strowd: Hello, everyone. This is Roy Strowd. I'm a physician neuro-oncologist at Wake Forest University School of Medicine in our comprehensive cancer center. And I’m really excited to be with you for this podcast on important CNS or brain tumor updates from the 2023 ASCO Annual Meeting. I don't have any relevant disclosures for the research that we'll discuss today. It was a really exciting meeting. It was actually a really fun meeting to be a brain tumor doctor at ASCO this year. So I'm really excited to talk with you about some important updates. And I think it's actually a really important time to be a patient and a caregiver and know some of the things going on in brain tumor care. So I'm going to dive into 3 studies. And one that we just have to talk about, and this was a really exciting study called the INDIGO study. At ASCO, if you present a study, you want to have a Plenary presentation, you want to be up on the big stage presenting your work. And brain tumor studies aren't always on the big stage. We just haven't had enough really good treatments out there for brain tumor patients over the years. And this year, we had a Plenary presentation, a really big study, making a big splash. And that was this INDIGO study. So I'm going to spend a few minutes talking about that study. I want brain tumor patients and caregivers to know about this and know about some of the important updates from the Annual Meeting. The study was called the INDIGO study, and it's a phase 3 study. So when you think about clinical trials, there's a phase 1, phase 2, phase 3. That phase 3 is that last step, that last hurdle that a drug needs to overcome to move towards approval. And a positive phase 3 study is really exciting for the field and means that we may have a new treatment that will change how we take care of brain tumor patients. And that's what this study was. It was also a really unique study. So it's looking at a different group of brain tumor patients, patients that have an IDH mutant glioma. Most common brain tumors that we see are the glioblastomas. And those are often and really, by rule, IDH wild-type. IDH is a gene. It's called the isocitrate dehydrogenase gene. And it's one of these really important genes for us to understand how brain tumors are going to work and how they act and it turns out, with this study, how they may respond to treatment. So this study looked at enrolling patients that had an IDH-mutant low-grade glioma, or a grade 2 glioma. Those are those often slower-growing, but they continuously grow tumors that occur early in life, typically in the 30s or 40s for young people. And we haven't really had a lot of good treatments for these patients. And so this study looked at giving a new drug that's called vorasidenib. It's hard to say vorasidenib. And it's an IDH mutant inhibitor. So it attacks that IDH mutant gene that makes these tumors what they are. And it's been undergoing development for many years. It's an exciting treatment because it's what we call a molecularly targeted treatment. It specifically targets that IDH gene that makes the low-grade tumors low-grade tumors. This study enrolled 331 patients, so a large group of patients. Half of those patients received the drug, the vorasidenib, and half received placebo. And that's pretty uncommon in cancer. We don't often do studies that are placebo-controlled studies. But for these patients, there's often not a good treatment early in the course, they get surgery. And for patients that don't need an additional treatment, we do surgery and then we wait and watch and see what happens. And that gives us an opportunity as a brain tumor community to figure out whether this type of treatment will help prevent the need for a next treatment, prevent the need for radiation and chemotherapy. And so that's what was looked at in this study. And there was some really exciting data. So I'm going to go through a few numbers, but we just got to talk about these numbers because they're really important. So at 14 months, 28% of the patients receiving the drug vorasidenib had progressions. That's about a quarter of patients compared to half that received placebo. So that's a big improvement in the number of patients whose tumor grew. So this drug prevented tumor growth in these patients. And that's exactly what we want. That's why we develop drugs, is to prevent tumor growth. When we look at the time that those patients had until they needed a next treatment or until their tumor grew, it was over 2 years of time patients receiving the drug when their tumor grew versus less than a year, 11 months for those receiving placebo. So it's adding a lot of time for brain tumor patients without tumor growth or without needing another treatment. And typically, these patients with low-grade gliomas would need something like radiation therapy or chemotherapy. And those are good treatments, and we need those treatments. But they can have toxicity. And so this is the type of drug that could prevent that toxicity, cognitive decline, other problems that can happen with chemotherapy that those patients didn't potentially suffer. So there are some important things that we learned from the INDIGO study that I would want you to take away, kind of what do these data mean? The first is that we can target this IDH gene. And that's really important for our field. And it means if you're a brain tumor patient, knowing whether your tumor is IDH mutant or IDH wild-type is important, and that's something I want brain tumor patients to ask me as a neuro-oncologist and ask their cancer doctor because that's important in deciding treatment for them. The second is this medicine vorasidenib, it gets into the brain. And that's one of the big challenges that we have in brain tumor care in developing drugs is we need things that get into the brain. And this study really shows that this is a good medicine. There's a number of IDH inhibitors, but this medicine vorasidenib is one that we want to specifically think about for our patients. And this is a practice-changing study. So for the first time, we now have a treatment that works for grade 2 gliomas and really prevents the need for radiation therapy and chemotherapy. So those are 3 important things to take away from this. There's a number of things that we don't yet know. This medicine is not available. So patients coming in and emailing me and calling me, we don't have it yet. And after a big phase 3 study like this, this is announced. There's still a number of steps that need to happen to make sure that this can be delivered to patients safely and we can get it out there. And that's in partnership with groups like the FDA, the Food and Drug Administration, and others. So this is an important conversation to have with patients, neuro-oncologists, and to know that this is something that's on the horizon. Two other things is we don't know if this is going to work for all brain tumors. In particular, for these IDH wild-type glioblastomas, the most common brain tumor, this probably is not a good therapy that we don't have any data to suggest that it would work. They don't have that IDH mutation. And so this is important for some brain tumor patients but not for everybody. And that needs to prompt a conversation with the cancer doctor. And it may not work at all times. So there's some data to suggest that this is really a drug that's best given early in the course of treatment and not later on. And so it is something that I want my patients to be aware of at the first time that I see them so we can be deciding what kind of the right time is. So I want to give folks 2 take-homes from this study and summarize a few of these things that we heard about because it's such an important study. So what are the 2 take-homes from the INDIGO Study? The first that I wrote down is targeting IDH mutation in glioma works. And that's a groundbreaking discovery from this. This is really important for our field. IDH mutations have been important to diagnose brain tumors but have never been really a therapeutic target. And this changes the landscape, and we can now target IDH mutations in gliomas. And that's really important. The second thing, the second real take-home message, is we can safely delay radiation therapy and chemotherapy in some patients with these lower-grade gliomas, potentially with IDH mutation and IDH inhibition. And that's really important. Chemotherapy and radiation therapy are important, but if we can delay those treatments and prevent side effects, that could be helpful for some of our patients. So really important update from ASCO and what I want to spend most of the time on our podcast focusing on this INDIGO study. But there were a bunch of other things going on in brain tumors at ASCO, as there always are. And I want to highlight 2 studies about some things that the groups of patients may be interested in knowing that happened at the meeting. The first is a study called the INB-200 study. And this is a phase 1 study, so it's earlier in development. But it's an immunotherapy study. And brain tumor patients and caregivers will know that we've really wanted to find an immunotherapy that works for brain tumors. And we haven't yet. And we're still not there, but this study is an important step in that direction. So this study from a group at the University of Alabama looked at something called gamma delta T cells. And T cells are really important. They're part of the anti-tumor response. They're what the body uses to attack the tumor. So we like those T cells. And particularly, these gamma delta T cells are important in targeting tumor cells in glioblastoma cells. They're also unique. They can avoid the toxicity of chemotherapy. Radiation therapy and chemotherapy suppresses the T cells. They make some go down, or decreased in number, which is not what we want. And these gamma delta T cells were genetically created so that they were resistant to chemotherapy. And that's really, really important. We want an immunotherapy that works and one that isn't suppressed by our other treatments. And that's been a real barrier for glioma patients. So in this phase 1 study, they found the right dose of these gamma delta T cells, and that's the goal of a phase 1 study. But there were some early signs that this may be changing the tumor. One of the patients underwent surgery before and after they got this infusion. And we were able to see this. Investigators were able to see the gamma delta T cells up in the tumor. So this doesn't change practice. Patients don't need to go out and seek out the gamma delta T cells yet. But it's one of those early findings that says that we need to keep looking at immunotherapy. And as a community, this is something we need to keep focusing on. And then the last abstract and study I wanted to focus on is for a rare disease. This would not be something that would be relevant for all of our listeners and the brain tumor patients but for a subgroup of patients that have a condition called VHL, or von Hippel-Lindau. And von Hippel-Lindau is a genetic condition. So, most brain tumors are not inherited. You don't get it from a mom or a dad or pass it on, except for these patients, you do. And it comes from a gene that's inherited in families called the VHL or the von Hippel-Lindau gene. And these patients are predisposed to get tumors all throughout the body and the kidneys and the brain and the eye. And this is a lifelong disease where these tumors can really grow slowly over time and cause significant problems. And in the past few years, there's been a new treatment called belzutifan. Belzutifan is the name of this drug that has been shown to be effective in the kidney tumors for patients with VHL. And at ASCO this year, there was a new study showing that it's also effective in treating the brain tumors for these patients. And that's really important. We just haven't had a treatment other than surgery or radiation therapy for these tumors. And oftentimes, they grow after surgery and radiation therapy and we need an additional treatment. So in this study, the investigators looked at, "Does this drug belzutifan work for treating the CNS tumors, hemangioblastoma?" And found that around 50% of patients had a response, so a shrinkage in the size of the tumor. 90% of patients had control of their brain tumor disease, which is really important. And it worked really quickly, so it worked in about 3 to 5 months, which is shorter than what we would see for the kidney tumors. So that's exciting news for VHL patients, patients with von Hippel-Lindau, and another important update from the 2023 ASCO. So thanks for listening to this update of CNS brain tumors at the 2023 ASCO Annual Meeting. Again, I'm Roy Strowd, a neuro-oncologist at Wake Forest University School of Medicine. Delighted to bring you this brief summary of new research in the field. ASCO: Thank you, Dr. Strowd. You can find more research from recent scientific meetings at www.cancer.net. Cancer.Net Podcasts feature trusted, timely, and compassionate information for people with cancer, survivors, and their families and loved ones. Subscribe wherever you listen to podcasts for expert information and tips on coping with cancer, recaps of the latest research advances, and thoughtful discussions on cancer care. And check out other ASCO Podcasts to hear the latest interviews and insights from thought leaders, innovators, experts, and pioneers in oncology. Cancer.Net is supported by Conquer Cancer, the ASCO Foundation, which funds lifesaving research for every type of cancer, helping people with cancer everywhere. To help fund Cancer.Net and programs like it, donate at CONQUER.ORG/Donate.