2022 Research Round Up: Head and Neck Cancer, Brain Tumors, and Health Equity

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In the Research Round Up series, ASCO experts and members of the Cancer.Net Editorial Board discuss the most exciting and practice-changing research in their field and explain what it means for people with cancer. In today’s episode, our guests will discuss new research in head and neck cancer, brain tumors, and health 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 new treatment options for locally advanced head and neck cancer. Dr. Rodriguez is a medical oncologist at Seattle Cancer Care Alliance, an Associate Professor in the Division of Medical Oncology at the University of Washington, and an Associate Member for solid tumor clinical research at the Fred Hutchinson Cancer Research Center. She is also the Cancer.Net Associate Editor for Head and Neck Cancers. You can view Dr. Rodriguez’s disclosures at Cancer.Net. Dr. Rodriguez: Hello. My name is Christina Rodriguez. I'm a medical oncologist with a clinical and research focus on head and neck cancer. And today I'm going to discuss research on head and neck cancer that was presented at the most recent 2022 ASCO Annual Meeting. I don't have any relationship to disclose that pertains to the research that I will talk about today. I'd like to discuss 2 abstracts that I thought were practice changing or practice affirming that really addresses some of the key questions that patients and doctors like me have about the treatment of patients with head and neck cancer. So, as you know, most patients with head and neck cancer present with typically locally advanced disease, and most head and neck cancer patients are treated with the intent of curing them most of the time with the use of radiation either as the main treatment or after surgery. And many clinical trials have shown that when we add a chemotherapy called cisplatin to radiation, we improve curative outcomes for patients. But the first abstract that I will talk about, abstract 6003, asks the question "What do we do for patients who are not candidates for cisplatin chemotherapy?" And we know that a significant proportion of our patients will have other medical problems that could make it difficult for us to give chemotherapy and often will result in complications or more toxicity or in side effects for patients. This clinical trial was carried out in India, and it compared radiation alone for patients with head and neck cancer versus radiation given with a non-cisplatin chemotherapy called docetaxel. What's unique about this clinical trial is that it's specifically focused on patients who were not candidates for cisplatin chemotherapy, something that really hasn't been done for this population. Interestingly enough, they found that when we give docetaxel with radiation in these patients, we find that they do better, they live longer, and they feel better based on quality-of-life questionnaires. So I will say that this study, abstract 6003, tells us that even in patients who are not candidates for cisplatin to be given with radiation, there is an alternative treatment that we can use, such as docetaxel given with radiation, that might still improve patient's cure rates for their head and neck cancer. The second study that I think was another interesting study was a clinical trial that asked the question, "Can we give cisplatin in an alternative manner for patients who are undergoing definitive radiation treatment as their main treatment for head and neck cancer?" Like I mentioned, the clinical trials that led to the use of chemoradiation as a standard use cisplatin given in larger doses every 3 weeks, but there's been concern about how well that approach is tolerated by patients. So this particular clinical trial compared patients receiving radiation as curative intense therapy for head and neck cancer with either the cisplatin given every  3 weeks or the cisplatin given at a lower dose once a week. It's important to know that this trial was done in India, where the population is pretty different from what we see in the United States. 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 very similar outcomes. In other words, there didn't seem to be a reduction in the rates of cure when we give chemotherapy every week versus every 3 weeks. And interestingly enough, it looked like from a toxicity or side effect standpoint, the every week seems to be a little bit better tolerated. Patients who got the treatment every 3 weeks also had less need for hospitalization or IV fluids and less utilization of health care resources. I think this is a very interesting finding because it really provides us with what we call high-level data that the weekly administration can work. I think it's important to recognize that the population that it studied for this particular clinical trial really was more an HPV-negative population. That's important to know because the standards for HPV-positive head and neck cancer are generated from larger trials that use cisplatin every 3 weeks. But we are continuing to study this question, and there's actually a large NRG study, HN009, that is asking that question both for the HPV- positive and HPV- negative population. So we are, I think, making strides in terms of asking the questions that allow our patients not only to receive treatment that is highly efficacious but also that limits side effects and toxicity. I will also mention that these trials were completed during the COVID-19 pandemic, which tells you that the dedication of these researchers to complete something like this in such a challenging time is to be commended. That's all I have to say, and thank you for listening to this brief summary of new research in head and neck cancer from the ASCO 2022 Annual Meeting. ASCO: Thank you, Dr. Rodriguez. Next, Dr. Glenn Lesser will discuss 3 studies that looked at new treatments for different types of brain tumors. Dr. Lesser is the inaugural Louise McMichael Miracle Professor and Associate Chief in the section on Hematology and Oncology in the Department of Internal Medicine at Wake Forest Health. He is also the Cancer.Net Associate Editor for Central Nervous System Tumors. You can view Dr. Lesser’s disclosures at Cancer.Net.   Dr. Lesser: Hello. My name is Glenn Lesser, and I'm a professor of medical oncology and the director of medical neuro-oncology at the Wake Forest Baptist Comprehensive Cancer Center in Winston-Salem, North Carolina. I'm also the editor of the brain tumor section for ASCO's Cancer.Net. And today, I would like to briefly discuss several clinically relevant research studies involving patients with brain tumors that were presented at this year's ASCO Scientific Program. Of note, I have no disclosures or relationships relevant to the abstracts I'll be discussing today. The first presentation to talk about is a late-breaking abstract presented by Dr. Eric Bouffet, who described the results of a phase II trial of 2 targeted anticancer agents, dabrafenib and trametinib, in pediatric patients with a kind of brain tumor called a low-grade glioma, which harbored something called a BRAF V600E mutation in their tumor DNA. By way of background, gliomas account for about 45% of all pediatric brain tumors, and the majority of these gliomas are low-grade, which include World Health Organization grade 1 and 2 tumors. Common types of pediatric low-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 been developed to effectively treat these tumors by targeting this mutant BRAF gene. A particular mutation in this gene called a V600E mutation occurs in about 15% to 20% of pediatric low-grade gliomas. The presence of this mutation is thought to lead to an increased risk of progression to a higher grade or a more malignant glioma in these patients, and these mutations in their tumors also predict a less favorable response to chemotherapy. In adults, recent studies in patients with malignant gliomas, papillary craniopharyngiomas, and melanomas containing V600E mutations have shown excellent results, with 1one of several similar 2-drug combinations that target both the V600E mutation and a second pathway that cells use to escape from this BRAF blockade. Now, early pediatric data suggested that one of these pairs of drugs, the combination of dabrafenib and trametinib, was safe and tolerable and had the ability to effectively treat patients whose tumors had the V600E mutation. So with that as background, this study was started and enrolled patients from 12 months to 18 years of age who had a low-grade glioma that contained a BRAF V600E mutation. And it randomized them to receive either the combination of dabrafenib and trametinib, or an older, standard cytotoxic chemotherapy regimen consisting of carboplatin and vincristine. Importantly, these patients were newly diagnosed, and this was the first systemic treatment they got, following their surgery or biopsy. 110 patients were enrolled, with 73 given the new targeted therapy combination and 37 receiving the standard combination. The most common types of tumors that the patients enrolled on this study had included pilocytic astrocytoma, ganglioglioma, and low-grade glioma. The results of this trial were that the patients who received the newer combination, targeted treatment of dabrafenib and trametinib, did substantially better than those who received standard, older cytotoxic chemotherapy. Their overall response rate - that's defined as a complete or partial disappearance of the tumor on MRI scan - was 47% versus 11% in the control arm. When patients who had stable disease by MRI were included, 86% of those on the new combination versus 46% of those patients treated with the older chemotherapy had the so-called best clinical response. Now, a large number of patients responding to dabrafenib and trametinib, remain on treatment and are receiving these drugs with an ongoing imaging and clinical response at the time of this report. Patients receiving the new combination had a median or average progression-free survival of 20 months versus about 7.4 months with the older, standard chemotherapy. The investigators conducting this study also had patients fill out a variety of questionnaires to assess their quality of life while on treatment. Once again, the patients who received dabrafenib and trametinib, on average, experienced an improved quality of life in contrast to those on standard chemo who, on average, had a worse quality of life. The new treatment was also well-tolerated with fewer serious adverse events or side effects when compared with standard chemotherapy. And these side effects were no different than what has been seen in patients without brain tumors who have been treated with this combination, including fevers, headaches, fatigue, skin changes, and lower blood counts. The authors appropriately suggested that these findings demonstrate the importance of molecular testing of these pediatric low-grade glioma tumors at the time of diagnosis and that this combination of dabrafenib and trametinib is a new potential standard of care in those patients who have the BRAF V600E mutant, low-grade tumors. Of note, liquid formulations of these drugs have been developed for those pediatric patients who are unable to swallow capsules or tablets. The second presentation at ASCO highlighted the continued importance of prospective randomized clinical trials in patients with malignant brain tumors. Dr. Jann Sarkaria from the Mayo Clinic presented the long-awaited results of the Alliance for Clinical Trials in Oncology cooperative group phase II/III study of a PARP inhibitor or placebo added to standard temozolomide and radiation in adult patients with newly- diagnosed glioblastoma, and in addition, glioblastomas that had specific molecular finding called MGMT promoter methylation. This change to the DNA of the tumors prevents the MGMT DNA repair enzyme from being made in the tumors and leads to a better outcome with temozolomide treatment. Some very elegant laboratory science had suggested that adding a type of drug called a PARP inhibitor, which also causes defects in DNA repair, could lead to improved killing of glioblastoma tumor cells. So patients with newly- diagnosed glioblastomas, which had MGMT promoter methylation on genomic analysis, were enrolled on this study between December of 2014 and October of 2018. The study was conducted in 2 phases separated by a pre-planned pause after the first group of patients were enrolled, which was the phase II part of the study. This was done in order to allow a preliminary analysis of the outcomes of the treatment arms to make sure that there was a signal of activity that justified moving on to test this treatment in a larger number of patients, the so-called phase III part of the trial. This trial design hopes to minimize the number of patients treated with an inactive drug and save years of drug development time by avoiding large trials that go on for a long time with what turns out to be ineffective drugs. For this trial, 447 patients were eventually treated on this trial. Despite the convincing laboratory evidence and early, promising clinical results that led to the trial moving to the second or phase III portion, the final results showed no statistically significant difference in progression-free or overall survival between the 2 arms, that is, those treated with a PARP inhibitor, and those treated with placebo. I personally was very excited about this study and had hoped that the long wait to hear the results indicated that something good was happening. In addition, several of my patients who were treated on the study did exceedingly well, so I, incorrectly, it turns out, expected positive results from the trial. These negative results are a stark reminder of why we spend lots of time and money and energy performing well-designed clinical trials to determine appropriate treatment strategies for our patients, rather than relying on expert opinion or 1 institution's published experience. This approach turns out to be the best way to fairly test treatment strategies and establish new therapeutic approaches which are truly effective. A final, interesting abstract that was presented at a poster discussion session at ASCO was from the group with the University of Pennsylvania in Philadelphia, and it dealt with the risk of bleeding in patients with brain tumors who had blood clots and were then treated with a newer class of blood thinners or anticoagulants called direct oral anticoagulants, or DOACs for short. It's been known for over 100 years that a variety of types of cancer cause patients to be hypercoagulable, that is, to be predisposed to developing blood clots throughout the venous system. Patients with malignant brain tumors have the highest incidence of all tumors of developing blood clots, which typically occur in the legs, called deep venous thrombosis or DVTs, or in the lungs, called pulmonary emboli or PEs. These clots can lead to a variety of severe and debilitating symptoms, including leg pain, swelling, shortness of breath, heart strain, and even death. For the past 2 to 3 decades, affected patients have typically been treated with a class of medications called low-molecular-weight heparins, which need to be injected under the skin once or twice daily. Over the past decade, a new class of oral anticoagulants called DOACs have generally replaced low-molecular-weight heparins as the primary method of treatment for patients with and without cancer who develop venous blood clots because of their safety, ease of administration, and a lack of requirement for regular blood tests or monitoring. However, little, if any, data has been available to determine the safety of these agents in patients with brain tumors and blood clots, a situation where bleeding into the brain or the brain tumor as a side effect of the anticoagulant could be catastrophic. In fact, this potential risk led to the exclusion of patients with brain tumors from several of the large trials which established the safety of the DOACs. Despite the absence of evidence, the DOACs are now pretty broadly used in brain tumor patients for the reasons described above. So this abstract described a cohort of patients with glioblastoma who developed venous blood clots between 2014 and 2021 while under treatment at Penn. The authors reviewed the medical record to determine the relative efficacy or effectiveness and the toxicity or side effects experienced by patients treated with the low-molecular-weight heparins and with the DOACs, including the rates of bleeding into the brain or the brain tumor. 121 patients were identified who fit these criteria, and the cumulative incidence of clinically significant intracranial hemorrhage, that is, bleeding into the brain or the brain tumor, by 30 days after starting the drugs, was minimal and similar in the 2 groups. When measured at 6 months, 24% of the patients in the low-molecular-weight heparin group had developed intracranial bleeding, and 4 of those patients had died from this bleeding, while none of the 32 patients in the DOAC group experienced this complication. Thus, these investigators felt that their data suggested that there was a lower incidence of clinically important intracranial hemorrhage or bleeding in patients with glioblastoma and venous blood clots who were treated with DOACs as compared to low-molecular-weight heparin. They went on to suggest that the use of DOACs was a safe alternative in patients with glioblastoma. Now clearly, either a prospective trial, a larger trial, or additional retrospective evaluations with a larger number of patients are needed to prove the safety of this approach. But this data is pretty comforting, as the use of these agents is now widespread in patients with high-grade gliomas. The ease of administration of a pill once or twice a day, as compared with potentially lifelong injections once or twice a day, is a major quality of life advantage for our patients. Thank you for listening to this brief summary of new research in neuro-oncology from the 2022 ASCO Annual Meeting. ASCO: Thank you, Dr. Lesser. Finally, Dr. Manali Patel discusses new research focused on reducing disparities in cancer care. Dr. Patel is a medical oncologist and Assistant Professor of Medicine at Stanford University. She is also the Cancer.Net Associate Editor for Health Equity. You can view Dr. Patel’s disclosures at Cancer.Net. Dr. Patel: Today I have the privilege of discussing several really exciting research abstracts that were presented at the 2022 ASCO Annual Meeting. My name is Manali Patel. I'm a thoracic oncologist, meaning I take care of patients and try to provide good care delivery for patients with lung cancer. And I also am a researcher focused on health equity. I have no relevant disclosures for any of the studies that I will be presenting today with the exception of one that I was leading. And there were several wonderful abstracts that were presented on describing disparities and the ongoing state of disparities continuing within cancer care delivery. What I was particularly struck by were many of the abstracts that I'm presenting this morning and this podcast that really focus on what we can do as a nation and what we can do individually in our clinics to try to move towards action to overcoming these inequities. The first abstract I want to present was looking at how the Affordable Care Act and changes in the Affordable Care Act led to differences in mortality or deaths by race and ethnicity following the enactment in California. And this particular study looked at greater than 150,000 people who were diagnosed with breast cancer, colorectal cancer, and cervical cancer. And they evaluated death rates from these cancers both before and after the implementation of the Affordable Care Act. And what they found was that the cancer death rates for everyone was much lower after the Affordable Care Act was passed, but specifically for individuals who had self-identified as Hispanic ethnicity, who also identified as Black and who identified as White. And so what this abstract showed me was that at a larger level and a macro level, our policies that are enforced at the national level really do play a role in terms of how we can overcome disparities in cancer. Our group, as I mentioned before, has worked on really trying to integrate community health workers into care. So this abstract paired with local union organizations in Chicago and in Atlantic City to try to help individuals who self-identified as having been from families that were from low-income households and racial and ethnic minorities to communicate their goals and their preferences for care and to also better their relationships with their clinicians as well as to describe their symptoms. And what we found in this randomized trial was that for individuals who received this community health advocate who helped them to better engage with their clinician and who also helped them to describe the symptoms that they were experiencing as well as receive community resources such as food boxes if they were food insecure or be connected to household agencies if they were having difficulties with housing, we found a significant improvement in quality of life, but we also found reductions in the use of the hospital unnecessarily. We also found that this translated into reductions in total cost of care, thereby reducing the amount of out-of-pocket costs these individuals were spending on their cancer care. One of the other abstracts that I thought really was reflective of the many different ways that we can move towards action was an abstract which looked at during the pandemic, trying to reduce the number of times people need to come in for mammograms, their biopsies, and then any further testing that they needed after their biopsy. And this particular study evaluated what was called a same-day biopsy service, which layered on a same-day mammogram reading program. So at this particular institution, they had already implemented when you came in to get your mammogram as a woman or a man, you would have a read on the same day. So you did not have to wait to find out what your results were. And what they did further to push better care was that they layered on on that same day you could get your biopsy. So almost a one-stop shop. And what they found was that for everyone, regardless of race and ethnicity, the time to biopsies decreased by almost half. And the median days, for example, from an abnormal mammogram to obtaining a biopsy, meaning a sample of that tissue, that it decreased from 10 days median to 5 days. And particular patient populations did much better. And so they were able to show that when you do interventions that move the care to provide better care for everyone, everyone benefits, but particularly our patient populations who identify as racial and ethnic minorities who were more likely to experience delays in care, they also received some benefit from this intervention. The last study I want to highlight is work which looked at how to improve specialized services for people who would otherwise not receive those. And this particular study looked at stem cell transplantation for people with blood cancers. And what they found was that these services are often only offered in very tertiary centers, so places that may not be as accessible, large institutions that a lot of people may not have access to receiving care. So what they did was they partnered with this large academic institution so that they could build a pathway for individuals who would otherwise not get stem cell transplantation so that they could have access to those services. And it was really a multipronged approach where they not only educated the clinicians in the community practice about the effort, but they also educated the institution-level clinicians about the effort. They also provided shared medical records, which oftentimes in practice, we don't share our medical records with other clinics. And what they were able to do was to convince these clinics and the institution, let's share the medical records so that then you can have access to seeing what's happening for patients that are diagnosed in the community. And then that way we can both document, we can both have access in the community as well as in the institution where they're receiving the specialized service so that there's better communication. They also provided a navigator for each patient that would help each patient to identify any sort of barriers that they may experience to receiving stem cell transplantation. And then they offered telemedicine, which allowed for individuals to receive specialized services in the comforts of their own home without having to travel after the stem cell transplantation had occurred. And what they found was that usually in the institution, most individuals were more affluent. So they had higher levels of socioeconomic status. But after the intervention, individuals that were referred from this community clinic made it such that the affluence really decreased so that it was showing that people who wouldn't otherwise have access, who had identified as having low income, were now able to receive those services and had been receiving transplantation. I think that these studies really do move us towards a new paradigm of taking action on the many disparities that we know continue to happen. I really appreciate you all for listening to this brief summary of the new research on health equity from the 2022 ASCO Annual Meeting, and I hope to see you next year. ASCO: Thank you, Dr. Patel. 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. 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