Nabil Saba, M.D., FACP, an oncologist and the director of head and neck oncology at Winship Cancer Institute of Emory University in Atlanta, Georgia, talks about how immunotherapy may be an effective treatment for those with head and neck cancers that spreads or comes back.
Interview conducted by Ivanhoe Broadcast News in March 2017.
Head and neck cancer this is something that doctors are seeing on the increase, can you tell me a little bit about that?
Dr. Saba: Yes, head and neck cancer is a group of different diseases. They’re a heterogeneous group of diseases. The heterogeneity comes from the characteristics of where the cancer is, where the cancer is located. Over the years we have learned that the heterogeneity also comes from the causes of this head and neck cancer. The vast majority of head and neck cancers that we’re used to see or have used to see are linked to risk factors such as, alcohol, tobacco traditionally but over the last couple of decades HPV which stands for the human papilloma virus has been recognized as one of the major cause of oralpharynx cancer. Which is cancer really of what we call base of tongue, which is the part of the tongue that when we examine patients by just a simple examination as well as tonsil cancer. Both of these cancers were thought to be increasing first in Caucasian men but we’re learning now more and more that this is not just a disease restricting to Caucasian men. That other portions of the population also may have increase in the HPV related cancers. Now the interesting thing about HPV related cancers is that patients with this disease seem to do better than patients each additional non HPV non-related cancer. They seem to have a better survival. The biology of the disease is different. The behavior of the disease is different. Patients seem to be younger, seem to be healthier and seem to be more curable. So over the years we have basically tried to see how to best apply what we already know works for the HPV negative group and apply it for the HPV positive group. Keeping in mind that for the HPV positive group we don’t need to be necessarily as aggressive in the treatment because these cancers do better. We’ve been trying to de-intensify the therapy and de-intensification comes through either reducing the dose of radiation or relying more on surgery as the main option for treatment for early stage disease. We can also rely on decreasing or changing the type of chemotherapy that we give. There are different ways that we’re currently struggling to basically come to a consensus as far as how best to treat the HPV positive disease. But regardless of this effort, these patients who have these tumors basically have a better chance of surviving and be cured of their disease.
What is the standard of treatment? Is it surgery or a combination of a couple of things or is it patient dependent?
Dr. Saba: The standard of treatment has moved over the years. Traditionally what we have done and I’m going to focus here just on what we call the oralpharynx cancer and oral because it is one of the most common subtypes of head and neck cancer. Also really focusing on the base of tongue and tonsil cancers. Traditionally in the very old days we used to rely on surgery but over the last twenty years or so we have relied really on the combination of radiation and chemotherapy. We have used this combination very effectively in treating these patients. To come to realize that there is a price when we combine radiation and chemotherapy and this price is affecting the overall health of the patients so there are complications that these patients have. The complications can range from the acute side effects that the treatment may cause including severe mouth pain and inflammation; we call that mucositis. We use a drug called cisplatin which is still very much in use and this drug can cause kidney failure. It can affect hearing so it can cause hearing loss in a certain number of patients and can cause also nerve damage, so neuropathy. Those side effects may linger over the long term patients may have some dry mouth as well in about twenty five percent of patients may continue having dry mouth.
Talk to me a little bit about immunotherapy and how this plays a part in treatment. Is it something that is being used at this point?
Dr. Saba: Yes. I want to continue a little bit about the oralpharynx cancer. The combination of radiation and chemo basically has been used over the last twenty years. Lately to bring it back to what we were starting talking about, which is basically the de-intensification. Because we have more and more HPV positive disease we’re trying nowadays to essentially try to de-intensify the treatment. This is where we basically move to surgical resection, lowering the dose of radiation, relying more on chemotherapy as a modality. Immune therapy is a complete game changer in the way we look at head and neck cancer. As a matter of fact different types of cancers but I’m going to focus mostly on head and neck cancer.
How is it a game changer?
Dr. Saba: The traditional treatment for head and neck cancer patients is really toxic and exhaustive and leads to side effects that are very significant. For the first time in a long time we have evidence that a treatment may actually help improve the outcome for patients with head and neck cancer while it is preserving their quality of life. They are actually enjoying their life and not having to endure the very hard toxicities that chemotherapy and radiation traditionally have caused for these patients.
Can you explain immune therapy and how it works for head and neck cancer?
Dr. Saba: Head and neck cancer is one of the cancers that does cause immunosuppression. The tumor cells basically create an environment around them where the immune system is suppressed. This is not very strange to the human body because our normal cells basically always create an environment around them to avoid the attack from the immune system and to protect themselves from the immune system. Cancer cells have learned this process and basically have learned how to create an environmental immunosuppression. It seems that environmental immunosuppression is more pronounced in head and neck cancer patients and so on that ground it makes a lot of sense to use immune therapy. In anticancer treatment that would actually bypass this suppression and leads to the immune system actually being reactivated to go in and attack these cancer cells. On the other hand within the same tumor type or within the same location of cancer we have a virus which is the HPV that essentially leads to the occurrence of HPV related head and neck cancer which is a subtype of head and neck cancer. The best way our body fends against viruses is really by having a robust immune system. On one hand you have the tumor that basically suppresses the immune system and that does not have to do necessarily with the virus but on the other hand you have a virus that’s causing the cancer. On both counts immune therapy basically stands to make a difference in head and neck cancer as it is already is doing.
Can you talk to me about how the drug is created?
Dr. Saba: Sure. When you want to boost the patient’s immune system you don’t want the immune system to start attacking every normal cell. What the current drugs are focusing on is a result of years of research that looked at what are the signals that the cancer cells send to the immune system to avoid the attack from the immune system. One of these signals is we call it the PD1, PDL1 axess. There are many other systems but this is what the focus seems to be on mostly at least in head and neck cancer. What these drugs do basically is they come in and block the PD1 Or PDL1 receptor. By doing that this bondage if you like or this unhealthy relation between the tumor cell on one hand and its upset of immune cells which is the lymphocytes basically is broken by these drugs. Now that this messaging if you like is broken the lymphocytes now recognize the tumor cells as enemy and they basically start fending against the cancer.
How effective is this treatment. Are you starting a study?
Dr. Saba: Yes. There are several studies and at least a couple two or three large studies in head and neck cancer that have shown significant promise. The most prominent one currently and the largest one that has been reported so far is a study called checkmate one four one which is a study that compared the traditional chemotherapy drugs that we use for patients who have advanced cancer. Those are patients who don’t have curable cancers. We talked earlier about the HPV positive and how those are beyond this point. Those are patients who basically don‘t have many options. They have a short survival time usually an average survival time of about eleven months or so with a traditional chemotherapy. What this trial did is it took about three hundred and some patients and randomized them to one of the PD1 inhibitors which is called Nivolumab on one hand. Two thirds of the patients received that drug and the one third received the standard chemotherapy which is basically what we give these patients with advanced head and neck cancer. Those are different types of chemotherapy because we really did not have a good understanding as far as what is the best one. What ended up happening is that the group that received the Nivolumab which is immune therapy survived, had a chance of survival which was double that of the group that received the traditional chemotherapy at twelve months or at one year. From the time they started the treatment to and when we looked at the results at one year the survival patients who got the immunotherapy was twice. Not only that but when more analysis was done it seemed that these patients actually had a preservation of their quality of life. Whereas patients who went on the chemotherapy had significant deterioration which is what we expect because we’ve treated patients with chemotherapy over many years and this is not something different from what we expected. The new information which is very significant I think is that the group that got the Nivolumab or the immune therapy had a preservation of their quality of life. For the first time we have seen a drug that has actually improved the survival of patients with head and neck cancer. These drugs were the first drugs to be approved since 2006 by the FDA. It basically took us a decade since the last drug was FDA approved for treating advanced head and neck cancer to get to a point where we have newer drugs now that seem to be working but also seem to be preserving the quality of life for patients.
I wanted to ask you about your patient Leonard, can you speak to his case a little bit?
Dr. Saba: Yes, absolutely. Leonard is a patient who specifically has HPV positive head and neck cancer. When he came in because of his HPV positive disease we were very optimistic that he would be cured from his disease. He came in with a disease that was restricted to the neck and the neck lymph nodes. We treated him actually on a previous clinical trial that basically was aiming to de-intensify the therapy for HPV positive disease. He ended up being on the treatment that was not the de-intensified treatment so he got the full treatment with cisplatin and radiation therapy which is the traditional treatment that we have been giving patients with head and neck cancer. Treatment is fairly hard on patients. By the end of the treatment most patients are very fatigued, most patients have limited ability to swallow liquid and solids and they rely on a feeding tube. The unfortunate thing with Leonard’s situation is that soon after we completed the treatment, within the first year his cancer showed up again. The cancer at that time showed up in his lungs mostly. At that time we did not have immune therapy approved and we did not have trial supporting immune therapy. We ended up giving him treatment with a drug called cetuximab which has been a drug approved by the FDA since 2006 for treatment of head and neck cancer. In combination with other chemotherapy drugs as well and he did struggle with that because he did have significant skin toxicity from cetuximab and I think his quality of life was not the greatest when he was on this combination of treatment. He did respond initially to some to the treatment but then his disease stopped responding and the lung lesions continued to increase in size. He had a very good response to the treatment, to a point where we could not see any lung lesions on the scan. Not only that, his quality of life has been maintained so besides having to come in to the infusion center and having an infusion sitting there for an hour once every three weeks he appears to be having a very good quality of life; appears to be having a normal life. Goes on hikes, and we try to find out if he has any symptoms every time he comes to the clinic but he seems to be in a different place right now. With these drugs I think one we were using chemotherapy in the past I think we were asking the question who can receive chemotherapy because not every patient can withstand the toxicity of chemotherapy. If you have organ damage, if you’re elderly, if you have other medical problems chemotherapy may not be the right fit for you. Whereas nowadays with these drugs with immune therapy I think the approach is slightly different and even though we are still learning about who can and cannot receive immune therapy I think the mindset is, is there really a reason for not giving immune therapy to a patient? That is completely different from the mind approach that we had when we were deciding who should and should not get chemotherapy.
I just want to make sure that there’s no sign of cancer right now.
Dr. Saba: What he has appears to be related to his difficulty swallowing. Some of the oral contents may go in the wrong direction. There is a little bit of what appears to be inflammation in the lung but there is no clear sign of cancer and this has been going on again for more than twelve months.
What is the prognosis for someone that’s diagnosed at Stage 4, at what point can you call it a cure, what is the likelihood of a recurrence?
Dr. Saba: This is an excellent question. When we talk about Stage 4 head and neck cancer we think of it as an incurable cancer. Sometimes when the cancer comes back in the neck there are possibilities of being able to cure this cancer if the patient is still a candidate for surgery, or some patients may still be candidates for re-exposing them to radiation. Those are a few patients so those are the few exceptions of being able to get cured from recurring advanced cancer. Once you have distant metastasis, in other words once the cancer is outside the neck we tend to think of it as incurable cancer and so the question is, is it possible to cure these cancers with newer drugs, with immune therapy. This is our hope. But we cannot say that for now. Even though Leonard continues to be doing very well with the treatment he’s on and we hope that he obviously continues to do extremely well. We still don’t have enough information to tell us how long this will continue. Whether at some point in time it makes sense to stop and watch or whether we should continue indefinitely- until we stop seeing responses to these drugs.
Is there anything I didn’t ask you that you want to make sure people know about this treatment or head and neck cancers?
Dr. Saba: We live now in a new era in oncology and in head and neck cancer and I think these trials that have resulted in very good outcome have really opened the door for treating patients in a very different way. But have also opened the door to ask the question of how immunotherapy can help also in the earlier stage cancers. We talked about the toxicity of chemotherapy, the toxicity of radiation, can we include these drugs in earlier stage cancers and we’re already looking in to these questions. There are already trials that are basically asking these questions and investigating these questions. We hope that the future will carry better outcome for these patients as well when we use immune therapy.
END OF INTERVIEW
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