Head and Neck Cancer and Immunotherapy

October 7, 2021, 5:00 pm -
5:30 pm
New treatments to preserve quality of life

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Session Description

Immunotherapy offers exciting new treatment options for patients with cancers of the mouth, throat, voice box, sinuses, nose, and salivary glands—especially those with HPV-positive cancers. Standard treatments have potentially devastating side effects for speaking, swallowing, and expression, so new options which preserve these functions are vital. Join Dr. Nabil Saba, director of the head and neck oncology program at Winship Cancer Institute at Emory University, in a Q&A discussion about the use of new checkpoint inhibitors and other immunotherapies in head and neck cancer. Ask him your questions about clinical trials, treatment regimens, side effects, and other topics.


Session Transcript

Tamron Hall: Welcome back. It’s my pleasure now to introduce you to Dr. Saba, who is here to fill us in on the latest advances in immunotherapy for head and neck cancer. Dr. Saba is a professor and vice chair for quality and safety at the Emory University Department of Hematology and Medical Oncology. He’s the director of the Head and Neck Oncology Program and leads the Head and Neck Working Group at Winship Cancer Institute at Emory University. I’ll now turn it over to Dr. Saba and Dr. Brodsky as we delve into immunotherapy for head and neck cancer.

Dr. Nabil Saba: Good day, everyone, my name is Dr. Nabil Saba from the Winship Cancer Institute at Emory University. It’s a great pleasure to be here and welcome to everyone who’s joining the CRI virtual meeting. Today, we’re going to talk about head and neck cancer.

So head and neck cancer, in my view, is the poster child for immunotherapy. And this is a cancer that comprises several diseases, not just one disease. You have cancer in the perinatal sinuses, as you can see here. Cancer in the oral pharynx, which is the tonsil base of tongue cancer in the oral cavity, and these cancers are caused by different risk factors. The most prominent, most lately over the past 20 years has been the infection by the human papillomavirus, or HPV, and that has resulted in a significant increase in the incidence of oropharynx cancer over the last 20 years, and we continue to see an increase in these types of cancers, and so I think we have a great opportunity here to tackle a question of viruses mediated cancers and see how immunotherapy and the immune system is able to be harnessed to basically treat the cancer in these virus mediated tumors. On the other hand, we have non-virus mediated tumors, which are linked to environmental exposures such as tobacco, alcohol, and those have always existed in head and neck cancer, and so over the last several years, we have focused on trying to intensify therapy because HPV related disease usually does better than HPV unrelated disease. And so historically, the treatment has been radiation surgery, chemotherapy. And most recently, while all this has happening, immunotherapy has come to the scene and has become a fourth modality. This has been a very welcomed modality in head and neck cancer, given the fact that it is much better tolerated than the traditional treatment of surgery, radiation and chemotherapy. Head and neck cancer patients suffer from their disease, but they also suffer from the treatment that is fairly rigorous on them and results in significant side effects.

So we’ve talked about HPV. HPV stands for human papilloma virus, and we think that immunotherapy efforts would benefit greatly HPV related cancer, those immunotherapy efforts focus on targeting the PD one PD-L1 access to treat HPV related cancers, but also more recently focus on very exciting research in terms of vaccine development for treatment and targeting HPV related proteins. We know that the immune cells are there, they’re waiting to attack. We’ve studied this in patients with HPV related head and neck cancer, and we find that these immune cells are already in the lymph nodes. So our immune cells that are very specific to the HPV virus and they’re ready to attack. So we just need to know how to harness this immune system to be able to attack the disease.

So in the first place, the question is how do these cancer cells escape from the immune system? You’ve probably heard some of this earlier in this symposium. What we would what I would abbreviate this as is that cancer cells like normal cells express certain receptors that allow the immune system to avoid attacking these cells, and so this includes the PD one PD-L1 axis you have here an immune cell that is trying to attack a cancer cell. And what happens is basically the attack is dependent on essentially the PD one PD-L1 axis not being activated. So when we add a drug that inhibits the PD one PD-L1, we block this pathway and then we allow the cancer, the immune cell to basically attack the cancer cell, and this will result in elimination of the cancer cell. So this is a simple principle that resulted in approval of several drugs in the treatment of head and neck cancer, including PD one inhibitors. Mostly, however, this is just scratching the surface of how much we can harness the immune system in treating head and neck cancer and other cancers.

You heard about patients’ examples, and Ricky is a patient with head and neck cancer who was treated by one of my colleagues and who benefited greatly from immunotherapy. This was particularly important because he’s a singer in a band. I can give you examples of other patients who basically benefited greatly from immunotherapy patients who came in with advanced disease, metastatic disease, and who five years ago, I would have never thought they would be cured from their cancer. However, five years later, we don’t have evidence of cancer in their in their system, and basically, they’re leading a very good quality of life post treatment of their cancer.

So what does the future hold? I think the future is very promising for head and neck cancer and for immunotherapy in head and neck cancer for the reasons I mentioned earlier. So currently, we do have agents or drugs approved for treatment of metastatic disease, but currently these agents are being moved to implementation and treatment of definitive, definitive or early stage cancer, earlier stage cancer. These are being combined currently with radiation therapy being added to surgery, sometimes being used before surgical resection, and I am very, very hopeful that these treatments in the next decade or so will change completely the standard of care and the management of head and neck cancer. That’s all I have, and I’m happy to answer any questions.

Arthur Brodsky: Thank you, Dr. Saba, for that, for sharing that information with us. So it’s great to hear how much of an impact immunotherapy has already made, especially, you know, I guess most of your examples were about advanced head and neck cancer. So overall, obviously it has begun to transform immunotherapy has begun to transform management of head and neck cancer. Do you still feel that it’s in its beginning stages, though?

Dr. Nabil Saba: Yes, I do. I do believe that it is in the beginning stages, even though we have had very, very encouraging results. I mean, we went from not being able to cure a patient with a disease that essentially has a very high mortality in the metastatic setting to being able to observe. Patients have maintained responses over a much longer period of time, and that in itself is a major victory. However, I do believe that we’re still scratching the surface of what we can do. HPV is a great example, and I think there will be one day where I predict we will be eradicating, and I mean, the word eradicating HPV related head and neck cancer, whether it be through extensive vaccination against HPV or whether through improvement in our immunotherapeutic approaches to treat HPV related cancer, I think we have a great opportunity to be able to eradicate a disease. This will not happen tomorrow, maybe not in a decade, but we have the potential to achieve that goal.

Arthur Brodsky: I agree with you that I hopefully we are well on our way. The science is strong and it seems to be that we’re going in the right direction, and so I was wondering if you could explain why go into a little bit more detail about why immunotherapy works so well, you know, for head and neck cancer in general, but especially in patients who have tumors that are infected by the human papillomavirus or HPV. And then by the same token, could these immunotherapies also work in other cancers that that are commonly infected by HPV, such as anal cancer or other genital cancers? Cervical cancer too?

Dr. Nabil Saba: Yes, so this is basically entering the topic of virally mediated cancers and as you as your indicated, HPV is one example of these cancers, and what happens is, you know, the cancer cells are able to escape from the immune system for the for the reasons, for the reasons we mentioned, and so you have a virally mediated tumor on one hand that essentially is able to escape the immune system, but also in head and neck cancer. We have the non-virally mediated tumors, which are linked through increased genetic mutations that lead to also increase ability of these cells to escape from the immune system. So you have the two models in one disease, and I think that that is a big advantage. Also in in in getting to an answer as far as how immunotherapy works. We still don’t know the in great details how the virus essentially leads to these cells escaping the immune system, but certainly what we’re observing is that when we target these tumors with immunotherapy, they tend to respond very well, specifically the HPV related ones.

Arthur Brodsky: That’s promising to hear, and one of our attendees is curious about where immunotherapy is now in the course of treatment. Is it standard of care for patients or would they have to undergo another treatment first? And this is with respect to HPV related head and neck cancer?

Dr. Nabil Saba: Yes. So we have two drugs that are approved for recurrent metastatic HPV related cancer, and those are approved also for HPV unrelated cancer, because the studies that were done essentially included both HPV positive and HPV negative cancers. Those are just recurrent metastatic patients for the time being. However, there is a lot of efforts ongoing to basically try to introduce these immunotherapeutic agents into definitive treatment setting for patients who do not have metastatic disease. For patients who are seeking to get cured in the definitive setting, whether it’s early stage HPV positive or HPV negative disease, and we’re not saying we will not encounter roadblocks. I think one of the largest one of the large trials recently, unfortunately, was negative in terms of adding a PD-L1 inhibitor. But we’re trying to understand exactly what is the best way to sequence these drugs with radiation to sequence these drugs with surgery. Because these modalities, the radiation or the surgery, as I mentioned earlier, they remove the cancer, but they also remove the immune cells from the tumor microenvironment, and so when you’re actually killing the immune cells, you are actually killing the force that is supposed to fight these cancers through the immune system, and so the question is how best to introduce these agents? I think there is a lot of enthusiasm about introducing these drugs, perhaps first before going to surgery or first before going to radiation to try to harness an immune response against these tumors and then potentially go to the traditional treatments if we need to. Because as I mentioned research at Emory University recently, we looked at the presence of these immune cells that are very specific to the HPV virus, whether they are B cells or T cells, and those T cells that are specifically directed to the HPV virus are sitting there waiting for a signal to attack, and so I think and we found that in large proportions of HPV related head and neck cancers and these cells are present in large quantities. In other words, you know, we have not been able yet to harness these immune cells in an effective way to actually attack these tumors, which is why I’m somewhat optimistic that the future will basically be more promising for these patients.

Arthur Brodsky: That was interesting, you brought up several important points, I thought, especially, you know, how are traditional treatments chemotherapy? Radiation surgery can help augment immunotherapy, but as you mentioned, in some situations, it might be counterproductive. So there’s definitely still a lot of questions out and studies still being done to determine the optimal ways to combine these therapies, and obviously, a lot of those are all of those questions really are being the answers are being sought in clinical trials. So to that end, could you discuss some of the promising clinical trials for head and neck cancer at the moment?

Dr. Nabil Saba: Yeah. Arthur, I would add also that it depends on the dose also of the radiation. For example, a small dose of radiation could actually be an immune stimulating, whereas a big dose of radiation could do the exact opposite. So we still need to understand how the radiation exactly can be harnessed to actually help the immune system attack. As far as the clinical trials, we have very exciting efforts in the realm of HPV related cancer and head and neck cancer. We have combination trials. We have drugs that have been used in head and neck cancer and have been approved over the last decade or so. So there is a combination of these drugs. A drug called cetuximab, which targets EGFR, which is epithelial growth factor receptor, has been proven to be effective in head neck cancer. And now we have studies that are combining cetuximab with these immunotherapeutic drugs and are showing some promise specifically in the HPV related and I’m here talking metastatic disease in the HPV related cancer cancers. There is a very exciting effort looking at vaccines and here I’m talking about tumor vaccines, but also vaccines that are targeted towards the HPV related proteins. We all know the COVID vaccine with all. Many of us have taken the COVID vaccine. There is an equivalent RNA vaccine against HPV, and some of you may have heard that there’s an interest in moving these RNA vaccines into the cancer world, and so there is a large trial now that’s an international study that is looking at an RNA vaccine very similar to the COVID vaccine, and if it has the same success as a vaccine in terms of, you know, promoting an immune response against HPV related proteins, I think this may hold promise. Of course, the trial is still early in its accrual as far as the definitive treatment setting. We’re still waiting for some studies to mature. I’ve talked about one trial, which was the javelin trial, unfortunately, was a negative study. And here it may be because the immunotherapeutic drug was added on top of radiation and chemotherapy, and maybe that’s not the right way to do it, and so there are there’s another trial along those same lines that we’re waiting to see the results of, but there are also efforts. I mentioned one trial that we are pushing or that is accruing currently at through the ECoG Eastern Cooperative Oncology Group setting that is adding a PD one inhibitor after the radiation and chemotherapy is over. In other words, patients get treated first with the definitive treatment. Those are patients with locally advanced disease, HPV related disease, and then they get the immunotherapy drug maintenance after the after the definitive therapy. There is some precedent in lung cancer that this approach may be actually beneficial for patients, so we are hopeful that this may lead to positive results. There are other trials looking at introducing these drugs before surgery because we do have the advantage in head and neck cancer also to look at what happens before and after these drugs, since many of our patients actually have to undergo still surgical resection, and talking about patients who have tongue cancer, who have oral cavity cancer, but also some patients who have HPV related cancer, who can who are sometimes treated with oral robotic surgery. Those patients currently are getting accrued to clinical trials that are looking at preoperative use of immunotherapy before surgical resection and those trials. We stand to learn a lot from these studies, and we’re already learning a lot from them in terms of how do these drugs actually alter the tumor microenvironment, specifically the immune microenvironment of the tumor? And that will teach us a lot, I think, in terms of what happens exactly when we use these drugs.

Arthur Brodsky: Interesting, it’s great to hear that all these different options are being explored, and, you know, I guess it kind of makes sense with how complex the immune system is, especially compared to chemotherapy and radiation. Immunotherapy is a much subtler and more non-linear tool, I guess, so it makes sense that there’s still a lot we have to learn about it. So several of our audience members are interested in the length of time that one should take immunotherapy. So there’s a several part question. But generally, how long are patients treated with immunotherapy, and does the length of time vary based upon the effectiveness? Then to get a little bit more specific about it? One of our attendees mentions they have stage four head and neck cancer and have been on checkpoint, have been on a checkpoint inhibitor for five years and are currently no evidence of disease, thankfully, but they ask what happens if they stop treatment and if the tumors come back, can they restart it?

Dr. Nabil Saba: Yes, those are all excellent questions, and we struggle with these questions, Arthur, on a daily basis in our clinic, the clinical trials that were designed to test these agents basically use them for a year or two years. And then most of these trials stopped. There are some trials that allowed the continuation of these treatments. I can give you an example of one of my patients who got treated for two years on the very first trial that led to the approval of pembrolizumab in the treatment of recurrent metastatic head and neck cancer, and after two years, he had the option of continuing or stopping, and he chose to stop because this disease has disappeared, as is one of the one of the audience members is mentioning here, and then it has been now about four years since he stopped and the cancer never came back. So he had HPV related cancer. He was treated initially with radiation and chemo and then had metastatic disease to the lungs. So that is one example. However, one example does not mean everyone will have that same experience. I think I tend to, after two years, have a discussion with my patients, especially those patients where I don’t see really any evidence of disease and who have had a deep and lasting response to immunotherapy. There is a difference between a patient, for example, that has a deep response and lasting response and the patient where it takes time to achieve that complete remission. Sometimes the immune system does not really attack in a very effective way, and so you see these stable disease situations that ultimately lead to a partial remission and these settings, I would be less encouraged to stop. But in a patient who has complete remission, I think the question is very valid and I usually try to ask this at two years. Can the cancer come back after two years? Yes. I think that is the struggle that patients and physicians have to go through when they have these discussions, and it is not easy to do these trials. I think there was an attempt to do such a trial looking at duration of immunotherapy, whether six months or a year would be the way to go. And I don’t think the effort led to moving on with this with this research, simply because there is so much heterogeneity in each situation. Each patient is different, each disease situation is different. You cannot really implement this to multiple diseases because what could happen in head and neck cancer may not be exactly what happens in lung cancer, for example, or what happens in melanoma, and so I think this is a question we’ll continue to struggle with, but I think there are certainly patients where I would consider having a discussion about possibly trying to stop and see what happens.

Arthur Brodsky: Gotcha. And so on a similar note, you know, we were just talking about you were just talking about somebody who was on immunotherapy and who had responded to it and their long term, you know what they should consider for long term receiving the treatment. Another patient in the audience mentions that they were diagnosed with squamous cancer of the tongue five years ago, and they had surgery that went well and they’re on surveillance right now. So even though they seem to be cancer free at this point, they’re wondering if they should still consider immunotherapy to prevent recurrence.

Dr. Nabil Saba: Yeah, I mean, I think five years out, first of all, congratulations on being disease free for five years. This is great in medical oncology terms. We would call this a cure. I do not recommend going on immunotherapy right now. I think if in five years the cancer has not shown up, it could be that your own immune system has basically taken care of whatever residual cancer cells existed, and let’s remember that even though the topic of immunotherapy is very exciting, these drugs are not completely devoid of side effects. You know, there are side effects of these for these agents, so I would not recommend adding immunotherapy five years after a remission. Also, for another simple reason is that you have no idea what it is doing. You know, is it really helping to target cancer cells? You have no, there’s no way to measure success. And then the question comes for how long and what to use. All these are, I think, valid questions. There are trials, by the way, that are looking at that. But those are trials that are looking at introducing these drugs much earlier after definitive therapy and for patients who have very high risk of recurrence. In other words, patients who have relatively high stage disease that’s not metastatic treated with radiation and chemo, and then they go on this immunotherapy drugs or, for example, patients who have metastatic disease. And sometimes we do ask our surgeons to remove these metastatic lesions because they are very few in numbers. Let’s say one metastatic lung lesion or two metastatic lung lesions. We call that metastatic disease, and those patients appear to have a different prognosis than patients who have multiple metastatic lesions, and so there is a rationale here for maybe trying to target this with local therapy, and the question in the setting is would adding immunotherapy early on after this process help? There are trials that have that are looking into this question.

Arthur Brodsky: Gotcha, and for patients who might be interested in a clinical trial, where might they be able to go about finding if there’s if there’s a clinical trial that might be suitable for them?

Dr. Nabil Saba: So I think a great resource is, I’m sure you know, and your audience may know is the clinicaltrials.gov, and that’s the website where you can search the open clinical trials currently in the United States. Any trial that is open that this therapeutic has to be registered through that website, and so depending on which search items you enter head and neck cancer metastatic, you can see which trials are opened. You can see where the trials are opened, which cities, and you can see whether the trial is actually active or completed accrual, and so I think that would be probably the most reliable resource. I would add that head and neck cancer is not a very common cancer in the big scheme of things. We’re not talking about a disease that is as common as prostate, lung or breast cancer. We’re talking also about a disease that is complex. The treatment itself is very complicated. I would urge patients to seek advice in high volume centers and centers that are specifically focused and known to be able to focus on treating this disease because also the treatment of this disease is a multidisciplinary approach. I cannot. I can never treat a head and neck cancer-based patient by myself. I’m a medical oncologist that does not speak to my capacity as a medical oncologist, but I’m not a surgeon, I’m not a radiation therapist, and those colleagues of mine are very, very much needed. Together with medical oncology to be actually able to reach an effective treatment and good results for patients with head and neck cancer.

Arthur Brodsky: Those are very important points that we are. This is still the science is advancing every day, and the more minds that you can get together, the more cures will be able to get to. So one of our audience members asked about after treatment again, how long are patients typically followed after immunotherapy treatment? And are there any survivorship programs for four cancer patients that they should be aware of?

Dr. Nabil Saba: Yes. So it depends on which stage of disease are we talking about. So I think if there is immunotherapy use for recurrent disease, which is the current approval status for immunotherapy and there is a very good response to immunotherapy, I continue to follow these patients and I currently I would not stop following just because we still need time to get to a definition of what have we cured these patients? We are very encouraged by the fact that we have long term remissions in this disease, but let’s remember these drugs were approved in 2016. We’re not talking about, you know, we haven’t been yet in this in this field for a decade or more. So we need to really be vigilant about that for patients who basically don’t have evidence of disease after definitive treatment. I think the way we approach things is to do a pet scan at three months and CT scan of the neck, and then if that’s negative, go to every six months for two times and then after that once a year for five four until the end of the fifth year, and then we would stop after that.

Arthur Brodsky: Thank you for that information. So as far as prevention, if someone has HPV, which would mean that they are at higher risk of developing head and neck cancer. Are there any ways that they could or any actions or behaviors they could take to help minimize their chances of cancer developing, and I guess even in that regard, whether or not they have HPV?

Dr. Nabil Saba: Ok, that’s a very important question. First of all, let me let me stress the fact that many, many of us have HPV. If you walk on the street, more than 90 percent of people probably had or have HPV in their oral cavity or oropharynx. Very small fraction of these individuals will end up developing cancer. It is not clear why is it related to reinfection? Is it related to the immune system inability to actually fend off the virus? Those are all good questions. What I would say is the projections is that over the next 10 to 20 years, the HPV related oral cancer will increase dramatically and in 10 to 20 years, it will affect mostly patients at the age of 65 or older, which means that currently these people are not getting vaccinated. Whereas if you look at the incidence in patients who are 10 to 20 years from now will be in their 40s, that is supposed to plateau, and so, you know, the CDC’s recommendation is to vaccinate for a certain age, but I think we don’t have time too much time to talk about that, but I think there are those who are proponents of vaccinating people for HPV related cancer regardless of their current age. Certainly, if you’re a young person, I think I am in favor of promoting vaccination, given the projections of how this this will pan out in the next 10 20 years. But that requires a whole different session and discussion. I think.

Arthur Brodsky: Absolutely agree, and so to that end, would the HPV vaccine be something that, you know, I guess, you know, before you have cancer, it seems like it would definitely be something that’s better late than never. But what about somebody who already has cancer? What if they haven’t already been vaccinated against HPV with the vaccine potentially help them?

Dr. Nabil Saba: So there’s no evidence that vaccination against HPV in terms of the vaccine for prevention actually helps in this situation. However, the trials I’m referring to for the audience to understand those are tumor vaccines. They’re not really the same as the approved FDA vaccination against the virus to get the infection. Those are tumor related vaccines, so you’re actually vaccinating against the tumor. This is a different topic, and so to answer your question, Arthur, no, I would not recommend vaccinating a patient who already has HPV related head and neck cancer because there’s no evidence that this will help, and I’m drawing this conclusion also from studies that were done in cervical cancer.

Arthur Brodsky: Ok, that makes sense, and so now as we wrap up, how is immunotherapy changed your outlook on cancer care? And do you think that immunotherapy will one day become broadly available as a first line treatment for all types of cancer?

Dr. Nabil Saba: As a head and neck cancer expert, I think immunotherapy has completely changed my world and the world of cancer patients. We went from a disease where we don’t have many options. This is not a disease where we have a list of large numbers of targeted agents waiting for it to be used. We don’t have many targeted agents. We have just cetuximab that has been approved over the last 20 years for treatment of metastatic disease, and so, as I said, immunotherapy and head neck cancer stand to make a big, big difference in this disease, and I think and I think I’m optimistic that there will be a day when we will see this as the first line treatment for patients. Certainly, it is currently the first line for recurrent metastatic disease. It is included for every patient who has metastatic head. Neck cancer should be receiving one way or another immunotherapy, but I’m talking about patients who have not developed metastatic disease, who are curable patients, and I think immunotherapy will be incorporated in some way, shape or form for treatment of this of these patients.

Arthur Brodsky: Yes, very happy to hear about your optimism, and hopefully, as these studies bear out and physicians and scientists such as yourself, their work continues to advance. Hopefully, we can get closer to cures for more patients and more settings as well. So that’s all the time we have. I want to thank you very much, Dr. Saba, for sharing all that information about immunotherapy for head and neck cancer, and I would just like and also thank our audience. You had such great questions and unfortunately, we weren’t able to get to them all, but we will have a post in the future that hopefully Dr. Saba can address any that are outstanding. Thank you, Dr. Saba, for taking the time with us today.

Dr. Nabil Saba: I want to thank you, Arthur, for a great discussion and very fruitful, very fruitful session. So thank you very much. It was pleasurable.

Arthur Brodsky: Take care.


Nabil F. Saba, M.D., FACP

Winship Cancer Institute at Emory University

Dr. Nabil Saba is a professor and vice chair for quality and safety at Emory University’s department of hematology and medical oncology and holds a joint appointment as a professor of otolaryngology at Emory University School of Medicine. He serves as the director of the head and neck oncology program and leads the head and neck working group at Winship Cancer Institute at Emory University. He is a recognized expert in head and neck cancer immunotherapy, focusing his work on translational research and the study and development of novel therapeutics in head and neck and esophageal cancer. Dr. Saba leads several clinical trials with a focus on biomarker endpoints and has received NIH funding to examine novel genomic approaches for diagnosing HPV positive oropharyngeal cancers. He has chaired the Head and Neck Cancer NCI Steering Committee’s Rare Tumors Task Forces. Dr. Saba is an appointed member of the ASCO Clinical Guidelines Committee as well as the ASCO Head and Neck Guideline Advisory Group.

On-Demand Now Available

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