2018 ASCO Annual Meeting Research Round Up: Childhood Cancers, Older Adults, Multiple Myeloma, and Lung Cancer
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The ASCO Annual Meeting brings together physicians, researchers, patient advocates, and other health care professionals to discuss the latest in cancer care. The research presented at this meeting frequently leads to treatment advances and new ways to improve the quality of life for people with cancer. In today’s podcast, Cancer.Net Associate Editors share their thoughts on the most exciting and practice-changing news to come out of the 2018 ASCO Annual Meeting.
First, Dr. Daniel Mulrooney will discuss a large international study on maintenance chemotherapy for rhabdomyosarcoma, and several studies on the benefits of physical activity for survivors of childhood cancer. Dr. Mulrooney is an Associate Faculty Member in the Division of Cancer Survivorship at St. Jude Children’s Research Hospital. He is also the Cancer.Net Associate Editor for Childhood Cancers.
Dr. Mulrooney: This is Dr. Dan Mulrooney from St. Jude Children's Research Hospital. I'm the Deputy Director of the After Completion of Therapy Clinic at St. Jude and primarily care for survivors of pediatric solid tumors. During this year's Annual Meeting of the American Society of Clinical Oncology, a very interesting, large, international study investigating maintenance treatment for rhabdomyosarcoma was highlighted during the plenary session. Maintenance chemotherapy, or prolonged low-dose chemotherapy, is used most frequently in the treatment of acute lymphoblastic leukemia, or ALL, but less so for pediatric solid tumors.
In a study conducted by the European Paediatric Soft Tissue Sarcoma Study Group that included patients from 14 different countries, investigators studied adding maintenance chemotherapy to the treatment of high-risk rhabdomyosarcoma. Rhabdomyosarcoma is a rare tumor, which mostly occurs in children but can also present in adults. Fortunately, treatment is often successful. But up to 20 to 30 percent of patients may still relapse after treatment meaning additional treatment is needed and making long-term cure more difficult. Standard treatment involves 6 to 8 months of intensive chemotherapy, radiation, and surgery. These investigators wanted to know if adding additional low-dose chemotherapy for six months after standard treatment might improve survival. They studied patients greater than 6 months to less than 21 years of age with high-risk disease based on the histology and location of their tumors. 186 patients were randomized to standard therapy. And 185 were randomized to receive the additional 6 months of maintenance chemotherapy, which included vinorelbine given IV, weekly, for 3 weeks every month, and cyclophosphamide taken orally everyday. And at 5 years, the overall survival was statistically better in the maintenance chemotherapy group, 87% versus 74% in the standard therapy group. Fortunately, toxicity from the additional chemotherapy was minimal and mostly included low blood counts, although approximately 30% of patients also had an infectious complication. These investigators concluded that this additional maintenance therapy is an effective and well-tolerated strategy for patients with high-risk rhabdomyosarcoma and proposed to investigate this method in other solid tumor types.
Now additionally, a number of studies presented at the meeting highlighted the importance of physical fitness among childhood cancer survivors. A study from the University of New South Wales in Sydney, Australia collected physical activity data from the parents of childhood cancer survivors and a control population. Fortunately, the parents of survivors reported more physical activity in their children than the control parents with 31% of survivors meeting the recommendations of the American Cancer Society for moderate to vigorous physical activity, which is greater than or equal to 300 minutes of activity per week. However, nearly two-thirds of survivors did not meet the recommended activity level.
Subsequently, a large study from the St. Jude Lifetime Cohort assessed 577 childhood cancer survivors, and 286 healthy community controls. In this study, individuals underwent a series of tests including an echocardiogram and cardiopulmonary exercise testing on a treadmill. Measures of relative peak oxygen uptake or “VO2 max” were obtained to assess exercise capacity. Survivors had a lower VO2 max compared to controls, and this worsened with increasing intensity of previous exposure to cardiotoxic therapies such as anthracyclines and chest radiation. This was also associated with a relatively new measure on echocardiography called global longitudinal strain. In fact, global longitudinal strain, and not the more common measure of ejection fraction, was associated with impaired VO2 max among cancer survivors. Global longitudinal strain may become an important new screening marker for cancer survivors.
And finally, 2 studies from the Childhood Cancer Survivor Study, or CCSS, highlighted the importance of exercise for childhood cancer survivors. The CCSS is a multi-institutional study that uses questionnaires to assess outcomes among a large population of cancer survivors from across North America. Investigators collected data on physical activity, classified as metabolic equivalent tasks, or METs, and expressed as MET-hours per week. Exercise levels were categorized into groups ranging from none or 0 MET-hours per week and increasing incrementally to 3 to 6, 9 to 12, and 15 to 21 MET-hours per week. 3 to 6 MET-hours per week is equivalent to approximately 20 minutes of brisk walking per week, and 15 to 21 MET-hours per week is equivalent to approximately 60 minutes of brisk walking every day for 5 days per week.
And in the first study, investigators showed a decrease in psychological burden among cancer survivors, decreased depression and somatization, and improvements in quality of life and cognitive function among those with increased levels of physical activity. As little as 20 minutes of brisk walking per week was associated with this lower psychological burden. Importantly, in a longitudinal analysis, CCSS investigators showed a decrease in mortality with increasing intensity of physical activity. And looking over eight years, survivors who increased their level of exercise had a 40% reduction in the rate of death compared to those who maintained a low level of exercise. Taken together, these studies presented at the 2018 ASCO Annual Meeting highlight the safety and significant health and psychological benefits of exercise for survivors of childhood cancer.
ASCO: Thank you Dr. Mulrooney.
Next, Dr. Hyman Muss will discuss a study on a tool that can be used to improve communication between older adults with cancer and their doctors. Dr. Muss is a Professor of Medicine at the University Of North Carolina School Of Medicine, and the Director of the Geriatric Oncology Program at the University of North Carolina Lineberger Comprehensive Cancer Center Program. He is also the Cancer.Net Associate Editor for Geriatric Oncology.
Dr. Muss: My name is Hy Muss, and I'm a medical oncologist with a major interest in geriatric oncology. And today I'm going to talk about what I think is 1 of the most exciting studies I've seen in years pertaining to cancer care in older patients, an ASCO presentation by Dr. Supriya Mohile and our colleagues on a large, randomized trial they did, focused on improving communication of older patients with their physician.
So this was a very large PCORI-funded trial in the United States, a federally funded study for patients 70 and older with a whole variety of different cancers. And in this study, what happened were older patients were either randomized to an intervention, which included giving a questionnaire, a geriatric assessment, that asked about function and all types of other issues related to older people, social support etc. And together with that information, there were recommendations for the doctor to talk with the patient about, such as if they had poor social support, maybe get them to a senior facility. Or if they had problems getting meals, set up meals on wheels. Or if they had a physical handicap, get them to physical therapy to try to overcome it. So that was all provided to the doctor.
And the second group of patients just got kind of very little information sent to the doctor. And so what happened in this trial, which was extremely exciting, was that they had 500 patients accrued to this, so this is a huge number of patients. And about half were given the intervention arm and half were just routine care. And it showed that the patients who went through the intervention, and that information was provided to the doctor, had much better communications with the doctor about their illnesses, about their cancer care.
And more importantly, it led to interventions that were very helpful and that probably improved their quality of life and physical well-being, although, these data were not reported in the presentation. And this is really special, because the standard care arm, a lot of things were not discussed, and a lot of things that older patients had may not be related to their cancer but are extremely important for the oncologist to know. And these are things like, "How are you doing at home? Are you able to care for yourself? Do you pay your bills? Do you have good social support? Can you go to the grocery store, etc.? Also, what are your friends like? What are your family like? Do you have people interested in you that take you out, do things?" And frequently, those issues aren't discussed, and they're integral to the care of older people.
So they showed the value of a geriatric assessment, which discovers many more things than the usual questions doctors ask you in 1 or 2 sentences about your function. And more importantly, they improved care, they improved communication, and they led to interventions that make people's lives better, and perhaps, someday a lot longer.
So I thought this was a terrific study. Dr. Mohile and her colleagues broke the glass on showing how important geriatric assessment—where we ask questions about your function, about your health and other things, that are generally not part of a routine history and physical—how important this is to improving care. So I hope you take a look at this at the ASCO site. It's a wonderful trial, and I think it's the beginning of many more similar trials to come. Thank you.
ASCO: Thank you Dr. Muss.
Next, Dr. Michael Thompson will discuss several topics in multiple myeloma that were explored at the 2018 ASCO Annual Meeting, including a discussion on the cost and value of myeloma drugs, a study that compared different doses of a treatment for relapsed refractory multiple myeloma, and several studies that explored ways to personalize myeloma treatment, also known as precision medicine. Dr. Thompson is a hematologist/oncologist, and the Medical Director for the Early-Phase Cancer Research Program and the Oncology Precision Medicine Program at Aurora Health Care in Wisconsin. He is also the Cancer.Net Associate Editor for Multiple Myeloma.
Dr. Thompson: Hello. I'm Mike Thompson, a hematologist/oncologist at Aurora Health Care of Wisconsin. I'm also the Associate Editor for Cancer.Net on myeloma. Today, I'm going to discuss a few myeloma-related areas reported at the ASCO 2018 Annual Meeting. The first is a value debate, which was on Sunday, between Mayo colleagues and friends, Dr. Fonseca and Dr. Rajkumar, who had discussed the question of costs and value in multiple myeloma in this session, Global Myeloma, Health Disparities, and the Cost of Drugs. They disagreed on some issues. But my take-home from their debate was that both the absolute costs of care as well as value, which was utility divided by cost, are important to our entire healthcare system as well as to patients and their families. There was no immediate changes to costs of care after that debate, but I think it's something important that we will all be watching as new drugs are developed in the future.
Another important study was the A.R.R.O.W. study, which was reported on by Dr. Mateos, and was later published with the first author, Dr. Moreau. This was a phase III study of 2 different doses of carfilzomib with dexamethasone in relapsed and refractory myeloma patients. So there was the traditional twice-weekly dose, and there was the once-weekly dose. And the conclusions were that the once-weekly dose with a dose up to 70 milligrams per meter squared improved progression-free survival and overall response rate. And later in the publication, it showed that it improved survival versus the twice-weekly dose at 27 milligrams per meter squared, with a similar side effect profile.
So that is very good news for patients that might get that doublet therapy and have to come into the office less frequently. The caveats with that study are that this dosing was not compared to an intermediate dose of 56 milligrams per meter squared, which has been widely used after that study was published a few years ago. So it's looking at the lowest dose versus the highest dose. And it's also for patients with a performance status of 0 to 1, which means they're doing well. And for many of those patients, we wouldn't use a doublet therapy; we'd use a triplet therapy. So that may limit the applicability in practice, at least, in the United States. And we also don't know that combining this Kd regimen with another myeloma drug is safe or effective, so those studies are ongoing.
And the third topic that was of interest at ASCO 2018 was precision medicine in multiple myeloma. So there were at least 3 parts to this. One is risk stratification. And this has been going on for a while, looking at the cytogenetics and FISH. And the NCCN and Mayo mSMART guidelines give some guidance on how to treat based on risk. Also there was talk about the CAR-T therapies, which may be the most specific or precision type of medicine you can get. And those studies are ongoing but not yet widely available for myeloma, but everyone is very interested in those data. Other therapies were targeted therapies, and there are not as many examples in multiple myeloma as there are in some diseases like lung cancer. But there are some alterations such as BRAF, where BRAF inhibitors are used or can be used in a few patients, in myeloma that have that. And there's great excitement about the BCL-2 inhibitor or venetoclax for t(11;14), which is the most common translocation found in multiple myeloma.
So those are some of the main things I took away from this ASCO meeting. We really need to think about costs and value and the impact it has on our patients. We need to think about trying to dose drugs in ways that are more convenient to patients, and in this case, seemed to be more beneficial. And we have to keep looking ahead to do more things with targeted therapies to see if we can get away from some of the toxicities of some of our chemotherapy agents. Coming up will be more studies over the next year for ASCO 2019, and I look forward to seeing what changes between now and then.
ASCO: Thank you Dr. Thompson.
Finally, Dr. Jyoti Patel will discuss the ongoing research in targeted therapy and precision medicine for lung cancer. Dr. Patel is Professor of Medicine and Director of Thoracic Oncology at the University of Chicago and is the Cancer.Net Associate Editor for lung cancer.
Dr. Patel: Hello. I'm Jyoti Patel. I'm the Director of Thoracic Oncology at the University of Chicago and a long-time ASCO member, and I would like to talk to you today about some of the most important research takeaways from our recent ASCO Annual Meeting. So remember, this is a meeting where about 40,000 cancer care providers come together to discuss and to present the most groundbreaking research and its impact for patients. So this is certainly a meeting that is exciting for all of us and really represents, I think, the best of what's happening in the field.
I think when we look at what's happening with lung cancer—because there's so many people affected with lung cancer in the United States where nearly 200,000 people every year are diagnosed with lung cancer—we can say that we've made significant leaps forward in the past decade, and it's really changed the paradigm in how we treat patients with advanced disease. So it's a disease in which systemic therapy is really the mainstay of therapy because it's not confined to the lung where we may do surgery or radiation, this is really a disease that has spread and is treated as a more chronic condition.
Our efforts at understanding the biology of cancer have really now come back to the bedside, and many of the groundbreaking research trials that were presented really revolved around this idea of personalization of therapy based on biomarkers. Understanding the cancer genome now has a direct impact for our patients. When patients are diagnosed with advanced disease, I think all of these studies point to the fact that we need to have adequate characterization of the tumor. So it's no longer okay to say my patient has non-small cell lung cancer, which is the most common kind of lung cancer, it's really incumbent upon the oncologist, and pathologist, and pulmonologist, and surgeon to come together and further define whether or not there are particular mutations that would serve as good targets for drugs, or whether this is an inflamed tumor and may be best treated with immunotherapy.
When someone's diagnosed with lung cancer, I know it's often difficult for a patient, or family member, to first meet the oncologist and say yes, we have this diagnosis, but I'm waiting for additional tests. But that time that it takes to do this testing—and it's very complex, we look at anywhere from 3, at the very minimum, to almost 1,000 genes at my institution's program—in which we try to match particular drugs with therapies. And the reason we do this is because in about 30 or 40 percent of patients with non-small cell lung cancer that's non-squamous, the most common kind, we're able to find an easily druggable target. So we find EGFR and ALK and ROS1, and so we've got updates on all of those targets at ASCO.
But this year there was really a lot of excitement about a new target called the RET fusion protein and when 2 chromosomes sort of flip-flop and form a protein that causes this cancer to grow. Now this is uncommon, and medically it affects about 1 to 2 percent of patients with lung cancer, but when you look at the enormous burden of lung cancer, that's thousands of patients a year.
What we found was that there's a really selective drug that targets this protein and can shut down the cancer cells and cause deep responses, so almost 80 percent of patients with significant reduction in their tumor and lung responses with an oral tablet that's very well-tolerated. The idea is that we need to absolutely try to do a biopsy, understand if there are multiple markers, and that list continues to grow for which there are druggable targets. And there was a lot of excitement about drugs that target genes such as the MET exon 14 oncogene, or something that's been very elusive for some time, the EGFR exon 20 mutations. These are single sort of base misreads in our DNA that causes cancer to grow, but if 1 patient has this target, and we're able to deliver a drug that causes patients to have nice responses and a return to wellness, I think that's great for all of us.
Often getting the right tissue is tough because sometimes we just don't have enough tissue. And, certainly, we've seen considerable progress with liquid biopsies in recent years, and there's been good concordance between blood-based biopsies as well as tissue, and so our field is rapidly evolving in ways that we can bring the best drugs to the best patients.
We're starting to do this with immunotherapy. There's a protein called PD-L1 which helps us assign appropriate therapy for patients. And so if someone has a high PD-L marker on their tumor, those patients may get immunotherapy alone with an expectation that they would have a nice response and durable disease control with good quality-of-life. So with effort to really characterize tumors, although it can be difficult when someone's first diagnosed to wait to get all these markers right, which is on the order of about 2 to 3 weeks, the downstream effects of characterizing the tissue and getting the right drugs to the right patients are really enormous because we are able to see patients that return to wellness.
Certainly this was an exciting meeting. And I think more and more we're seeing not only medical oncologists, but patients and patient advocates, understanding the importance of biopsies, and an incredible effort by industry, as well, to really make these assays and these tests more accessible to patients, and to make the turnaround times even faster, and to use less tissue to get the right answers. I'm optimistic that we'll continue to see this trend, and there will be more and more drugs that will be optimized for particular patients.
ASCO: Thank you Dr. Patel. If this podcast was useful, please take a minute to subscribe, rate, and review the show on Apple Podcasts or Google Play.
To learn more about all of the science presented at the 2018 ASCO Annual Meeting, visit www.cancer.net/ascoannualmeeting. If you have questions about whether new research may affect your care, be sure to talk with your doctor.
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