Advances in Head and Neck Cancer with Dr. Paolo Bossi | OncoInfluencers

In this episode of OncoDaily, Dr. Paolo Bossi, Associate Professor of Oncology at Humanitas University, Milan, Italy, joins host Dr. Ravi Karra for an insightful discussion on head and neck cancers. Dr. Bossi delves into the latest advances in immunotherapy, supportive care, and personalized treatments in oncology. He highlights the importance of persistence in research, understanding treatment failures, and exploring new strategies for tackling challenging tumors like immune-cold cancers. Dr. Bossi also shares his journey, motivations, and the profound impact of mentorship in shaping his career in oncology.

Paolo Bossi is Head of the Head and Neck Medical Oncology Unit and Associate Professor of Medical Oncology at Humanitas University and Cancer Center. Previously, he served as an Associate Professor of Medical Oncology at the University of Brescia. His research focuses on head and neck cancers, especially rare types like paranasal sinus, nasopharyngeal, and salivary gland cancers. He has expertise in treating non-melanoma skin cancers and in leading trials on targeted and immunotherapy.

00:00 Recap
00:35 Introduction
02:20 From Nature to Medicine
03:50 From Loss to Oncology
06:30 Head & Neck Cancer
09:40 Immunotherapy Challenges
13:45 Immunotherapy Advances
17:45 De-escalating HPV Treatment
23:28 Cachexia Management Strategies
26:15 Multidisciplinary Approach Future
27:50 Conclusion

Ravi Karra: Welcome to today’s edition of OncoInfluencers. We are excited to have Dr Paolo Bossi with us today. Dr Bossi is an Associate Professor of Medical Oncology at the renowned Humanitas University and International Medical School based in Milan, Italy, built alongside the well-known Humanitas Research and Teaching Hospital.

Dr Bossi obtained his medical degree on oncology specialization from the University of Milan. He is well-recognized key opinion leader in head and neck cancers and non-melanoma skin cancers, as well as quality of life assessments and value-based medicines. He is particularly interested in rare cancers, including the paralyzing sinus cancer, nasopharyngeal cancer, and the cerebral gland cancer.

He is very committed to supportive care and is active in multiple organizations. He is currently the Chair of the Mucositis Study Group of the Multinational Association of Supportive Care and Cancer and also the President of NICSO, the Italian Supportive Care Group. He serves on the head and neck workstream of ESMO and is also the Chair of the Geriatric Subcommittee of the URTC Head and Neck Cancer Group.

He is an investigator in multiple clinical trials, both international and regional, and has contributed immensely to the understanding of cancer biology through his translational research activities. Dr Bossi, we are very glad to have you today.

Paolo Bossi: It’s a pleasure also for me. Thanks for this invitation.

Ravi Karra: Let’s start off by asking you a personal question. Please tell us more about yourself. Where are you from?
Where did you grow up?

Paolo Bossi: So, I come from a small city close to Milan, in a very green area. So, I grew up in the middle of the park, some very, very green area. So, it was very good for me, for my childhood, to spend time and to be close to the nature.

So, I like to put this walking, running, and going to the mountains. So, it’s a very, very nice area where I grew up. And so, that’s a good environment.

My family was not linked to medicine, so that’s a good thing for me. So, I started studying in the college and then I chose to become a doctor. It was almost a casual decision because I did not really choose medicine as my first option.
I would prefer to be a journalist, but at that time, there was no good school for journalists. So, at the end of the day, I chose to study medicine and I became very passionate about medicine. And then, so I became an oncologist after that.
So, telling a long history in one minute.

Ravi Karra: Excellent. And that already answers partly my second question, which is why did you choose medicine and especially oncology to specialize? And maybe you can tell us a bit more on how you started to focus on head and neck cancers, especially.

Paolo Bossi: Yeah, I believe that some of my colleagues have the same experience of myself. When my father died because of cancer, I was in the fifth year in medicine and I would like to study infectious disease because I was very passionate on this. But after this event, I asked myself how I can do something about this.

My father was very, very young, was 60 years old when he passed away. So, I tried to find something to, I don’t know, when you are young, you dream to change the world. I would like to change this bad part of my life, trying to do something against this.
And so, this was the real reason why I chose oncology as a main specialty for my specialization. Then after that, I studied oncology and I had the real luck to become a student in oncology under the supervision and the mentorship of Lisa Licitra, who was my mentor. And she’s a strong person.

She has a strong personality, but she’s very passionate for medicine. And so, she is an expert of head and neck cancer. So, that’s the reason why I also chose head and neck.
I specialized in oncology with the thesis of nasopharyngeal cancer under the mentorship of Lisa. And then after that, I was in the National Cancer Institute in Milan for more than 20 years. And then one day, Lisa told me, it’s time that you grow in another place.
So, she has a wonderful mentorship also for this, because she is able to encourage people to make choices. So, that’s really a great lesson for my life.

Ravi Karra: Oh, excellent. I think, well, I completely agree to that. And Lisa is a fantastic physician.
I cannot share fully in detail how much I learned from her. And of course, across the globe, you cannot have worked in head and neck cancer without knowing Lisa. So, hats off to Lisa there.
Great. The other question is, can you tell us a bit more about your current role and the specific tumor type you treat apart from head and neck cancer?

Paolo Bossi: Yeah. At the moment, I’m the chief of the head and neck medical oncology here in Humanitas University and in the Humanitas Hospital, which is linked to the university. And I’m guiding a group of four physicians and some translational researchers.

So, this is a mixed group where we try to perform the bench-to-bedside and bedside-to-bench research, trying to understand better the mechanisms, the molecular mechanisms of head and neck cancer, and trying to put in act some studies to counteract these mechanisms in all the settings of head and neck cancer. So, starting from the pre-malignant lesions, going to recurrent metastatic diseases. And apart from head and neck cancer, I treat also known melanoma skin cancer, so basically cutaneous squamous cell carcinoma, basal cell carcinoma, and a rarer form of cutaneous cancer like Merkel cancer or the neck cell cancer.

So, they’re very, very rare cancer in the skin, no, that are differently treated from melanoma cancer. So, the idea of this group is really to focus on these two types of diseases and try to increase the knowledge to educate people.

We are a centre where there are several meetings, educational meetings, congresses are organised by ourselves because we would like really to increase the resource and to focus on this specific cancer, because we know that this is a cancer that is usually, I’m speaking about head and neck cancer, usually it is not so well considered by the society, by the other physicians sometimes it is a really neglected cancer. So, we would like to offer, to increase the knowledge about this cancer and in the same time to try to discover new treatment modalities and to change possible the practice to increase survival in this type of cancer.

It’s really a challenge, sometimes I have to say that we lose many battles also in this disease and in the type of trials we are designing, we have lost many opportunities but we have also lost by fighting, so that’s something that reassures ourselves. So, we are trying to fight but only a few times you can succeed in this type of cancer. However, the real lesson is never give up studying and trying to learn from your failure, trying to increase the knowledge, trying to find out something more, to discover mechanisms, pathways and to discover how to better treat this type of cancers.

Ravi Karra: Okay, what are the latest treatment innovations in head and neck cancer, especially in the recurrent metastatic setting which I have seen over the decades has really been an area with a huge unmet need?

Paolo Bossi: Yeah, that’s really an unmet need because patients are suffering from this disease, are suffering from the burden of symptoms linked to this disease and the overall survival has been stuck on for many years, on less than one year. So, when you have a recurrent metastatic at the next common site carcinoma, you knew that at the median OS it was at one year and less. Now, with the new improvement in the immunotherapy, the combination of immunotherapy and the treatment sequencing, we are able to raise this bar and we have achieved 14-15 months of a median overall survival with the last trials that have been published.

So, I believe that this is the main challenge, this main novelty in the treatment of recurrent metastatic head and neck cancer. Try to integrate immunotherapy into the treatment journey. Then there is another important factor that we have not succeeded yet to discover and it is to identify biomarkers to understand who is the patient who should receive immunotherapy alone, who is the patient who should receive chemotherapy plus immunotherapy, who is the patient who will not gain any benefit from immunotherapy.

And linked to this discussion, there is the topic of how to increase the response to immunotherapy, how to make some immune-excluded tumours as immune-inflammed ones. Because we know that in these three categories, so the immune-inflammed, immune-excluded and immune-cold environment, what we could really tackle is the immune-excluded and immune-inflammed.

We have less weapons at the moment to act against the immune-cold tumours.
So, we have to concentrate on these two subtypes of tumours and try to understand how to ameliorate the treatment in this type of cancer. What we can do is try to implement with new strategies. We have immunotherapy, but lastly, we have new type of treatments by specific antibodies, combination of immunotherapy plus targeted agents, combination of immunotherapy plus therapeutic vaccines in HPV-positive recurrent metastatic patients.

So, these improvements represent the future for this group of patients. We have to invest our energy a little bit more. And what I strongly believe is that the research that came from the industry is very important.
We cannot do anything without the industry. We have to support the industry for this type of research, and that’s very good. But in parallel, we have to invest time, money, and research into the academic part of the research.

So, trying to identify biomarkers, trying to identify better sequencing, new combination, and new personalised treatment is typically part of the academic research. And we need more academic research in the head and neck field, in the head and neck cancer field. So, that’s something that I have learned during these years since I started my commitment with head and neck cancer, but these two types of research should go in parallel.
Sometimes they can meet together, but we have to put the same energy in two big fields of action.

Ravi Karra: Great. With respect to these immunotherapies, you also mentioned the bispecific T-cell receptor agents and so on. With all of these innovations taking place, what is the role of chemotherapy, radiotherapy, and chemoradiotherapy in head and neck cancer as of today?

Paolo Bossi: Yeah. Basically, what we know is that, at the moment, at least for locally-advanced cancer treated with a curative intent, what we know for the moment is that surgery plus chemoradiation or chemoradiation alone for locally-advanced disease maintains their role and they are still the benchmark for our intervention. So, the prognosis of our patient depends on these three main treatments, surgery, radiation, and chemotherapy.

So, that’s the treatment package that can give our patient best survival. However, the integration of immunotherapy, even in the locally-advanced setting, is something that could raise the bar of survival, could raise the bar of organ preservation and improvement in quality of life. Last week, we had the press release that has been released thanks to the results of the Keynote 689 trial that showed, at least according to these few sentences of the press release, that showed an event-free survival benefit for the group of patients randomized to receive immunotherapy before and after surgery.

So, that’s a completely new field. For the first time, we have a randomized trial in the locally-advanced setting showing a benefit for immunotherapy. In the past, we had a few trials, randomized trials, that failed to show an improvement of adding immunotherapy to radiation therapy and to radiation and chemoradiation.

So, the add-on immunotherapy to this benchmark, to this concurrent chemo rate, at the same time, is not useful, at least for the general population of head and neck cancer. But according to this last data, maybe putting immunotherapy before surgery and after surgery plus chemoradiation could be and should be a new treatment, a new choice that will increase event-free survival and, at the end of the day, overall survival. So, that’s a real challenge for us.

It’s important, a novelty for the field. It’s about 15 to 20 years that no new drug has appeared in the locally-advanced setting. I’m not speaking about metastatic, but in the locally-advanced setting, there was no news for this type of cancer and now we could really integrate something more.

This is just the beginning, maybe, of a new treatment approach that needs more and more research and needs more and more ideas for a better integration, but we know that we are quite reassured by the fact that this has helped some patients in that trial, so maybe it could help many, many other patients. So, we’ll see this data maybe in Congress next year and we’ll be able to elaborate a little bit more on how this particular field of research should go ahead.

Ravi Karra: We have seen in the past decades that the demography of the head and neck cancer patients in the Western world has slowly started to shift to more of a HPV-positive oropharyngeal cancer. So, this patient population has been increasing and we also know that this patient’s overall profile is a bit different to what used to be the historical head and neck cancer patients. Now, the question is, based on the current different kinds of immunotherapies and other treatment options available, are HPV-positive oropharyngeal cancer patients treated differently?

Paolo Bossi: Yeah, that’s the real question, the hot question for head and neck cancer specialists, how to deal with HPV-positive cancers. First, just to tell you that no randomized trial at this time exists showing that we can really safely de-escalate the treatment in HPV-positive cancer patients. Because this is the question, how, if you can gain real good survival in HPV-positive cancer but at the price of high toxicity, may we maintain, may we keep this good survival but reducing the amount of toxicity of the treatment?
This is the real challenge.

Now, we have different treatment approaches that have been studied and are in clinical trials at the moment. I would like just to cite some of them just to let you know how different is the scenario and the treatment paradigm where HPV-positive cancer can go.

So, let’s start from surgery. There are a few trials, one of the most important is the PATOS trial that is trying to put surgery since the beginning for HPV-positive cancer and try, thanks to surgery, to de-escalate the dose of radiation or try to avoid chemotherapy in the post-operative setting. This is a randomized clinical trial after surgery, all the patients receive surgery and then they have different type of randomization to answer this question.

So, this is the first trial. Another trial that has been recently presented at ASCO compared intensity-modulating radiation therapy with intensity-modulating protein therapy for this type of cancer and the other showed the same survival but less toxicity in particular for the swallowing and the nutrition. So, that’s just a few data but we can, that should be reinforced by other data to accept the fact that the protein therapy can help HPV-positive cancer patients.

Then we can move to the idea of identifying who are the patients who would receive less radiation and one of these methods would be identifying a biomarker and one of the possible biomarkers that has been recently presented is the hypoxia biomarker through F-mesopat.

This is a trial that has been presented recently at ASCO and a trial that is ongoing, a randomized trial is ongoing by evaluating after 30 grades of radiation who are the patients who maintain some hypoxic area who should receive high-dose radiation plus cisplatin and who are the patients that after 30 grades of radiation are completely negative for the hypoxic microenvironment. So, this patient may safely receive only 30 grades of radiation and two doses of cisplatin.

So, this patient really de-escalated. So, let’s think 30 grades against 70 grades and the recent data presented by Nancy Lee at ASCO showed that this is a very, very interesting way to proceed for a randomized clinical trial. So, the trial has just started and in a few years I believe that the enthusiasm towards this biomarker will increase.

So, that would be the first way to tailor the treatment according to this biomarker. Another biomarker that is really very, very interesting is the CTDNA, HPV CTDNA, cell-free DNA that could identify the patient that at a certain part of the treatment are negative for the circulating DNA. So, it means that this patient maybe can be safely de-escalated or the patient who need to stay on the highest dose of the treatment because they maintain a liquid biopsy positive.

And so, we should aim at increasing the dose of and maintaining the high dose of radiation there. So, these in a nutshell are the type of treatments that I would identify as being promising for the future for HPV. Just one minute to tell you that not all the HPV positive are created equal because we have some T4 and N3 disease where something more would be done.

These are the patients that should not be de-escalated but maybe should be escalated. And for this patient, receiving immunotherapy sometimes, maybe before or before and after, could be a reasonable choice for the future. So, you can see how multi-faceted is the treatment approach to HPV positive cancer for the future.
And it’s a really challenging and exciting part of the question, I would say.

Ravi Karra: Thank you. Now, shifting gears a bit, you play a very important role in the Multinational Association for Supportive Care of Cancer. You’re also the president of the supportive care network in Italy.
We know that one of the patient groups that has been, let’s say, neglected to a certain extent is patients suffering from cachexia. What is new for these patients? Is there some hope for cachexia patients?

Paolo Bossi:  Yeah. Cachexia in head and neck cancer has two basic causes. The first one is the disease, as you know, that prevent people from eating and swallowing.
So, that’s the causes of anorexia and the weight loss sarcopenia. And the other cause is the treatment. Chemoradiation is one of the treatment that causes the highest weight loss and also the muscle loss.

So, it’s very aggressive treatment, I would say. So, we encourage our colleagues to put in any of the strongest supportive care since the beginning. So, the nutritional evaluation, the nutritional support, starting from the rehabilitation of this patient.
So, before starting radiation or before surgery, that’s really a crucial point for ourselves, for our patient, because it’s important to support this patient. This, I believe, is the most important and key factor we try to support since the beginning. Then, for the future, there is a possible compound that’s really promising for me.

It’s the history of ponsegromab. It’s a drug that acts against the GDF-15 that has been shown as a biomarker, as an actor of causing cachexia and causing stress to the body, acting during the processes that cause stress to the body and causing, at the end of the day, cachexia. So, this drug acts against GDF-15 that is elevated in head and neck cancer, very high in head and neck cancer, before and during the treatment.

So, this is a possible drug that could support this type of patient. There are randomized clinical trials ongoing in other diseases, pancreatic lung cancer and colon cancer, but I believe that head and neck cancer is one of the fields where this drug could also help a lot of our patients. The story has to be written.

I believe that we will write a strong part of this history as a head and neck cancer specialist, and I believe that this is another brick to be added to increase the support of care to our patients, and at the end of the day, to ameliorate quality of life and improve overall survival in this group of patients.

Ravi Karra: It’s very good to hear that. And one final question is, what is your message to the head and neck cancer patients out there? What can they look forward as treatment options in the next decade?

Speaker 1
So, my main message is that head and neck cancer should be dealt, should be discussed in a multidisciplinary way in centers with expertise and numbers for treating this type of cancer. We have data clearly saying that the importance of the expertise of the group that is treating head and neck cancer patients. This is my main message that’s very important.

What I look for the future is having more compounds, more drugs, and being able to integrate in a multidisciplinary way these compounds by a good treatment sequencing in every setting of disease. So, just my last message, I believe that the history of head and neck cancer starts from the oral potentially malignant diseases. So, since the beginning, if you are able to intercept this type of disease and to prevent the malignant transformation, and there are many studies and trials ongoing, we are really fighting in this field that I believe is one of the major parts for having less patients with head and neck cancer and to be able to intercept the cancer transformation.

So, these are the fields of action for the future where we may be able to reduce the burden of disease at the end of the day, improve the prognosis of this type of patients.

Paolo Bossi:  With that, thanks a lot for the message. I sincerely hope that this is what we work towards in the future. I would like to thank you very much for your time and for all the insights you gave us.
Thanks a lot and have a nice rest of the day.