Aug 25, 2022
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In the Research Round Up series, ASCO experts andmembers of the Cancer.Net Editorial Board discuss the most excitingand practice-changing research in their field and explain what itmeans for people with cancer. In today’s episode, our guests willdiscuss new research in head and neck cancer, brain tumors, andhealth equity that was presented at the 2022 ASCO Annual Meeting,held June 3-7 in Chicago, Illinois.
First, Dr. Cristina Rodriguez will discuss 2 studies on newtreatment options for locally advanced head and neck cancer.
Dr. Rodriguez is a medical oncologist at Seattle Cancer CareAlliance, an Associate Professor in the Division of MedicalOncology at the University of Washington, and an Associate Memberfor solid tumor clinical research at the Fred Hutchinson CancerResearch Center. She is also the Cancer.Net Associate Editor forHead and Neck Cancers.
You can view Dr. Rodriguez’s disclosures at Cancer.Net.
Dr. Rodriguez: Hello. My name is ChristinaRodriguez. I'm a medical oncologist with a clinical and researchfocus on head and neck cancer. And today I'm going to discussresearch on head and neck cancer that was presented at the mostrecent 2022 ASCO Annual Meeting. I don't have any relationship todisclose that pertains to the research that I will talk abouttoday. I'd like to discuss 2 abstracts that I thought were practicechanging or practice affirming that really addresses some of thekey questions that patients and doctors like me have about thetreatment of patients with head and neck cancer. So, as you know,most patients with head and neck cancer present with typicallylocally advanced disease, and most head and neck cancer patientsare treated with the intent of curing them most of the time withthe use of radiation either as the main treatment or after surgery.And many clinical trials have shown that when we add a chemotherapycalled cisplatin to radiation, we improve curative outcomes forpatients.
But the first abstract that I will talk about, abstract 6003,asks the question "What do we do for patients who are notcandidates for cisplatin chemotherapy?" And we know that asignificant proportion of our patients will have other medicalproblems that could make it difficult for us to give chemotherapyand often will result in complications or more toxicity or in sideeffects for patients. This clinical trial was carried out in India,and it compared radiation alone for patients with head and neckcancer versus radiation given with a non-cisplatin chemotherapycalled docetaxel. What's unique about this clinical trial is thatit's specifically focused on patients who were not candidates forcisplatin chemotherapy, something that really hasn't been done forthis population. Interestingly enough, they found that when we givedocetaxel with radiation in these patients, we find that they dobetter, they live longer, and they feel better based onquality-of-life questionnaires.
So I will say that this study, abstract 6003, tells us that evenin patients who are not candidates for cisplatin to be given withradiation, there is an alternative treatment that we can use, suchas docetaxel given with radiation, that might still improvepatient's cure rates for their head and neck cancer.
The second study that I think was another interesting study wasa clinical trial that asked the question, "Can we give cisplatin inan alternative manner for patients who are undergoing definitiveradiation treatment as their main treatment for head and neckcancer?" Like I mentioned, the clinical trials that led to the useof chemoradiation as a standard use cisplatin given in larger dosesevery 3 weeks, but there's been concern about how well thatapproach is tolerated by patients. So this particular clinicaltrial compared patients receiving radiation as curative intensetherapy for head and neck cancer with either the cisplatin givenevery 3 weeks or the cisplatin given at a lower dose once aweek.
It's important to know that this trial was done in India, wherethe population is pretty different from what we see in the UnitedStates. These are mostly patients who have HPV-negative cancers,mostly cancers acquired through exposures like tobacco and alcohol.And what they found was that these 2 groups of patients had verysimilar outcomes. In other words, there didn't seem to be areduction in the rates of cure when we give chemotherapy every weekversus every 3 weeks. And interestingly enough, it looked like froma toxicity or side effect standpoint, the every week seems to be alittle bit better tolerated. Patients who got the treatment every 3weeks also had less need for hospitalization or IV fluids and lessutilization of health care resources.
I think this is a very interesting finding because it reallyprovides us with what we call high-level data that the weeklyadministration can work. I think it's important to recognize thatthe population that it studied for this particular clinical trialreally was more an HPV-negative population. That's important toknow because the standards for HPV-positive head and neck cancerare generated from larger trials that use cisplatin every 3 weeks.But we are continuing to study this question, and there's actuallya large NRG study, HN009, that is asking that question both for theHPV- positive and HPV- negative population. So we are, I think,making strides in terms of asking the questions that allow ourpatients not only to receive treatment that is highly efficaciousbut also that limits side effects and toxicity. I will also mentionthat these trials were completed during the COVID-19 pandemic,which tells you that the dedication of these researchers tocomplete something like this in such a challenging time is to becommended. That's all I have to say, and thank you for listening tothis brief summary of new research in head and neck cancer from theASCO 2022 Annual Meeting.
ASCO: Thank you, Dr. Rodriguez.
Next, Dr. Glenn Lesser will discuss 3 studies that looked at newtreatments for different types of brain tumors.
Dr. Lesser is the inauguralLouise McMichaelMiracleProfessor and Associate Chief in the section onHematology and Oncology in the Department of Internal Medicine atWake Forest Health. He is also the Cancer.Net Associate Editor forCentral Nervous System Tumors.
You can view Dr. Lesser’s disclosures at Cancer.Net.
Dr. Lesser: Hello. My name is Glenn Lesser, andI'm a professor of medical oncology and the director of medicalneuro-oncology at the Wake Forest Baptist Comprehensive CancerCenter in Winston-Salem, North Carolina. I'm also the editor of thebrain tumor section for ASCO's Cancer.Net. And today, I would liketo briefly discuss several clinically relevant research studiesinvolving patients with brain tumors that were presented at thisyear's ASCO Scientific Program. Of note, I have no disclosures orrelationships relevant to the abstracts I'll be discussingtoday.
The first presentation to talk about is a late-breaking abstractpresented by Dr. Eric Bouffet, who described the results of a phaseII trial of 2 targeted anticancer agents, dabrafenib andtrametinib, in pediatric patients with a kind of brain tumor calleda low-grade glioma, which harbored something called a BRAF V600Emutation in their tumor DNA. By way of background, gliomas accountfor about 45% of all pediatric brain tumors, and the majority ofthese gliomas are low-grade, which include World HealthOrganization grade 1 and 2 tumors. Common types of pediatriclow-grade gliomas include pilocytic astrocytomas, gangliogliomas,and low-grade gliomas that are not otherwise specified. Now,mutations in the BRAF gene are common in certain kinds of cancers,particularly melanoma, and novel oral targeted therapies have beendeveloped to effectively treat these tumors by targeting thismutant BRAF gene. A particular mutation in this gene called a V600Emutation occurs in about 15% to 20% of pediatric low-grade gliomas.The presence of this mutation is thought to lead to an increasedrisk of progression to a higher grade or a more malignant glioma inthese patients, and these mutations in their tumors also predict aless favorable response to chemotherapy.
In adults, recent studies in patients with malignant gliomas,papillary craniopharyngiomas, and melanomas containing V600Emutations have shown excellent results, with 1one of severalsimilar 2-drug combinations that target both the V600E mutation anda second pathway that cells use to escape from this BRAF blockade.Now, early pediatric data suggested that one of these pairs ofdrugs, the combination of dabrafenib and trametinib, was safe andtolerable and had the ability to effectively treat patients whosetumors had the V600E mutation. So with that as background, thisstudy was started and enrolled patients from 12 months to 18 yearsof age who had a low-grade glioma that contained a BRAF V600Emutation. And it randomized them to receive either the combinationof dabrafenib and trametinib, or an older, standard cytotoxicchemotherapy regimen consisting of carboplatin and vincristine.Importantly, these patients were newly diagnosed, and this was thefirst systemic treatment they got, following their surgery orbiopsy. 110 patients were enrolled, with 73 given the new targetedtherapy combination and 37 receiving the standard combination. Themost common types of tumors that the patients enrolled on thisstudy had included pilocytic astrocytoma, ganglioglioma, andlow-grade glioma.
The results of this trial were that the patients who receivedthe newer combination, targeted treatment of dabrafenib andtrametinib, did substantially better than those who receivedstandard, older cytotoxic chemotherapy. Their overall response rate- that's defined as a complete or partial disappearance of thetumor on MRI scan - was 47% versus 11% in the control arm. Whenpatients who had stable disease by MRI were included, 86% of thoseon the new combination versus 46% of those patients treated withthe older chemotherapy had the so-called best clinical response.Now, a large number of patients responding to dabrafenib andtrametinib, remain on treatment and are receiving these drugs withan ongoing imaging and clinical response at the time of thisreport. Patients receiving the new combination had a median oraverage progression-free survival of 20 months versus about 7.4months with the older, standard chemotherapy.
The investigators conducting this study also had patients fillout a variety of questionnaires to assess their quality of lifewhile on treatment. Once again, the patients who receiveddabrafenib and trametinib, on average, experienced an improvedquality of life in contrast to those on standard chemo who, onaverage, had a worse quality of life. The new treatment was alsowell-tolerated with fewer serious adverse events or side effectswhen compared with standard chemotherapy. And these side effectswere no different than what has been seen in patients without braintumors who have been treated with this combination, includingfevers, headaches, fatigue, skin changes, and lower blood counts.The authors appropriately suggested that these findings demonstratethe importance of molecular testing of these pediatric low-gradeglioma tumors at the time of diagnosis and that this combination ofdabrafenib and trametinib is a new potential standard of care inthose patients who have the BRAF V600E mutant, low-grade tumors. Ofnote, liquid formulations of these drugs have been developed forthose pediatric patients who are unable to swallow capsules ortablets.
The second presentation at ASCO highlighted the continuedimportance of prospective randomized clinical trials in patientswith malignant brain tumors. Dr. Jann Sarkaria from the Mayo Clinicpresented the long-awaited results of the Alliance for ClinicalTrials in Oncology cooperative group phase II/III study of a PARPinhibitor or placebo added to standard temozolomide and radiationin adult patients with newly- diagnosed glioblastoma, and inaddition, glioblastomas that had specific molecular finding calledMGMT promoter methylation. This change to the DNA of the tumorsprevents the MGMT DNA repair enzyme from being made in the tumorsand leads to a better outcome with temozolomide treatment. Somevery elegant laboratory science had suggested that adding a type ofdrug called a PARP inhibitor, which also causes defects in DNArepair, could lead to improved killing of glioblastoma tumor cells.So patients with newly- diagnosed glioblastomas, which had MGMTpromoter methylation on genomic analysis, were enrolled on thisstudy between December of 2014 and October of 2018. The study wasconducted in 2 phases separated by a pre-planned pause after thefirst group of patients were enrolled, which was the phase II partof the study. This was done in order to allow a preliminaryanalysis of the outcomes of the treatment arms to make sure thatthere was a signal of activity that justified moving on to testthis treatment in a larger number of patients, the so-called phaseIII part of the trial. This trial design hopes to minimize thenumber of patients treated with an inactive drug and save years ofdrug development time by avoiding large trials that go on for along time with what turns out to be ineffective drugs.
For this trial, 447 patients were eventually treated on thistrial. Despite the convincing laboratory evidence and early,promising clinical results that led to the trial moving to thesecond or phase III portion, the final results showed nostatistically significant difference in progression-free or overallsurvival between the 2 arms, that is, those treated with a PARPinhibitor, and those treated with placebo. I personally was veryexcited about this study and had hoped that the long wait to hearthe results indicated that something good was happening. Inaddition, several of my patients who were treated on the study didexceedingly well, so I, incorrectly, it turns out, expectedpositive results from the trial. These negative results are a starkreminder of why we spend lots of time and money and energyperforming well-designed clinical trials to determine appropriatetreatment strategies for our patients, rather than relying onexpert opinion or 1 institution's published experience. Thisapproach turns out to be the best way to fairly test treatmentstrategies and establish new therapeutic approaches which are trulyeffective.
A final, interesting abstract that was presented at a posterdiscussion session at ASCO was from the group with the Universityof Pennsylvania in Philadelphia, and it dealt with the risk ofbleeding in patients with brain tumors who had blood clots and werethen treated with a newer class of blood thinners or anticoagulantscalled direct oral anticoagulants, or DOACs for short. It's beenknown for over 100 years that a variety of types of cancer causepatients to be hypercoagulable, that is, to be predisposed todeveloping blood clots throughout the venous system. Patients withmalignant brain tumors have the highest incidence of all tumors ofdeveloping blood clots, which typically occur in the legs, calleddeep venous thrombosis or DVTs, or in the lungs, called pulmonaryemboli or PEs. These clots can lead to a variety of severe anddebilitating symptoms, including leg pain, swelling, shortness ofbreath, heart strain, and even death. For the past 2 to 3 decades,affected patients have typically been treated with a class ofmedications called low-molecular-weight heparins, which need to beinjected under the skin once or twice daily. Over the past decade,a new class of oral anticoagulants called DOACs have generallyreplaced low-molecular-weight heparins as the primary method oftreatment for patients with and without cancer who develop venousblood clots because of their safety, ease of administration, and alack of requirement for regular blood tests or monitoring. However,little, if any, data has been available to determine the safety ofthese agents in patients with brain tumors and blood clots, asituation where bleeding into the brain or the brain tumor as aside effect of the anticoagulant could be catastrophic.
In fact, this potential risk led to the exclusion of patientswith brain tumors from several of the large trials whichestablished the safety of the DOACs. Despite the absence ofevidence, the DOACs are now pretty broadly used in brain tumorpatients for the reasons described above. So this abstractdescribed a cohort of patients with glioblastoma who developedvenous blood clots between 2014 and 2021 while under treatment atPenn. The authors reviewed the medical record to determine therelative efficacy or effectiveness and the toxicity or side effectsexperienced by patients treated with the low-molecular-weightheparins and with the DOACs, including the rates of bleeding intothe brain or the brain tumor. 121 patients were identified who fitthese criteria, and the cumulative incidence of clinicallysignificant intracranial hemorrhage, that is, bleeding into thebrain or the brain tumor, by 30 days after starting the drugs, wasminimal and similar in the 2 groups. When measured at 6 months, 24%of the patients in the low-molecular-weight heparin group haddeveloped intracranial bleeding, and 4 of those patients had diedfrom this bleeding, while none of the 32 patients in the DOAC groupexperienced this complication. Thus, these investigators felt thattheir data suggested that there was a lower incidence of clinicallyimportant intracranial hemorrhage or bleeding in patients withglioblastoma and venous blood clots who were treated with DOACs ascompared to low-molecular-weight heparin. They went on to suggestthat the use of DOACs was a safe alternative in patients withglioblastoma. Now clearly, either a prospective trial, a largertrial, or additional retrospective evaluations with a larger numberof patients are needed to prove the safety of this approach. Butthis data is pretty comforting, as the use of these agents is nowwidespread in patients with high-grade gliomas.
The ease of administration of a pill once or twice a day, ascompared with potentially lifelong injections once or twice a day,is a major quality of life advantage for our patients. Thank youfor listening to this brief summary of new research inneuro-oncology from the 2022 ASCO Annual Meeting.
ASCO: Thank you, Dr. Lesser.
Finally, Dr. Manali Patel discusses new research focused onreducing disparities in cancer care.
Dr. Patel is a medical oncologist and Assistant Professor ofMedicine at Stanford University. She is also the Cancer.NetAssociate Editor for Health Equity.
You can view Dr. Patel’s disclosures at Cancer.Net.
Dr. Patel: Today I have the privilege ofdiscussing several really exciting research abstracts that werepresented at the 2022 ASCO Annual Meeting. My name is Manali Patel.I'm a thoracic oncologist, meaning I take care of patients and tryto provide good care delivery for patients with lung cancer. And Ialso am a researcher focused on health equity. I have no relevantdisclosures for any of the studies that I will be presenting todaywith the exception of one that I was leading.
And there were several wonderful abstracts that were presentedon describing disparities and the ongoing state of disparitiescontinuing within cancer care delivery. What I was particularlystruck by were many of the abstracts that I'm presenting thismorning and this podcast that really focus on what we can do as anation and what we can do individually in our clinics to try tomove towards action to overcoming these inequities. The firstabstract I want to present was looking at how the Affordable CareAct and changes in the Affordable Care Act led to differences inmortality or deaths by race and ethnicity following the enactmentin California. And this particular study looked at greater than150,000 people who were diagnosed with breast cancer, colorectalcancer, and cervical cancer. And they evaluated death rates fromthese cancers both before and after the implementation of theAffordable Care Act. And what they found was that the cancer deathrates for everyone was much lower after the Affordable Care Act waspassed, but specifically for individuals who had self-identified asHispanic ethnicity, who also identified as Black and who identifiedas White. And so what this abstract showed me was that at a largerlevel and a macro level, our policies that are enforced at thenational level really do play a role in terms of how we canovercome disparities in cancer.
Our group, as I mentioned before, has worked on really trying tointegrate community health workers into care. So this abstractpaired with local union organizations in Chicago and in AtlanticCity to try to help individuals who self-identified as having beenfrom families that were from low-income households and racial andethnic minorities to communicate their goals and their preferencesfor care and to also better their relationships with theirclinicians as well as to describe their symptoms. And what we foundin this randomized trial was that for individuals who received thiscommunity health advocate who helped them to better engage withtheir clinician and who also helped them to describe the symptomsthat they were experiencing as well as receive community resourcessuch as food boxes if they were food insecure or be connected tohousehold agencies if they were having difficulties with housing,we found a significant improvement in quality of life, but we alsofound reductions in the use of the hospital unnecessarily. We alsofound that this translated into reductions in total cost of care,thereby reducing the amount of out-of-pocket costs theseindividuals were spending on their cancer care.
One of the other abstracts that I thought really was reflectiveof the many different ways that we can move towards action was anabstract which looked at during the pandemic, trying to reduce thenumber of times people need to come in for mammograms, theirbiopsies, and then any further testing that they needed after theirbiopsy. And this particular study evaluated what was called asame-day biopsy service, which layered on a same-day mammogramreading program. So at this particular institution, they hadalready implemented when you came in to get your mammogram as awoman or a man, you would have a read on the same day. So you didnot have to wait to find out what your results were. And what theydid further to push better care was that they layered on on thatsame day you could get your biopsy. So almost a one-stop shop. Andwhat they found was that for everyone, regardless of race andethnicity, the time to biopsies decreased by almost half. And themedian days, for example, from an abnormal mammogram to obtaining abiopsy, meaning a sample of that tissue, that it decreased from 10days median to 5 days. And particular patient populations did muchbetter. And so they were able to show that when you dointerventions that move the care to provide better care foreveryone, everyone benefits, but particularly our patientpopulations who identify as racial and ethnic minorities who weremore likely to experience delays in care, they also received somebenefit from this intervention.
The last study I want to highlight is work which looked at howto improve specialized services for people who would otherwise notreceive those. And this particular study looked at stem celltransplantation for people with blood cancers. And what they foundwas that these services are often only offered in very tertiarycenters, so places that may not be as accessible, largeinstitutions that a lot of people may not have access to receivingcare. So what they did was they partnered with this large academicinstitution so that they could build a pathway for individuals whowould otherwise not get stem cell transplantation so that theycould have access to those services. And it was really amultipronged approach where they not only educated the cliniciansin the community practice about the effort, but they also educatedthe institution-level clinicians about the effort. They alsoprovided shared medical records, which oftentimes in practice, wedon't share our medical records with other clinics. And what theywere able to do was to convince these clinics and the institution,let's share the medical records so that then you can have access toseeing what's happening for patients that are diagnosed in thecommunity. And then that way we can both document, we can both haveaccess in the community as well as in the institution where they'rereceiving the specialized service so that there's bettercommunication. They also provided a navigator for each patient thatwould help each patient to identify any sort of barriers that theymay experience to receiving stem cell transplantation. And thenthey offered telemedicine, which allowed for individuals to receivespecialized services in the comforts of their own home withouthaving to travel after the stem cell transplantation had occurred.And what they found was that usually in the institution, mostindividuals were more affluent. So they had higher levels ofsocioeconomic status. But after the intervention, individuals thatwere referred from this community clinic made it such that theaffluence really decreased so that it was showing that people whowouldn't otherwise have access, who had identified as having lowincome, were now able to receive those services and had beenreceiving transplantation.
I think that these studies really do move us towards a newparadigm of taking action on the many disparities that we knowcontinue to happen. I really appreciate you all for listening tothis brief summary of the new research on health equity from the2022 ASCO Annual Meeting, and I hope to see you next year.
ASCO: Thank you, Dr. Patel.
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