New ASCO Guidelines for Recurrent and Metastatic Head and Neck Cancers
Emrullah Yilmaz, MD, PhD, an oncologist at Cleveland Clinic Taussig Cancer Institute specializing in head and neck cancers, joins the Cancer Advances podcast to discuss new ASCO guidelines for recurrent and metastatic head and neck cancers. Listen as Dr. Yilmaz explains how the guidelines focus on biomarkers, tumor mutation burdens, and how they will impact patient care.
New ASCO Guidelines for Recurrent and Metastatic Head and Neck Cancers
Dale Shepard, MD, PhD: Cancer Advances, a Cleveland Clinic podcast for medical professionals exploring the latest innovative research and clinical advances in the field of oncology.
Thank you for joining us for another episode of Cancer Advances. I'm your host, Dr. Dale Shepard, a medical oncologist here at Cleveland Clinic overseeing our Taussig phase one and sarcoma programs. Today, I'm happy to be joined by Dr. Emrullah Yilmaz, an oncologist here at the Cleveland Clinic Taussig Cancer Institute, treating head and neck cancers. He's here today to talk to us about new guidelines for recurrent and metastatic head and neck cancers. So welcome.
Emrullah Yilmaz, MD, PhD: Thank you so much. Thanks for having me.
Dale Shepard, MD, PhD: Absolutely. So, give us a little overview. What do you do here at Cleveland Clinic?
Emrullah Yilmaz, MD, PhD: Yeah, I'm a medical oncologist and I specialize in treating patients with head and neck cancers, and I collaborate with other colleagues in head and neck surgery and radiation oncology.
Dale Shepard, MD, PhD: All right. So, we have a number of people that might be listening in that may not necessarily understand what head and neck cancers, you know, lungs and organs, but head and neck, what does it entail? Tell us a little bit.
Emrullah Yilmaz, MD, PhD: Yeah, sure. So, head and neck cancers are the cancers that originate mostly from the oral cavity, oral fillings, tonsil area, larynx around the voice box and sometimes, rarely, and the salivary gland and the sinuses. So, these are the cancers that a lot of times present themselves as a lump in the neck area. And most of the time these are treated with local treatments like surgery, radiation and sometimes requiring chemotherapy as well. But unfortunately, sometimes the treatments don't work and there're recurrences that required the treatments such as immunotherapy or the patients present with metastatic disease requiring immunotherapies upfront as well.
Dale Shepard, MD, PhD: OK. So, we're going to talk a little bit about some guidelines. So, give us a little bit of an idea what the current state was, what sort of the questions were in terms of how to approach these tumors and why we needed some updated guidelines.
Emrullah Yilmaz, MD, PhD: Yeah. So, as I said, most of the time we treat these cancers with local treatments and that requires input from a lot of different physicians like surgeons, radiation oncologists and medical oncologists. The patients undergo either surgery, radiation, chemotherapy, but if they have any recurrence, then we do immunotherapy at that time. Or if there's any metastasis upfront, then we do immunotherapy. So actually, we have been using immunotherapy for head and neck cancers for many years. And immunotherapy, meaning most of the time with the checkpoint inhibitors have been approved for a lot of cancers for several years and head and neck cancers were among the first cancers that were FDA approved for immunotherapy, as the first approvals came around 2016. So, the first approvals were for pembrolizumab and nivolumab, and we've been using immunotherapy for mostly the setting that we call platinum refractory disease, which if the patients have a recurrence after platinum-based chemotherapy within six months.
But in the last couple years, we had recent findings that there were approvals in the frontline settings depending on the biomarkers. And, in non-squamous cell carcinoma, such as nasopharyngeal cancers, there has been more advances and also there has been needed to approach the patients for rare cancers. So that's why since this has become a little bit wider area, so that there has been a need for building a guideline to put together all these findings and to have an evidence-based approach.
Dale Shepard, MD, PhD: And when you mention biomarkers, what kind of biomarkers are we talking about?
Emrullah Yilmaz, MD, PhD: Yeah, so the title also includes biomarkers. So that's why we wanted to focus on the biomarker for this guideline. So, the primary biomarker is PD-L1. And PD-L1 is used to choose immunotherapy for a lot of cancers. And for most cancers, for example, TPS, which is the tumor proportion score is used as the biomarker, but for head and neck clinical trials, CPS, which is combined proportion score is used. So that's why we wanted to focus on the biomarkers part, and we had a different section, the guideline had a different section for just focus on the biomarker just to make sure the right biomarker is requested by the oncologist and sent out by the pathologist. So that is one biomarker.
And the other biomarker is the tumor mutational burden. And that is another biomarker emerging as a potential to predict response to immunotherapy. And that becomes a little bit more important for the rare head and neck cancers. Because in the head and neck area we sometimes see rare tumors, for example, salivary gland cancers, we don't have a lot of treatment options beyond chemotherapy if they don't have certain targets. And the clinical trial that led to immunotherapy approval for the high tumor mutational burden patients included some salivary cancer patients as well. So that's why we wanted to include the tumor mutation burden and focus on that one as well. So that's why this guideline had a special focus on PD-L1 and tumor mutational burden as biomarker.
Dale Shepard, MD, PhD: Excellent. So how did you guys go about putting together information? It's a rare cancer, there may not be specific trials in particular subtypes of head and neck cancers. How did you guys' approach develop the guidelines?
Emrullah Yilmaz, MD, PhD: So, for the head and neck squamous cell carcinoma, where there are large, randomized trials, first, the guideline focuses on those trials just to make sure that those randomized trials, large trials, phase two, three trials are used as the evidence. And then if there is no large, randomized trials, then for those rare tumors then, again, looking at those trials that includes a lot of cancers that has more biomarker-based trials, such as that Keynote-158 trial that had led to high tumor mutational burden cancer patients with any cancer type. So those are the things that we wanted to look at just to make sure that we capture most of the relevant findings to the rare cancers.
Dale Shepard, MD, PhD: And I guess just to clarify, the guidelines we're talking about, these are through ASCO?
Emrullah Yilmaz, MD, PhD: These are through ASCO, correct.
Dale Shepard, MD, PhD: Because there's also people who might think about NCCN guidelines, but these, we're talking today about ASCO guidelines.
Emrullah Yilmaz, MD, PhD: Correct. Yeah, this is the ASCO guideline for immunotherapy for recurrent metastatic head and neck cancers.
Dale Shepard, MD, PhD: And when you go to put together a group like this and come up with guidelines, who else is involved, how many people, what kind of disciplines?
Emrullah Yilmaz, MD, PhD: So, for treating the patients like these, a lot of different physicians are involved. So that's why this guideline included medical oncologist, pathologists, since the biomarkers were involved, surgeons, head and neck surgeons, radiation oncologist, and more important the patient representative as well, just to make sure that any recommendations are coming up relevant to the patients at the same time.
Dale Shepard, MD, PhD: Excellent. So, with the newer guidelines, what are some of the things in the new guidelines that will make the biggest impact, do you think, on patient care?
Emrullah Yilmaz, MD, PhD: So, one of the practices changing head and neck cancers was in the frontline settings. So that was for the patients who presented with metastatic disease who haven't had any chemotherapy or who had recurrence more than six months from prior chemotherapy who are eligible for getting another chemotherapy as well. So, for those patients, if they have a high PD-L1 score, then they can get immunotherapy alone or chemotherapy and immunotherapy. And if they have a low PD-L1 score, then they can get chemo immunotherapy. So, this guideline has an algorithm to help the physicians with how to approach the patients depending on the PD-L1 score.
And the other one is also there have been a lot of new findings for the patients with nasopharyngeal carcinoma. And these studies came mostly from Asia. And a lot of times since nasopharyngeal carcinomas are endemic in Asia, most of the studies usually come from Asia and we try to adopt those treatments for our patients here. So that's why we had a chapter for an algorithm for the patients with the nasopharyngeal carcinoma and how to apply those immunotherapy approaches with the chemotherapy combinations for nasopharyngeal carcinoma as well.
Dale Shepard, MD, PhD: When we think about these guidelines, how do you think these guidelines specifically will help us manage patients here at Cleveland Clinic?
Emrullah Yilmaz, MD, PhD: So, in our multidisciplinary head and neck clinic, we see a lot of patients with head and neck cancers, and we also have a large healthcare system that we are seeing a lot of head and neck cancer patients. And we try to use the most evidence-based practice. So that's why these guidelines help us from that perspective. And most recently, we also looked at our experience in Cleveland Clinic and had a recent publication last month actually looking at our experience with immunotherapy patients, head and neck cancer patients, getting immunotherapy. So, among our patients in Cleveland clinic health system getting immunotherapy, we have seen more than 250 patients getting immunotherapy with head and neck cancers. And we compared our outcomes to the clinical trials, such as Keynote-40 and Keynote-48, that these guidelines actually referred to. And our outcomes are actually very similar to these clinical trials. So that's why it helps us to try to make sure that we continue to use evidence-based treatment for our patients. And at the same time, we continue to try to enroll patients to immunotherapy clinical trials and try to find the best clinical trial for our patients at the same time.
Dale Shepard, MD, PhD: That's great. So, it's great to see our outcomes are so close to trials because, you know, have sort of handpicked people in trials and then you think about real world patients, sometimes you don't get the same outcomes. So, it's good to see that we have such good outcomes.
Emrullah Yilmaz, MD, PhD: Exactly. And that was our purpose, to look at our outcomes, just to make sure that the real-world experience actually reflects the clinical trials at the same time.
Dale Shepard, MD, PhD: Now, I guess another quick, so some tumor types of patients are more likely to be treated on main campus rather than in the region within head and neck. Are most patients being treated on the main campus or how much regional involvement do we get with treating head and neck cancers?
Emrullah Yilmaz, MD, PhD: I think it's a mix, but even if the patients are treated in the region, sometimes we still get referral and see the patients and they might go back and treat it in the region. So that's why there's a mix of patients getting treated on both sites.
Dale Shepard, MD, PhD: And then things like these guidelines and our care paths and things like that would be, of course, helpful.
Emrullah Yilmaz, MD, PhD: Exactly.
Dale Shepard, MD, PhD: For those physicians as well.
Emrullah Yilmaz, MD, PhD: Yes.
Dale Shepard, MD, PhD: So, when you get a wide range of people, disciplines, practice styles, for lack of a better way to put it, were there any surprises? So, when you had discussions, were there any particularly contentious points where people had differing views on how to treat?
Emrullah Yilmaz, MD, PhD: Definitely. So that's why that was really a great experience to work with different people. Look, these people in the panel of the guideline were all experts in their fields and sometimes there's a little bit fine differences in different, in the practice, but at the end it all came to the evidence about what evidence says and then the consensus about the agreement on making the recommendation. So that was from that part that great experience from my end.
Dale Shepard, MD, PhD: And then how do these guidelines fit in line with, I mentioned NCCN guidelines, are this kind of consistent or how should one approach a patient when you are faced with differing sets of guidelines? You know, you look at NCCN, you look at ASCO, how would a physician look at those and make decisions?
Emrullah Yilmaz, MD, PhD: So NCCN guidelines are a little bit more general guidelines how to approach, and for example, head and neck cancers in general. But these ASCO guidelines give specific recommendations and specific settings. For example, this is for more detailed guidelines for how to treat patients with immunotherapy and recurrent metastatic head and neck cancers.
Dale Shepard, MD, PhD: That's excellent. So as a sarcoma guy where I'm used to everything just clumped together, more specific is always good.
Emrullah Yilmaz, MD, PhD: Yeah.
Dale Shepard, MD, PhD: That's a good thing. I guess guidelines kind of help in two settings. Sometimes they help physicians know what to do and how to guide patient care. Have there been insurance barriers in the past with getting some of these therapies covered that these guidelines might help with?
Emrullah Yilmaz, MD, PhD: Correct. So, I think that is one other thing that might help the physicians to refer to these guidelines as well, if there's any challenge to get these immunotherapy as approved for the right indication when they try to get the patients access to these medications. So that might help to get access to the patients as well.
Dale Shepard, MD, PhD: Yeah. What are the biggest questions that remain? So, it sounds like you've made good progress in sort of a subset of the big picture head and neck. What are the big unanswered questions that might be for the next set of guidelines?
Emrullah Yilmaz, MD, PhD: So one of the things that are emerging, and again, rather than the guideline, especially from the research perspective that are going on in the immunotherapy is, so that is why we've wanted to focus just the recurring metastatic for this guideline is there are a lot of research going on in immunotherapy in the creative intense setting, especially with the chemo radiation and immunotherapy and after the surgery with the chemo radiation. So that's why there are a lot of unanswered questions from that part. So that's why there is no indication right now to use immunotherapy in the creative intense setting. So that's why this guideline focuses more on the recurring metastatic setting. So that's why that is one of the unanswered questions. And if there is more that comes up in the future in the creative intense setting, that might be the next guideline that comes up in immunotherapy for head and neck cancers.
And the other thing is if the patients have any progression beyond immunotherapy, there are a lot of trials going on how to overcome the resistance to immunotherapy with different combination strategies. And if some novel strategies and some novel treatments come up with that. So, this guideline might be updated in the future and ASCO is coming up with these updates every few years if there are new indications that come up and new findings that comes up with the treatments.
Dale Shepard, MD, PhD: Within the head and neck community, are these earlier phase trials, are they relatively easy to do? I know in some tumor types it's difficult because a patient might see a surgeon first and they may go ahead and have surgery and not sort of think about those trials that might be in play. So, has it been relatively easy to answer those questions regarding head and neck cancers?
Emrullah Yilmaz, MD, PhD: In head and neck cancers it has its own challenges because we have to get access to the patient and get the patients on a clinical trial as early as it is possible. If the cancers start to progress, then we might have also a short window to get the patients on a clinical trial as well. So that's one of the challenges. But at the same time, there are a lot of novel strategies that are coming up as well. So that's why there's still room for improvement for these treatments. So that's why, especially for more targeted approaches. So those are the things that might be coming up before these patients.
Dale Shepard, MD, PhD: And I guess continuing to think forward, mostly this, as you said, is focused on checkpoint inhibitors, but there's an entire next wave of immunotherapies in the future. Is there anything in your head and neck that looks particularly promising that your kind of hoping, looking longingly at the trials to hope they work?
Emrullah Yilmaz, MD, PhD: Yeah. There are, for example, vaccine strategies coming up, HPV positive cancers are its own group. For example, HPV targeted therapies are emerging right now. So that is its own group and there are some really exciting therapeutics that are coming up in that group. And there are some other checkpoints other than PD-L1 that are emerging. So, there are definitely some other treatments that are potentially effective in the future and so on.
Dale Shepard, MD, PhD: Excellent. Well, it looks like you guys have synthesized a lot of data and come up with some good guidelines and should help patients and looks like there's promise for the future. So, appreciate your insights today.
Emrullah Yilmaz, MD, PhD: Yeah, thank you so much.
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