Jul 21, 2020
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Every year, the ASCO Annual Meeting brings together attendeesfrom around the globe to learn about the latest research in thetreatment and care of people with cancer. This year, attendees from138 countries worldwide gathered virtually for the ASCO20 VirtualScientific Program, held Friday, May 29 through Sunday, May 31.
In the annual Research Round Up podcast series, Cancer.NetAssociate Editors answer the question, “What was the mostexciting or practice-changing research in your field presented atthe ASCO20 Virtual Scientific Program?” In this episode, 3editors discuss new research in the fields of breast cancer,sarcoma, and palliative and supportive care.
First, Dr. Norah Lynn Henry will discuss 3 studies thatexploring treatment options for different types of breast cancer.Dr. Henry is an Associate Professor in the University of Michigan'sDivision of Hematology/Oncology in the Department of InternalMedicine and is the Breast Oncology Disease Lead at the RogelCancer Center. She is also the Cancer.Net Associate Editor forBreast Cancer.
View Dr. Henry’s disclosures at Cancer.Net.
Dr. Henry: I'm Dr. Lynn Henry, one of thebreast cancer experts from the Rogel Cancer Center at theUniversity of Michigan. I would like to share with you a few of theresearch highlights related to breast cancer from the ASCO 2020Virtual Scientific Program. I do not have any relationships todisclose related to any of these studies. There were many excitingtrials presented at this conference for all types of breast cancer.Today I will highlight 3 key studies that will likely change how wetreat patients with breast cancer. Before I start talking about thetrials themselves, I'm going to give a very brief overview of thetypes of breast cancer. Then I will talk about an important studythat looked at the use of surgery and radiation in patients whosecancer is metastatic or has already spread to other sites of thebody at the time they are diagnosed with breast cancer. Then I willhighlight some research that was presented on triple negative andHER2-positive metastatic breast cancer.
As a brief review, there are multiple kinds of breast cancer.Some breast cancers are called hormone receptor positive orestrogen receptor positive and are stimulated to grow by estrogen.We treat those cancers with anti-estrogen treatments to blockestrogen or to lower estrogen levels. Other breast cancers arecalled HER2-positive. These are often more aggressive cancers, butbecause they have extra copies of the HER2 receptor, they oftenrespond to treatments that block HER2. Finally, there are breastcancers that don't have any hormone receptors or HER2 receptors.These are called triple-negative breast cancer and are also oftenvery aggressive cancers.
The first clinical trial I'm going to discuss was a relativelylarge trial conducted by the ECOG-ACRIN cooperative group. Ofpatients newly diagnosed with breast cancer, about 6% are actuallyfound to have cancer in other sites in their body such as in thebone, liver, or lung, as well as in the breast. This is called denovo metastatic breast cancer. The goal of this trial was todetermine whether patients in this situation should have surgeryand radiation to treat the cancer in their breast in addition todrug treatment, or whether they should just have drug treatment fortheir cancer. In this trial, patients with de novo metastaticbreast cancer of any type were treated with appropriate drugtherapy for 4 to 8 months. The approximately 250 patients whosecancers improved with treatment were randomized to either havebreast surgery and, if appropriate, radiation therapy, and thenresume drug therapy or to just continue drug therapy the entiretime. Overall, there was no difference in how long patientssurvived whether they had removal of the breast mass or not. Inaddition, the quality of life in the 2 groups of patients alsoappeared to be similar. These results confirm studies that havebeen conducted in other countries around the world and importantlyexamined whether surgery is appropriate in patients who are treatedwith modern therapies. It appears that surgery is not needed inmost patients. This is important information for patients with denovo metastatic breast cancer who are trying to decide whether ornot to have breast surgery as part of their treatment.
The next trial is called KEYNOTE-355 and examined the use of animmunotherapy drug pembrolizumab, also called Keytruda, in patientswith triple-negative metastatic breast cancer. Immunotherapy is atreatment type that allows a patient's own immune system to helptreat her cancer. We already have the FDA approved option of usinga similar immunotherapy medication called atezolizumab, also calledTecentriq, in combination with a specific chemotherapy drug forpatients whose cancer express PDL1. In this new KEYNOTE trial,pembrolizumab was combined with 1 of 3 possible chemotherapyoptions in patients with previously untreated metastatictriple-negative breast cancer. In this trial, in patients whosetumors had an increased amount of PDL1 on the cells and in thesurrounding tissue, the addition of pembrolizumab to chemotherapymade it less likely for the cancer to progress compared tochemotherapy alone. Although this treatment combination is not yetFDA approved, all the drugs that were tested are already approvedfor use in other situations. These results are exciting becausethey will likely lead to new treatment options for patients withthis type of breast cancer which can be quite challenging totreat.
Finally, I will highlight new results from the clinical trialcalled HER2CLIMB. This is a large phase 3 trial examining a newdrug called tucatinib that is a pill that is designed to turn offthe HER2 receptor. Patients who enrolled on this trial hadpreviously been treated with multiple different treatments forHER2-positive metastatic breast cancer. All enrolled patients weretreated with the anti-HER2 antibody drug trastuzumab, also calledHerceptin, as well as a chemotherapy drug called capecitabine orXeloda. In addition, two-thirds received the new drug tucatinib andone-third receive placebo. We learned about 6 months ago that thisdrug combination was pretty well tolerated by patients. And what isexciting about this trial is the patients who were treated withtucatinib had a longer time until their cancer progressed and livedlonger compared to those who took placebo. As a result of thistrial, the drug was approved by the U.S. Food and DrugAdministration in spring 2020.
Because of the type of drug that it is, tucatinib is thought totreat cancer both outside and inside of the brain. This isimportant because many patients with HER2-positive breast cancerhave the cancer spread to their brain. In fact, almost half of thepatients enrolled in the trial had a history of metastases in thebrain and many had active growing cancer in their brain at the timeof trial enrollment. Importantly those patients with cancer intheir brain obtained a similar benefit from the drug compared tothose who didn't. Over half of patients with active cancer in theirbrain had at least a partial shrinkage of the cancer in their brainas seen on brain MRI when treated with tucatinib in addition to theother drugs, which demonstrates that tucatinib can get into thebrain to treat the cancer. On average, patients with active cancerin their brain were more likely to live an average of 8 monthslonger as a result of taking tucatinib. This represents an excitingnew treatment option for patients with HER2-positive breast cancerwhose cancer has spread to their brain, and importantly thistreatment is already available for patients.
Overall, there's a lot of exciting research going on across allthe different subsets of breast cancer. As you can see, the resultsof these and many other important clinical trials were reported atthe recent ASCO Annual Meeting and there are many more clinicaltrials ongoing that will hopefully result in the approval ofmultiple new effective treatments for breast cancer. In addition,there's research going on that is examining the impact of treatmenton patients with breast cancer and trying to improve the lives ofthose living with breast cancer. Clinical trials are critical tothe development of these new treatments.
Well, that's it for this quick summary of this importantresearch from the ASCO 2020 Virtual Scientific Meeting. Overall, wecontinue on a fast track in breast cancer with many new andexciting therapies being actively studied and research helpingsupport our patients do better than ever before. Stay tuned toCancer.Net for future updates from upcoming cancer conferences.Thank you very much.
ASCO:Thank you, Dr. Henry.
Next, Dr. Vicki Keedy will discuss an international study thatcompared different treatment options for Ewing sarcoma, as well asnew research in using immunotherapy to treat sarcomas. Dr. Keedy isan Assistant Professor of Medicine in the Division ofHematology/Oncology and the Clinical Director of the SarcomaProgram at the Vanderbilt-Ingram Cancer Center at VanderbiltUniversity Medical Center. She is also the Cancer.Net AssociateEditor for Sarcoma.
View Dr. Keedy’s disclosures at Cancer.Net.
Dr. Keedy: Hello, my name is Vicki Keedy, and Iam the clinical director for Sarcoma at the Vanderbilt-IngramCancer Center at Vanderbilt University Medical Center. I am pleasedto discuss with you some of the exciting research findings in themanagement of patients with sarcomas presented at this year's ASCOAnnual Meeting. I have no direct conflict of interest, but myinstitution does participate in some of the trials using some ofthe immunotherapy agents discussed below. Sarcomas are a class ofcancers made of many different types of connective tissue tumors.Thus, there is significant variety in the types of abstractspresented, making narrowing them down a difficult task. First, Iwill discuss a study that establishes the standard first-linetreatment for patients with Ewing sarcoma. And then, I will finishby summarizing a few abstracts on the use of immunotherapy invarious sarcomas.
Ewing sarcoma is a type of sarcoma that can start in either thebones or soft tissue, tends to occur in children and youngeradults, but can present at any age. It is characterized by small,round blue cells and is considered sensitive to chemotherapy.Regimens using multiple chemotherapy agents are considered thestandard first-line treatment. However, there's variation in theexact regimen with considerable differences between the treatmentsmost commonly used in the United States versus that used in manyEuropean sarcoma centers. EURO EWING 2012, presented by Dr.Bernadette Brennan compared these 2 most common regimens todetermine whether 1 is better in regards to improving survival butalso to evaluate differences in toxicity. In this trial, 640patients in 10 different European countries with newly-diagnosedlocalized or metastatic Ewing sarcoma were randomized to receiveeither the regimen called VIDE, most commonly used in Europe, orthe regimen called interval-compressed VDC/IE, most commonly usedin the United States.
VIDE consists of four drugs - vincristine, ifosfamide,doxorubicin, and etoposide - given together every 3 weeks prior tosurgery. This is then followed by additional chemotherapy of asimilar regimen post-surgery. VDC/IE consists of 2 differentregimens alternating an every 2-week cycle. These are vincristine,doxorubicin, and cyclophosphamide alternating with ifosfamide andetoposide, and these are received both before and after surgery.The results of this study showed an improved survival for patientswho received VDC/IE that was both clinically and statisticallysignificant. Its benefits seem to hold true for patients with bothlocalized and metastatic disease regardless of age. Additionally,VDC/IE appeared to be less toxic with fewer episodes of neutropenicfever and fewer severe treatment-related toxic events, while alsoallowing patients to complete their treatment approximately 3months earlier than patients receiving the VIDE regimen. This studydemonstrates the importance of cytotoxic chemotherapy for patientswith Ewing sarcoma and establishes interval-compressed VDC/IE asthe standard of care.
Moving on to the next topic of immunotherapy and sarcoma, manyof the abstracts presented this year related to use of thoseconcepts in patients with various types of sarcoma. Due to thebiology of sarcoma, the immune system is generally not able torecognize and attack sarcoma cells. Thus, this approach by itselfhas not shown much benefit in most sarcomas. However, as Imentioned, there are many types of sarcomas, and they do not allbehave the same. We have seen signals of benefits in certainsubtypes. Many of the abstracts presented this year evaluatedimmunotherapy in some of these specific subtypes or attempted touse it in combination with other treatments such as chemotherapy orradiation. Unfortunately, these studies were relatively small ordid not compare the immunotherapy to a standard treatment, makingit very difficult to make definitive statements about the results.But they do give us more insights into which types of sarcomasmight benefit from this approach. These abstracts confirmedresponses in undifferentiated pleomorphic sarcoma, synovialsarcoma, alveolar soft part sarcoma, in angiosarcoma, and Kaposi'ssarcoma. There's still much work to be done to determine whether animmunotherapy approach is better than already approved treatmentsfor these types of sarcomas, and it is essential to validate theseresults by treating patients with immunotherapy agents in thecontext of the clinical trial. I thank you for your time and hopeyou found this discussion helpful. I look forward to discussingmore exciting results next year.
ASCO:Thank you, Dr. Keedy.
Next, Dr. Kavitha Ramchandran will discuss several aspects ofresearch in supportive and palliative care that was presented atASCO20. This type of care focuses on managing the symptoms and sideeffects of cancer and its treatment. It also includes support tohelp reduce the financial, emotional, and social effects ofcancer.
Dr. Ramchandran is the Clinical Associate Professor of Medicinein the Division of Oncology at Stanford University, and the MedicalDirector of Palliative Medicine at the Stanford Cancer Institute.She is also the Cancer.Net Associate Editor for PalliativeCare.
View Dr. Ramchandran’s disclosures at Cancer.Net.
Dr. Ramchandran: Hi. It's wonderful to be herewith you all today. My name is Kavitha Ramchandran, and I'm aclinical associate professor at Stanford University in oncology andpalliative medicine and also have the pleasure of being theAssociate Editor for Palliative Care on ASCO's patient educationwebsite, Cancer.Net. And I do not have any conflicts of interest todisclose related to the research that we'll be discussingtoday.
ASCO 2020 was a wonderful year in terms of palliative careeducation and research, and I am excited to share some of thehighlights from that meeting with you all. We'll be talking about afew key research studies, and we'll be discussing a couple ofdifferent things. One, what are some of the novel approaches tosymptom management in palliative care? Two, how do we actuallyassess risk in terms of our patients and how can we better stratifypatients in terms of what type of treatments are best for them, andare there novel tools we can use? Three, how can we improve care byintegrating palliative care early and often, both through a primarypalliative care approach as well as a specialist palliative careapproach? With that, let's go ahead and get started.
So in terms of symptoms, we had a really great discussion by Dr.Roeland from Mass General on several abstracts. The couple ofabstracts that we're going to focus on here, one looked atarmodafinil, which is a stimulant that has been often used forcancer fatigue. And the second was looking at cannabis compoundsthat have been thought about in thinking about nausea and folks whoare suffering from nausea due to chemotherapy.
So our investigators that looked at armodafinil looked atarmodafinil in patients who had glioma, and they wanted to see thatif they used armodafinil in these patients, whether or not theywould have an improvement in their fatigue. Now in the past, weknow that there have been a number of studies that have looked atdifferent types of treatments for fatigue, everything fromsteroids, to stimulants, to herbs, and what we found is that,consistently, stimulants have not been shown to improve fatigue.The things that have been shown to improve fatigue in small studiesinclude steroids as well as American ginseng. Unfortunately, thiswas yet another negative study, and what we see here is thatarmodafinil did not improve fatigue and in fact, at the dose of 250milligrams, might have increased insomnia or trouble sleeping. Andso with that, I think we would make the assumption that we probablyneed to rethink our approach with stimulants in cancer-relatedfatigue and, for the majority of our patients, would make thedecision that stimulants may not be the best course to improvefatigue.
On a positive note, we did look at patients who were receivingchemotherapy, and, in an Australian study, what they looked at waswhether the addition of a THC plus CBD compound - now, this wasboth THC and CBD 1-to-1 - could improve nausea. And what they foundis that, for these patients who all received the normalprophylaxis-- so they got Zofran. They got a D2 receptorantagonist, such as Compazine. If you added the THC-CBD compound,those patients actually had better nausea control, which wasfantastic. However, they did also have some side effects from theTHC-CBD, including dizziness, sedation, and disorientation. Yetdespite these side effects, the patients really felt better, and sothey were likely to continue using the cannabis. And they wouldactually choose to continue using the cannabis.
Moving on to a different note, there were a variety of differentstudies that looked at risk assessment, and can we actuallyidentify which patients would benefit most from which intervention?And there was a couple of different types of studies here. Onelooked at the utilization of patient-reported outcomes to seewhether or not we can identify patients who may be at more at riskfor poor outcomes. We know Ethan Basch published, a couple yearsago, a landmark study that showed that if you integrated patientreported outcomes, also known as PROs, routinely into cancer care,you could improve survival. So basically, if you looked atsymptoms, evaluated those symptoms, and treated those symptomsearly and often, people lived longer and lived better.
Now, can we use this data that patients give us throughquestionnaires on a regular basis, can we use this data in otherways? And we actually had a few studies here that looked atpatients who had metastatic disease. And Dr. Batra et al. fromCalgary looked at 1,300-plus patients, and what they found was thatpatients who had fewer symptoms tended to do better. And it seemslike a kind of obvious point. If you have more symptoms, you mightdo worse, but I think the routine assessment of symptoms inpatients and utilizing those symptoms is not done. So if we knowthat patients who have fewer symptoms might do better, may be ableto use that data to see whether or not those patients might needmore support or to use that data to see if those patients may notbe the best patients for a clinical trial. Maybe we need to dosymptom control first. So it does help us to risk-stratify andunderstand that patients that have more symptoms tend to have ashorter survival. Patients that have fewer symptoms tend to have abetter survival.
Additionally, we have some really interesting data from Dr.Supriya Mohile at the University of Rochester looking at the use ofa different type of assessment called the geriatric assessment forpatients who are older. Now, we know that the geriatric assessmentcan identify patients who are at high risk for things like falls orcognitive changes or dementia, but what we don't necessarily knowis whether if we routinely use the geriatric assessment, it helpsus with our cancer treatment. And what they did in the study isthey actually randomized patients to do the geriatric assessment.And in 1 arm, they showed the geriatric assessment to theoncologist, and in the other arm, they did not. And what they foundis when they showed the geriatric assessment to the oncologist, thepatient actually received treatment that was probably better forthem based on the findings of their geriatric assessment. Sopatients who were more frail or who had more findings that wouldrequire an assessment and treatment had those things done. So ifthey needed a fall assessment, that got done. If they needed someneuropsych testing for their dementia, that got done. And for thosepatients, the oncologist often would choose to give a slightlylower dose of treatment to prevent further adverse effects. So whatthey found is that if you did a geriatric assessment routinely forolder patients, you could appropriately provide for those needs andactually give them the treatment that is correct for them,preventing adverse events, preventing higher-grade toxicities, andensuring that those patients got the best care.
And then finally, coming to our last group of trials, we had areally great discussion from Amber Barnato from the DartmouthResearch Institute. So it looked at variety of clinical trials ofearly palliative care integration as well as integrating palliativecare through primary palliative care intervention. Now, what's thedifference here? So primary palliative care intervention is whenyou teach clinicians, like your oncologist, to do palliative carethemselves. So that's when they prescribe an opioid for pain, orthat's when they do a goals of care discussion as part of routineadvance care planning. Now, specialist palliative careinterventions look a little different, and that's often when youhave someone who's board-certified in palliative care and hospice,and they come in and do another consultation. And this would beakin to having a cardiologist come help your primary care doctortake care of your hypertension. This would be pulling in anotherteam. So that's the difference between primary and specialistpalliative care. So what we saw here is that there were 2 differenttypes of interventions that were both really interesting.
Now 1 was done in University of Pennsylvania, where theyactually looked at several thousands of patients who had theironcologists get a little nudge through an email that said, "Youknow what? Your patients coming in this week might be at a littlebit of a higher risk for a poor outcome, at a higher risk formortality. And when that happens, it might be good to do someadvance care planning." So that these oncologists that got thisemail nudge, they were more likely to do the right thing by theirpatients. They were more likely to do an advance directive, andthey were more likely to ensure that these patients had their goalsof care documented and their prognosis documents within theircharts. So something as simple as a mortality prediction donethrough a computational tool and an email to those oncologistscould really improve getting the basics done for patients, such asgetting their advance directive done.
Additionally, when we think about, now, specialist palliativecare intervention, Dr. Barnato actually made a really beautifulpoint. She actually looked at a couple of different studies, 1 doneby Tom Smith looking at integrating palliative care in phase 1populations and the other by Dr. Areej El-Jawahri looking atintegrating palliative care into the acute leukemia patientpopulation. And both of these studies were really excellent studiesthat showed quality of life improvement with early integration ofpalliative care. And that is fantastic, and it supports the workthat was led by Jennifer Temel in 2010, where she saw that if youintegrated palliative care early and often, those patients hadbetter quality of life, those caregivers did better, and thosepatients live longer.
And these studies continue to support the fact that earlyintegration of palliative care improves quality of life forpatients from a variety of different walks, whether it's phase 1 oracute leukemia. But what Amber Barnato pointed out was thatpalliative care also does something really different. Whatpalliative care does is it also improves the way that wecommunicate across systems, and what she said, and I think it'simportant to point out, is that we don't often account for that inour metrics. We don't often point out that when a palliative caredoctor talks to an oncologist, it decreases the anxiety of theoncologist. It makes the oncologist deliver better care. Itactually changes the infrastructure of how we deliver care in thesystem, and that improves quality in ways that goes beyond thebiopsychosocial model of just quality of life for patients butreally changes the paradigm of how we deliver care across thesystem. And that we not only need to measure quality of life forpatients but really look at some of these system changes thatpalliative care really helps to propagate and think about how thatcould be measured ongoing.
So it's been another great year for research. We're reallyexcited about what our colleagues are doing out there in palliativecare and supportive care and both in improving systems, improvingrisk assessments, and improving symptoms. We look forward toanother year of research in ASCO 2021. Thank you so much for havingme here today to talk to you a little bit about what we learnedfrom our colleagues and friends.
ASCO: Thank you, Dr. Ramchandran. Learn moreabout the research presented at the ASCO20 Virtual ScientificProgram at www.cancer.net/blog, and subscribeto Cancer.Net podcasts on Apple Podcasts or Google Play foradditional episodes in the Research Round Up series, releasedthroughout the summer.
This Cancer.Net podcast is part of the ASCO Podcast Network.This collection of 9 programs offers insight into the world ofcancer care, covering a range of educational, inspirational, andscientific content. You can find all 9 shows, including this one,at podcast.asco.org.
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