In this podcast, Dr. Ezra Cohen discusses some of the research on head and neck cancers presented at ASCO’s 2015 Annual Meeting.
ASCO: You're listening to a podcast from Cancer.Net. This cancer information website is produced by the American Society of Clinical Oncology known as ASCO, the world's leading professional organization for doctors that care for people with cancer.
In today's podcast, we'll discuss some of the research on head and neck cancers presented at ASCO's 2015 Annual Meeting. This podcast will be led by Dr. Ezra Cohen who is a Professor of Medicine and the Associate Director for Translational Science at the Moores Cancer Center at University of California, San Diego. Dr. Cohen is also an Associate Editor for Cancer.Net.
The ASCO Annual Meeting is the premier educational and scientific event where physicians, researchers and other healthcare professionals gather to discuss the latest in cancer care and treatment. This Cancer.Net podcast helps put new research findings into context and explains what they mean for patients. ASCO would like to thank Dr. Cohen for summarizing this research.
Dr. Cohen: Hi. My name is Doctor Ezra Cohen from the UC San Diego Moores Cancer Center. I'm a Professor of Medicine and an Associate Director for Translational Science. I'm going to talk to you about research in head and neck cancer today that was presented at the 2015 ASCO Annual Meeting. There were several highlighted research topics in head and neck cancer that I think are worth emphasizing and worth restating that although they may not influence immediate care for patients, they certainly are going to have an impact in the near future for how we treat this disease and how we manage patients with head and neck cancer.
The Annual Meeting consisted of several posters and abstracts that were presented by researchers along with several educational topics that were of interest to physicians treating this disease on a regular basis. What I'd like to do is really highlight 4 areas that I feel are relevant to not only today's practice, but the practice of treating these patients in the very near future. Those topics are going to include immunotherapy, de-intensified therapy, especially for HPV-positive disease, the use of PET scans in local events head and neck cancer, and the use of neck dissection or nodal dissection in patients with early stage disease.
Let me start by talking about a topic that's really been quite exciting in the recent past for not only head and neck cancer, but for almost every malignancy that we treat, and that is immunotherapy. We've known for a long time that immunotherapy may influence the behavior of cancer and in fact for diseases like melanoma, immunotherapies had been used for decades. The barrier has been primarily in other solid tumors and hematologic malignancies and that immunotherapies have been minimally effective and have usually carried quite a bit of toxicity. That all began to change in the last few years when newer classes of drugs were introduced into clinical trials and it began to appear that patients with all kinds of tumors were responding and that those responses were quite durable. That is, they lasted a long time.
Well, the same statements can be made for head and neck cancer and we saw data at this year's ASCO that at least for one class of drugs colloquially known as check point inhibitors, that efficacy or the ability of these drugs to shrink tumors produce responses can be quite profound and can last for a long time. Check points are naturally occurring breaks on the immune system that we all have and in fact are a necessary part of the immune system because as you can imagine, the immune system was designed to be turned on and to be activated when it sensed a foreign body or a virus, a bacteria, et cetera, a foreign organism, but then when that organism was destroyed to be quickly turned off so that the immune system doesn't damage the host and doesn't cause immune related diseases.
In some patients or for some diseases, we do see that—lupus, rheumatoid arthritis, and other auto-immune diseases—so we see the manifestations of when the immune system goes too far in a sense and begins to attack normal cells. One can imagine that there are natural breaks in place in the immune system to prevent that from happening. Well, cancer uses those natural breaks. In fact, can tell the immune system to not attack tumor cells and that's what some cancers do on a regular basis. Those signals that cancer uses, in some instances are called check points. Few years ago, we began to look at the use of check point inhibitors and these are usually antibodies that interfere with that signal for their ability to shrink cancers and to activate the immune system.
This year's ASCO, we saw a couple of abstracts, one of them presented on a large study using a drug called pembrolizumab, but did exactly that. It applied this drug called pembrolizumab in patients who had recurrent or metastatic disease, who were refractory to standard therapy. Usually, standard chemotherapy and exposed them to this single agent to see if there was any signs of activity. What we saw was that about a quarter of patients had responses and responses means significant shrinkage of the cancer. But more profoundly and perhaps more importantly, patients who had these responses appeared to respond for a very long time. In fact, the median duration of response or the average length of that response has not even been realized. We need the data to mature further in order to answer that question, how long do these responses last?
Well, we can say right now is that they seem to last for at least several months and potentially much more than that. The same is true of a similar drug called M-E-D-I or MEDI4736 that works on the exact same mechanism and we can say essentially the same things. The drug works by itself and when it does work, it appears to work for a very long time. As you can imagine, there's a lot of excitement around immunotherapy in head and neck cancer and currently, there are efforts underway to look at these drugs in larger studies against a controlled chemotherapy, in an effort to get eventually approval for these drugs in squamous cell carcinoma of the head and neck. Moreover, there are also efforts looking at combinations of these drugs with standard therapies such as radiation and chemotherapy or with other immunotherapies that may be able to further enhance the response and hopefully we'll be able to see those data at next year's ASCO Annual Meeting.
Moving on from immunotherapy, some interesting data were also presented about strategies to de-intensify curative therapy for patients with locally advanced squamous cell carcinoma of the head and neck. What we mean by de-intensification is the reduction in the aggressiveness of the therapy usually by reducing the dose or the volume or radiation therapy, but preserving cure rates. We've known for a long time that patients with HPV-positive head and neck cancer have substantially higher cure rates than their HPV-negative counterparts.
HPV, human papillomavirus is a causative agent for certain types of head and neck cancers—especially in the tonsils or the back of the tongue—and those cancers are treated routinely with chemotherapy and radiation, but the management of these patients is no different than with patients with tobacco-associated or HPV-negative disease. To that end, people began thinking that if we're able to cure HPV-positive patients at such high rates—rates approaching 90%—that perhaps we can begin to back off on the intensity of therapy to allow for fewer toxicities and especially better long-term functional outcomes, better long-term swallowing, speaking, et cetera, but of course maintain the cure rates. That's exactly what clinical trials did and we saw a couple of those efforts presented again at this year's ASCO.
One such study involved the reduction of the dose of radiation substantially and it turns out that for many patients with HPV-positive disease, this strategy appears to work, the strategy of using chemotherapy up front and in patients who have a very good response in the tumor using a much lower dose of radiation along with chemotherapy. This year's ASCO, we saw some of the functional outcomes of that approach in terms of quality of life and ability to swallow. It appears that in fact, it is possible to reduce the radiation dose in some of these patients and improve their quality of life in the long term. Another effort focused on reducing the volume of radiation in patients who had a good response to chemotherapy. Let me explain for just a moment what I mean by volume of radiation.
When we treat a patient with locally advanced head and neck cancer, the radiation oncologist will essentially draw 2 areas around the tumor. The first is called the planned treatment volume 1 and that basically encompasses all the cancer that we can see on scans. The second is planned treatment volume 2 and that encompasses areas that we see or at high risk of having cancer that is microscopic cancer, but of course we cannot see it on the scans. That would be the routine planning volume for a patient with head and neck cancer. What investigators at the University of Chicago did was, in patients who had a good response to initial chemotherapy called induction chemotherapy, those patients were only treated with that first volume—that is PTV1—and that second volume was completely eliminated.
In an effort to see, could we in fact reduce long-term side effects in these patients, but again preserve the high cure rates. In fact, in their poster presentation, they were able to demonstrate exactly that, that the cure rates appeared to be quite high in those patients that had a good response, but their functional outcomes was much better than the patients who had the complete radiation volumes. Functional outcomes, especially related to the ability to swallow and the ability to eat without a feeding tube. Both of these studies are certainly encouraging and now it's time to do larger, randomized trials of these types of approaches versus standard therapy and that's exactly the types of studies that are being planned, in a hope that we can one day treat patients with much less intensity, but of course preserving those very good cure rates.
A third trial or topic that was certainly interesting to discuss at ASCO was about the use of PET scanning in patients with locally advanced disease. In the United Kingdom, they enrolled a large study that asked the question of whether one can use a PET scan to essentially eliminate the need to do part of the surgery in patients with locally advanced disease. Again, let me explain a little bit more what I'm talking about. What we often do in patients who have a lymph node involvement of their cancer when they initially present is perform what's called a neck dissection, to try and remove all the lymph nodes that are affected. That can also be true in patients with large tumors, these are patients who would undergo an elective lymph node dissection to remove lymph nodes, again, in an effort to try and remove all the tumor.
Well, investigators in the United Kingdom asked the question, "Could we use PET scan after chemotherapy radiation to try and decide whether patients needed and neck dissection or not?" In fact, that's exactly what they did, they randomized patients to either receive the PET scan or to undergo neck dissection. What the investigators found was that using PET scan had very good accuracy in showing which patients needed a neck dissection, avoiding the need for a neck dissection in the great majority of patients without influencing survival. In other words, the use of PET scan was able to avoid surgery and provide the same cure rates, the same level of efficacy as not using a PET scan.
In a follow-up abstract that was presented right after the primary abstract, they also looked at cost effectiveness of this approach. It turns out that this was not only a surgical spearing approach by using PET scan, but it actually ended up costing less to the health system in the United Kingdom suggesting that it's a cost-effective approach as well. Many of us already use PET scans in this manner in patients with locally advanced disease, but it was certainly encouraging to see prospective data reassuring us that in fact, this does appear to be a valid strategy of using the PET scan to determine whether any further surgery needs to be done.
Then lastly, an interesting trial was presented at the plenary session of the ASCO meeting, looking at early stage oral cancer and the need for neck dissection. This was a study performed exclusively in India where oral cavity cancers are a very large problem and in fact, head and neck cancer makes up one of the most common cancers and the most common cancer seen in men in India. In India, this is a tremendous public health issue. What the investigators studied was the elective need for neck dissection versus a therapeutic neck dissection.
What's meant by that is when patients present with oral cavity cancers, we're faced with a question of whether to take out the lymph nodes or not. We can clearly see that there's a cancer in the oral cavity or let's say the tongue and what we cannot see—especially with small tumors or early stage tumors - is whether there's microscopic cancer in any of the lymph nodes. As you can imagine, microscopic cancer in lymph nodes is associated with a higher rate of recurrence and we would like to try and remove those if indeed they had cancer in them.
What the investigators in India did was they took patients with early stage oral cavity cancers and randomized them to either receive a neck dissection up front—that is that group underwent removal of the lymph nodes that were potentially involved with cancer—versus simply observation and removal of the lymph nodes only if they had evidence of cancer at any point. What the investigators found was that in fact, the therapeutic neck dissection—that is removing the lymph nodes up front—was associated with a lower recurrence rate and more effective cancer treatment. Suggesting that actually the current approach that's used in many centers—including many centers in the United States—appears to be the valid one. In patients with relatively early stage oral cavity cancers, a therapeutic neck dissection—that is taking out the lymph nodes up front—seems to be the more effective approach for treating these cancers. Again, a practice that's commonly done, but certainly heartening to see prospective data supporting our current practices.
There were of course a lot more data presented at ASCO that for the sake of time we couldn't cover today. It was a wonderful meeting with excellent discourse on many aspects of head and neck cancer. What I tried to highlight for you is four areas that either are going to, I think, dramatically impact the way we treat these patients in the very near future or the studies that have really reinforced what the standard therapy should be or the standard management should be for patients with locally advanced squamous cell carcinoma of the head and neck. Thank you for tuning in and listening to this podcast.
ASCO: Thank you Dr. Cohen. To find all of the science presented at ASCO's 2015 Annual Meeting, visit www.cancer.net. If you have questions about whether new research may affect your care, be sure to talk with your doctor.
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