Evolve Advanced Non-Melanoma Skin Cancer Resource Guide

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Questions to Ask About Your Advanced Non-Melanoma Skin Cancer Treatment Plan

Questions to Ask About Your Advanced Non-Melanoma Skin Cancer Treatment Plan from Patient Empowerment Network on Vimeo.

Are there key questions that advanced non-melanoma skin cancer patients should ask about their treatment plan? Dr. Anna Pavlick provides expert advice, emphasizing the importance of discussing treatment milestones and exploring alternative options if needed.

Dr. Anna Pavlick is a medical oncologist and the founding Director of the Cutaneous Oncology Program at Weill Cornell Medicine and NewYork-Presbyterian. Learn more about Dr. Pavlick.

See More from Evolve Non-Melanoma Skin Cancer

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Treating Non-Melanoma Skin Cancer With Targeted Therapies


Transcript:

Katherine:

What questions should patients be asking about their proposed treatment plan? 

Dr. Pavlick:

I think it’s important to obviously know everything that you can about the medicine that you’re going to be given. What are the side effects? How does it work? Is it pills? Is it IV? Are you injecting something into me? In addition to that, I think patients also need to ask, “Well, how are you going to know that it’s working? When do we do scans? When do I get reevaluated?” Because again, not everybody is going to respond to every therapy. If we did, listen, I would retire and open up a dog reserve. But what is the milestone? 

How many cycles or how long before we determine this is working or this isn’t working? And many times, because patients have visible lesions on their skin, it’s not really hard to know whether something is working or not because you’re going to watch it get better or you’re going to see it get worse.

And many times, when patients ask me that, my answer is we have to see as we go along. But if we see it getting better, we keep going until it’s gone or it just stops shrinking. And then we talk about maybe removing it. On the contrary, if we give patients medicine and after let’s say two treatments, this spot on their skin has increased in size and looks like it’s growing, well, maybe we want to stop and reconsider what we’re doing and change to something different.  

What Are the Advantages of Seeing a Specialist for Skin Cancer?

What Are the Advantages of Seeing a Specialist for Skin Cancer? from Patient Empowerment Network on Vimeo.

What are the advantages of seeing a skin cancer specialist? Dr. Anna Pavlick highlights how specialists offer expertise in managing complex cases, like large lesions or tumors with associated lymph nodes, ensuring up-to-date treatment and collaborative care with local physicians.

Dr. Anna Pavlick is a medical oncologist and the founding Director of the Cutaneous Oncology Program at Weill Cornell Medicine and NewYork-Presbyterian. Learn more about Dr. Pavlick.

See More from Evolve Non-Melanoma Skin Cancer

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When Should Clinical Trials Be Considered for Advanced Non-Melanoma Skin Cancer Treatment?

When Should Clinical Trials Be Considered for Advanced Non-Melanoma Skin Cancer Treatment?

Questions to Ask About Your Advanced Non-Melanoma Skin Cancer Treatment Plan

Treating Non-Melanoma Skin Cancer With Targeted Therapies

Treating Non-Melanoma Skin Cancer With Targeted Therapies


Transcript:

Katherine:

What is the advantage of someone seeking care or to have an appointment with the skin cancer specialist?  

Dr. Pavlick:

Although for me, skin cancer is my life, skin cancers to the point where they require a medical oncologist are not all that common. Basal cell cancer and squamous cell cancer are very, very common in our population, but many times, they are managed by the dermatologist where you have an excision or you have a Mohs procedure. You don’t ever need to see an oncologist. However, if you have a very large lesion or you’ve got a lesion and you’ve got an associated lymph node or you’ve got a lesion that has what we call satellites or little tiny, I call them cousin tumors surrounding the primary lesion, you’re going to get referred to a medical oncologist.  

And many oncologists in the general community may or may not be very familiar with the up-to-date management because it’s not very common. The common cancers out there are breast cancer, lung cancer, colon cancer, prostate cancer. And general oncologists are very well-versed in how to manage those. I tell most patients you may not need to come to a big skin cancer referral center, but it may benefit you to come for an opinion and have a skin cancer oncologist work with your local doctor.  

And I do this all the time. Folks will come in and say, “You’re in New York City, but I live out in New Jersey. And coming into the city is just such a hardship. Is there any way I can do this outside?” And many times, my answer is if you’re not going to be participating in a clinical trial which is being run at my institution, I am more than happy to talk to your oncologist and work with them.

And it’s a collaboration. Many of us in academia are not looking to steal patients. We’re just looking to provide patients with the highest quality standard of care and are very, very happy to work with anybody that will provide that care to the patient to make sure that the patient can also get that care in a non-stressful setting.  

When Should Clinical Trials Be Considered for Advanced Non-Melanoma Skin Cancer Treatment?

When Should Clinical Trials Be Considered for Advanced Non-Melanoma Skin Cancer Treatment? from Patient Empowerment Network on Vimeo.

When should clinical trials be considered for advanced non-melanoma skin cancer treatment? Dr. Anna Pavlick explores the role of clinical trials, common patient concerns about participating in trials, and the phases of clinical trials in cancer research.

Dr. Anna Pavlick is a medical oncologist and the founding Director of the Cutaneous Oncology Program at Weill Cornell Medicine and NewYork-Presbyterian. Learn more about Dr. Pavlick.

See More from Evolve Non-Melanoma Skin Cancer

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Advanced Non-Melanoma Skin Cancer Research Update

Advanced Non-Melanoma Skin Cancer Research Update

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How Does Immunotherapy Treat Advanced Non-Melanoma Skin Cancer?

Treating Non-Melanoma Skin Cancer With Targeted Therapies

Treating Non-Melanoma Skin Cancer With Targeted Therapies


Transcript:

Katherine:

Where do clinical trials fit into a treatment plan for advanced non-melanoma skin cancer? 

Dr. Pavlick:

Again, my feeling is that clinical trials are opportunities for patients to be able to not only get the standard of care because many of our clinical trials offer patients the standard of care which is immunotherapy. 

But then we look to add something. And by adding something, can we make the responses faster, better, more durable? And that’s why asking your oncologist or your dermatologist about is there a clinical trial that I may be eligible for may make a huge impact on what happens.

We talked about immunotherapy. We talked about the targeted therapy. There are clinical trials that are now looking at injecting tumors with viral vectors. So, by injecting, we’re using the herpes virus which is the cold virus and injecting that directly into the lesion. Can that generate a better immune response to make things shrink up faster and provide more durable responses? 

And so, those are very exciting things. Most of these non-melanoma skin cancers have not metastasized. And even if they have, we’ve seen that if you inject the lesion that’s cutaneous, even if you have something that’s deeper, by really stimulating an immune response, you can not only contain the lesion that you’re injecting, but you will get a reciprocal response in the other lesions as well. So, it’s really a neat concept that’s really coming to fruition. 

Katherine:

What would you say to a patient who is hesitant in participating in a trial? 

Dr. Pavlick:

What do you got to lose? Patients are always very concerned that when they participate in a trial that they will get a placebo.  

Katherine:

Yeah. 

Dr. Pavlick:

And I think that’s the biggest hesitation and the biggest concern for many patients.  

And that has to be spelled out in the trial. The trial is going to say this is a trial where half of the patients are going to get a placebo or half of the patients are going to get X medicine. It is exceedingly rare in a treatment trial that there will be a placebo arm. Many times, if you’re talking about prevention, those are the studies that will want a control arm to get a placebo because the standard of care is you take this out, you do nothing and you watch.

Well, if you’re looking to see if doing something versus nothing is better, then they’re going to tell you. The standard is care is that we do nothing. However, in this trial, half the patients are going to get watched and get the standard of care. 

The other half of the patients are going to get either drug X or drug Y. And then at the end of the study, we’re going to see if those medicines actually benefited or didn’t benefit those patients compared to the patients who were just watched. Most patients who have active disease, whether it be locally advanced or metastatic are going to be offered trials that are either what we call a Phase I, a Phase II or a Phase III study.

So, a Phase I study is where we’re taking a brand new medicine that’s coming from the lab that looks to be very exciting. And we’re looking for what the side effects are and what is the right dose. So, it’s a very early trial where we’re not even sure what the toxicity is or what’s the right dose.  

Once we complete Phase I studies, we then get the information. So, we know the right dose. We know the side effects. We move onto a Phase II study. So, a Phase II study is where we’re going to look at a particular type of cancer and say everybody gets this drug at this dose and we know what the side effects are. We are looking to see if it truly is efficacious because from our very early research in the Phase I studies, we saw a group of patients with this particular type of cancer have a really nice response. And so, we’re looking for the efficacy of a drug in a Phase  II study. So, everybody gets treated. If we find something in the Phase II study that is a slam-dunk oh, my goodness, this looks terrific, we then go on to a Phase III study.

And so, a Phase III study is a randomized trial meaning half of the patients get one treatment. Half of the patients get the other treatment. Many times, I don’t get to pick what the patient gets. The patient doesn’t get to get what the patient picks. It’s randomized, but everybody gets a treatment. And Phase III studies take this new drug that we saw and got very excited about in the Phase II study, and we’ll compare it to the gold standard or the current standard of care for that particular disease. And then we compare the standard to the new treatment and see who wins. And that’s how we advance our learning. We advance what we do for people with this disease because if the new treatment does better than what we’re doing for everybody else, well now everybody else is going to get the new treatment.  

Treating Non-Melanoma Skin Cancer With Targeted Therapies

Treating Non-Melanoma Skin Cancer With Targeted Therapies from Patient Empowerment Network on Vimeo.

Dr. Anna Pavlick discusses targeted therapy, specifically hedgehog inhibitors for basal cell cancers, explaining how these therapies block cancer growth pathways, their rapid effectiveness, and potential side effects.

Dr. Anna Pavlick is a medical oncologist and the founding Director of the Cutaneous Oncology Program at Weill Cornell Medicine and NewYork-Presbyterian. Learn more about Dr. Pavlick.

See More from Evolve Non-Melanoma Skin Cancer

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When Should Clinical Trials Be Considered for Advanced Non-Melanoma Skin Cancer Treatment?

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What Are the Advantages of Seeing a Specialist for Skin Cancer?


Transcript:

Katherine:

How do targeted treatments to treat non-melanoma skin cancer?  

Dr. Pavlick:

Targeted therapies are approved for basal cell cancers in particular. They are certainly not for squamous cell or Merkel cell, but basal cell because basal cell cancers use a pathway called the patched and the smoothened pathway to multiply and metastasize or spread to other parts or just continue to grow.

And hedgehog inhibitors will inhibit that or block that particular pathway. These pathways are so highly overexpressed in basal cell cancers that we don’t even need to check when we do a biopsy. We don’t routinely check and send the biopsy to see if these tumors have those pathway alterations because 99.9 percent of them do. 

And so, we can easily give this targeted therapy to a patient with basal cell cancer. The nice thing about giving a targeted therapy is like shutting off a light switch. If the light is on and the cancer is using this pathway, if you shut the switch or block that pathway, things get better very, very quickly. Part of the downside to some of these hedgehog inhibitors are some of the side effects. Because basal cell cancers occur in older populations, these are patients that may in fact be sicker or more frail. And two of the side effects that can occur from hedgehog inhibitors is alteration in taste and the feeling that you’re just not hungry. 

So, anorexia and if you’ve got a thin frail patient and now you give them something that’s going to deter them from eating even more, they may be problematic. And not everybody gets those, but those are the most concerning. Patients do have a chance of having hair thinning or hair loss with hedgehog inhibitors. Another reason why many people just will say to me, “I don’t want them even though it will respond faster. I’d rather be treated with immunotherapy because then I’m not going to lose my hair.” And for a lot of women no matter what your age is, hair is an important part of who you are.  

Katherine:

Yeah.  

Dr. Pavlick:

And the last other significant side effect of hedgehog inhibitors is muscle cramps. And many times, this will happen in the middle of the night. People get really bad charley horses. 

I have patients who say they get cramps in their fingers or cramps in their hands. It’s not as easy to manage. We do know that sometimes by giving patients a medicine called amlodipine which is commonly used for blood pressure, this may help resolve or reduce the number of cramps they get, but it doesn’t work for everybody.

And so, you kind of have to balance out how quickly do you need this cancer to go away or respond? Because if you do use a hedgehog inhibitor, you’re going to get a very rapid response. If you use immunotherapy, just think about it. You’ve got to wake up your body’s immune system. You’ve got to get those T cells to get moving. And so, responses are not going to be in a matter of days. It’s going to more in a matter of weeks. With the hedgehogs, your responses are seen in a matter of days. 

Katherine:

Wow. So, sometimes, it could be a difficult decision to make?  

Dr. Pavlick:

Yeah, you have to weigh out pros and cons. Sometimes, you have patients who can’t swallow pills. Well, if you can’t swallow a pill, then a hedgehog inhibitor is not on your list of things that you can take. And to the contrary, some people are just really averse to having to come in and get an infusion because they may have needle phobia or they just don’t want an IV infusion. And then a hedgehog inhibitor is your first line of therapy.  

How Does Immunotherapy Treat Advanced Non-Melanoma Skin Cancer?

How Does Immunotherapy Treat Advanced Non-Melanoma Skin Cancer? from Patient Empowerment Network on Vimeo.

How does immunotherapy treat advanced non-melanoma skin cancer? Dr. Anna Pavlick delves into the mechanisms of immunotherapy and common side effects.

Dr. Anna Pavlick is a medical oncologist and the founding Director of the Cutaneous Oncology Program at Weill Cornell Medicine and NewYork-Presbyterian. Learn more about Dr. Pavlick.

See More from Evolve Non-Melanoma Skin Cancer

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When Should Clinical Trials Be Considered for Advanced Non-Melanoma Skin Cancer Treatment?

When Should Clinical Trials Be Considered for Advanced Non-Melanoma Skin Cancer Treatment?

Advanced Non-Melanoma Skin Cancer Research Update

Advanced Non-Melanoma Skin Cancer Research Update

Treating Non-Melanoma Skin Cancer With Targeted Therapies

Treating Non-Melanoma Skin Cancer With Targeted Therapies


Transcript:

Katherine:

Dr. Pavlick, would you explain how immunotherapy uses a patient’s own immune system to treat cancer in the body? 

Dr. Pavlick:

Sure. Immunotherapy is very, very different than chemotherapy. As you know, with chemotherapy, chemotherapy is designed to attack rapidly dividing cells. And so, cells that are rapidly dividing are also some of your immune cells. 

And so, patients can get anemia. They can get problems where they’re at risk of infection because the bone marrow if moving very quickly. Immunotherapy on the other hand really doesn’t affect any cells that are rapidly dividing. I like to tell patients it wakes up their immune system. We all have what we call T cells that are living in our lymph nodes.

And immunotherapy really stimulates the body to produce more of those killer T cells and those memory cells and those cells that are out there to go and attack cancer and also creates memory. If, in fact, there is a cell that may be hiding or what we call dormant, if that cell were to decide it’s time to wake up and start growing, your immune system is going to remember the proteins that are on that particular cell and wake up your body’s immune system again to attack that cancer cell before it becomes a tumor. 

And so, that’s what we see with immunotherapy is when people have very dramatic responses and their immune system is able to eradicate their cancer, many times it’s a lifelong durable process. And so, because that immune system is constantly upregulated and on surveillance, we think that this translates into why people do so well for so long.  

Katherine:

So, which advanced non-melanoma patient type is immunotherapy right for? 

Dr. Pavlick:

Pretty much all of them.  

Anti-PD1 therapy, this is the most common type of immunotherapy that we use for non-melanoma skin cancers. And they’re approved for squamous cell cancer, basal cell cancer, Merkel cell, all very, very highly active and produce really impressively good results with long-term durable responses. So, sometimes when we talk about basal cell cancer, there are two types of therapies that we can talk about when it comes to basal cell.

We talk about immunotherapy, but we also talk about targeted therapies which are the hedgehog inhibitors. And there are pros and cons to both types of treatments, but when it comes to basal cell, we’ve got those two options. When it comes to Merkel cell and squamous cell, our first go-to option is really immunotherapy with anti-PD1 agent.  

Katherine:

But I wanted to know what the common side effects are for using immunotherapy to treat non-melanoma skin cancer. 

Dr. Pavlick:

Sure, when it comes to what we call adverse events or side effects from immunotherapy, when we give patients these single-agent anti-PD1 medicines, the chances of them having side effects are probably in about the 20 percent range. So, there’s a very large proportion of patients who are coming into the office getting these treatments and never have one side effect. But if you’re going to have any side effects, the most common side effects can be rash or itching.  

They don’t need to be together, so you can have a rash that doesn’t itch. You can itch and not have a rash. Those are really the skin toxicities. Sometimes with prolonged treatment, some patients may develop an underactive thyroid gland because the immune system will also attack some of the thyroid cells and slow down its function.

And so, those patients need to be given thyroid medicine. Fortunately or unfortunately, that’s one of the side effects that is a not-reversible side effect. And so, if we slow down your thyroid, you’re going to be committed to taking thyroid medicine for the rest of your life, which is essentially one tiny little pill every morning. But patients do need to know that. These drugs get metabolized by the liver and the kidneys. 

And so, before we give patients their infusion, we always check their liver and their kidneys to make sure that the immunotherapy hasn’t caused an inflammation of the liver or an inflammation of the kidneys making it not safe to give immunotherapy at that point in time. It doesn’t mean that we can’t go back and give it again. We just need to let those organs recover. Give them medicines to calm down the inflammation and then we can resume treatment.

Any time you give patients an immunotherapy, the side effects can be very vast because they cause inflammatory side effects. So, anything that you can put an -itis on the back of it, so dermatitis meaning inflammation of the skin, colitis meaning inflammation of the colon which can lead to diarrhea or bloating or a feeling of some baseline nausea if it affects the small bowel instead of the large bowel. 

Pneumonitis is an inflammation of the lungs. Any kind of -it is, one of the more rare things is what we call uveitis and it’s an inflammation of the back of the eye where it makes it difficult for patients to see, very easily diagnosed by an ophthalmologist and treated with either steroid eye drops or a short course of oral steroids that will get everything calmed down. And even if that happens, it doesn’t mean that you can’t go back and retreat those patients. So, any type of inflammatory symptom is a potential side effect.  

Advanced Non-Melanoma Skin Cancer Research Update

Advanced Non-Melanoma Skin Cancer Research Update from Patient Empowerment Network on Vimeo.

Dr. Anna Pavlick highlights ongoing research into preoperative immunotherapy in non-melanoma skin cancer. Dr. Pavlick emphasizes the importance of clinical trials and provides guidance on how to inquire about participating in these studies.

Dr. Anna Pavlick is a medical oncologist and the founding Director of the Cutaneous Oncology Program at Weill Cornell Medicine and NewYork-Presbyterian. Learn more about Dr. Pavlick.

See More from Evolve Non-Melanoma Skin Cancer

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When Should Clinical Trials Be Considered for Advanced Non-Melanoma Skin Cancer Treatment?

When Should Clinical Trials Be Considered for Advanced Non-Melanoma Skin Cancer Treatment?

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What Are the Advantages of Seeing a Specialist for Skin Cancer?

What Are the Advantages of Seeing a Specialist for Skin Cancer?


Transcript:

 Katherine:

What research is showing promise? What are you excited about? 

Dr. Pavlick:

Oh, my goodness. Skin cancer research is really skyrocketing. 

We have been able to use immunotherapy. Again, we developed this in metastatic melanoma but have really looked at the large-tumor mutational burden that squamous cell and basal cell cancers have as well as Merkel cell and have been able to take immunotherapy from one setting and apply it to the next setting.

And we’ve seen some really spectacular results. Many times, we were just using immunotherapy to treat these malignancies, but the thought process has been well, what happens if we move it sooner and we give it to patients before we take them to the operating room?  

So, I think the thing that’s really been exciting has been looking at giving immunotherapy prior to surgery rather than giving it as prevention after surgery. 

And the reason we found that very meaningful is that we did a clinical trial giving patients somewhere between two and four cycles of preoperative treatment. And then we took them to the operating room which gave us the opportunity to look at that tumor and see what the immunotherapy did to the cancer. And a very high percentage, more than 50 percent of those patients were found to have no cancer whatsoever left in the specimen that was removed from their body.

And so, now we’ve got studies going on saying since patients have the potential to do so well with immunotherapy before surgery, A, do we even need to do surgery? B, if we do take them to the operating room, do we need to give them more preventive immunotherapy or can we just say you had such a great response, you’re done with treatment? 

 

And so, there is lots of exciting things that we’ll be identifying within the next few years that really, I think, is going to make a huge impact on patient’s lives. If we find out that immunotherapy can eradicate cancers, we may prevent people from having to go to the OR for resection. So, stay tuned for that, very exciting.   

Katherine:

How can patients learn more about research? What sorts of questions should they be asking their healthcare team?  

Dr. Pavlick:

I think research to me is always an opportunity because this is how we move science forward. 

So, I think whenever a patient is given a diagnosis of a cancer, whether it be an early-stage cancer or a later stage cancer, I think their physicians are obligated to really talk to them about clinical trial options for them.  

And sometimes, in early-stage cancers, there aren’t any. But sometimes there are prevention studies that may be taking place that once they get the diagnosis, they get treated for their cancer. They may be eligible to participate in prevention studies. So, I think that should always be a question that patients ask is, “Okay, other than the standard of care, are there any research studies that I may want to consider or need to know about?”  

Advanced Non-Melanoma Skin Cancer: Tackling Obstacles to Care

Advanced Non-Melanoma Skin Cancer: Tackling Obstacles to Care from Patient Empowerment Network on Vimeo.

While advanced non-melanoma skin cancer treatments are available, some patients may still encounter difficulties accessing quality care. Dr. Diwakar Davar discusses common obstacles to care, social determinants of health, and the future of advanced non-melanoma skin cancer research. 

Dr. Diwakar Davar is the Clinical Director of the Melanoma and Skin Cancer Program at UPMC Hillman Cancer Center. Learn more about Dr. Davar.

Download Guide

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What Are the Potential Benefits of an Advanced Non-Melanoma Skin Cancer Clinical Trial

What Are the Potential Benefits of an Advanced Non-Melanoma Skin Cancer Clinical Trial? 


Transcript:

Katherine:

It’s not always easy to access the latest treatments or to find a specialist. I’m wondering what the common obstacles patients face in accessing the best care. 

Dr. Davar:

Some of the major issues are access to highly specialized treatment centers. Across the entire United States, there are clearly comprehensive cancer centers where the NCIS designated these places as being areas where patient care can deliver clinical trials available.  

Oftentimes, there is the breadth of research all the way from population research all the way to clinical trials. Not everybody has access to a comprehensive cancer center. Some patients may be living in a geographical location that is remote. Some patients could be living in a location that is not necessarily remote from a comprehensive cancer center, but may have social determinants of health that make it hard for them to access these comprehensive cancer centers. The only way around this is information.  

Patients need to be able to access information in a fashion that is both trusted, and up-to-date, and secure so that they are enabled and equipped with the right information for them to be able to have informed discussions about their care with their providers. 

Katherine:

This is all such great information, Dr. Davar. As we wrap up, I would like to get your thoughts.  

How do you feel about the future of advanced non-melanoma skin cancer research? 

Dr. Davar:

I am actually extraordinary optimistic about this landscape. When I started out as an oncologist, my big focus was in melanoma. I very quickly realized that most of the excitement was certainly, while in melanoma, was being generated, it was actually spilling over into non-melanoma skin cancer and the primary reason for that is the unique patient level challenges that make this disease a difficult disease to treat. The patient age, the comorbidities, the fact that a vast majority of our patients had gotten transplants, and that resulted in a relative contraindication of the administration of the effective agents that were developed that eradicated the majority of this disease.  

What oftentimes is a challenge, what is one man’s challenge is another man’s potential cure and it’s a potential benefit in an area in which it could be studied.  

What we realize about these challenges is they actually give us opportunities and avenues for research. As we think about non-melanoma skin cancer, we realize that this is an area in which there is tremendous potential where you can potentially give people immune therapy and improved outcomes, but not just improve patient outcomes in making people live longer, but also by reducing the burden of care by reducing the amount of surgery and radiation that people need that enables people to not just live longer, but live longer and maintain their quality of life as they age, and allows them to age with dignity. 

Advanced Non-Melanoma Skin Cancer Treatment: Understanding Personalized Medicine

Advanced Non-Melanoma Skin Cancer Treatment: Understanding Personalized Medicine from Patient Empowerment Network on Vimeo.

Treatment for advanced non-melanoma skin cancer is becoming more personalized, but what does that mean exactly? Dr. Diwakar Davar defines personalized medicine and reviews key factors involved in determining skin cancer treatment options.

Dr. Diwakar Davar is the Clinical Director of the Melanoma and Skin Cancer Program at UPMC Hillman Cancer Center. Learn more about Dr. Davar.

Download Guide

See More from Evolve Non-Melanoma Skin Cancer

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An Expert’s Perspective on Advanced Non-Melanoma Skin Cancer Research

An Expert’s Perspective on Advanced Non-Melanoma Skin Cancer Research

Emerging Treatments for Advanced Non-Melanoma Skin Cancer: What’s Showing Promise

Emerging Treatments for Advanced Non-Melanoma Skin Cancer: What’s Showing Promise?

Advanced Non-Melanoma Skin Cancer: Tackling Obstacles to Care

Advanced Non-Melanoma Skin Cancer: Tackling Obstacles to Care


Transcript:

Katherine:

You know, Dr. Davar, we often hear this term “personalized medicine.” What does it mean? 

Dr. Davar:

Personalized medicine really means individualizing the patient’s treatment for that particular patient’s tumor. No two tumors are the same. Every tumor is different just as every person is different. Therefore, identifying and crafting the optimal treatment plan really involves identifying the most available and up-to-date information about the person’s tumor and contextualizing the treatment options in that setting.  

For example, in the context of Merkel cell polyoma, the virus associated with Merkel cell carcinoma, the treatment options would certainly include checkpoint inhibitor therapy with the understanding that the Merkel cell polyomavirus status could change both the response to the treatment but also the monitoring of the treatment because there is and acid that uses antibody titers to track the disease.  

In the context of patients with advanced cutaneous squamous cell carcinoma, the presence or absence of intratumoral CD8 T cells very provocatively can affect the response of checkpoint inhibitor therapy. The key thing to understand about personalized medicine is the more information we have about your tumor, the more informed we are about not only your current treatment, but also what future treatments might be available to you if the current treatment stops working. 

Katherine:

Aside from testing, what other factors are involved when choosing therapy? 

Dr. Davar:

These factors include, particularly for non-melanoma skin cancers, the patient’s age and performance status. We do know that as patients get older, their comorbid piece changes. They have a higher risk of having concomitant second illness such as cardiac issues, diabetes, high blood pressure, cholesterol issues, strokes, and coronary artery disease.  

These diseases in and of themselves do not necessarily affect one treatment choice over another, but it may change how you treat the patient. For example, a 60-year-old patient with melanoma may be a great surgical candidate. A 60-year-old patient with squamous cell carcinoma maybe a great surgical candidate. However, an 85-year-old patient with cutaneous squamous cell carcinoma with a tumor near the eye may not necessarily be a great surgical candidate because even though the tumor could be removed, it would result in the removal of that person’s eye.  

If this person has already has got, for example, age-related issues with balance, age-related issues with difficulty and vision and depth perception, removing this person’s eye, which is a very morbid procedure, but can be done at relatively low surgical risk, could really affect this patient’s quality of life and may force you to rethink what you would do and may result in you offering this patient a different treatment modality such as upfront use of systemic therapy rather than a standard surgical approach.  

The idea is that the more information you have about the patient, the easier it is to contextualize the treatment for a particular patient and particularly in the context of non-melanoma skin cancer, which often time happens to patients who are, on average, one decade older than patients with melanoma. Taking their age and taking their comorbid conditions is very important in determining the treatment modality and also in making individualized patient recommendations. 

What Are the Potential Benefits of an Advanced Non-Melanoma Skin Cancer Clinical Trial?

What Are the Potential Benefits of an Advanced Non-Melanoma Skin Cancer Clinical Trial? from Patient Empowerment Network on Vimeo.

Clinical trials are an option for some advanced non-melanoma skin cancer patients, but what are the potential benefits? Dr. Diwakar Davar shares his perspective on why patients should consider trial participation.

Dr. Diwakar Davar is the Clinical Director of the Melanoma and Skin Cancer Program at UPMC Hillman Cancer Center. Learn more about Dr. Davar.

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What Is Advanced Non-Melanoma Skin Cancer and How Is It Staged?

Advanced Non-Melanoma Skin Cancer: Who Is on Your Healthcare Team?

Advanced Non-Melanoma Skin Cancer: Who Is on Your Healthcare Team?


Transcript:

Katherine:

Dr. Davar, thank you for that detailed information. It is really valuable. You mentioned, a few moments ago, clinical trials. What are the benefits of participating in a clinical trial? 

Dr. Davar:

Well, the first and the most important benefit of participating in a clinical trial is that oftentimes, your team is larger. Normally, a patient has a doctor. We have a PA and we have a nurse taking care of them. When you have a clinical trial, at that clinical trial, you have three, four, five times that number of people taking care of you. There are research nurses, research coordinators, nurse navigators, and all of these people are looking over your chart helping the doctor cross-check and check to make sure that nothing falls through the cracks.  

The first and the most important thing is when you enter a clinical trial, your team grows. You have a primary physician taking care of you, but he has more help and more support. That helps ensure that the best possible care is delivered for our patients. The second benefit of taking part in clinical trials is that you oftentimes have access to the latest and the greatest.  

For example, in the context of non-melanoma skin cancer that is transplant associated, these provocative approaches that are being tested, immune augmentation of immune suppression with concurrent systemic immunotherapy without causing allograft rejection, this is only available in the context of an NCI, ECTCN funded trial that Dr. Lipson is leading. If you’re not a member of one of the ECTCN sites, you do not have access to this trial. If you’re not a patient that is being seen at one of these sites, you, unfortunately, do not have access to this trial.  

The key thing here is, entering a clinical trial represents the ability, potentially, to get a treatment that potentially could improve cancer and save one’s life without causing allograft rejection. In the context of the RP1 study, you could potentially be getting a drug that doesn’t cause allograft rejection and causes cancer aggression in a significant number of patients, but again, it is not a standard of care agent. 

Entering clinical trials helps you because it allows you access to the latest and the greatest in terms of treatment modalities, but also, it allows you to receive the best possible care. 

Emerging Treatments for Advanced Non-Melanoma Skin Cancer: What’s Showing Promise?

Emerging Treatments for Advanced Non-Melanoma Skin Cancer: What’s Showing Promise? from Patient Empowerment Network on Vimeo.

Advances in research for non-melanoma skin cancers lead to new treatment options. Dr. Diwakar Davar provides an update on emerging therapies and shares advice for staying abreast of the latest news.

Dr. Diwakar Davar is the Clinical Director of the Melanoma and Skin Cancer Program at UPMC Hillman Cancer Center. Learn more about Dr. Davar.

Download Guide

See More from Evolve Non-Melanoma Skin Cancer

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An Expert’s Perspective on Advanced Non-Melanoma Skin Cancer Research

An Expert’s Perspective on Advanced Non-Melanoma Skin Cancer Research

What Are the Potential Benefits of an Advanced Non-Melanoma Skin Cancer Clinical Trial

What Are the Potential Benefits of an Advanced Non-Melanoma Skin Cancer Clinical Trial?

What Is Advanced Non-Melanoma Skin Cancer and How Is It Staged?

What Is Advanced Non-Melanoma Skin Cancer and How Is It Staged?


Transcript:

Katherine:

Dr. Davar, now that we understand approved approaches, can you walk us through ongoing research and developing treatments that patients should know about? 

Dr. Davar:

Yeah. Now, if you think about it, the vast majority of patients with, say, cutaneous squamous cell carcinoma is presenting with large tumors involving the areas of the head and neck region. The average tumor size is approximately 1 to 2 cm.  

There are small groups of patients with much larger tumors and/or tumors with high-risk features. These include tumors that are either anatomically large or 3 cm, 4 cm in size, tumors that involve critical locations, such as the bone, the skull table, the jaw, tumors that are very close proximity to critical structures such as the eye, or tumors involving lift nodes in the neck. 

In these patients, recent work by many groups including ours has demonstrated that perioperative immunotherapy improves outcomes. What is perioperative immunotherapy? In the context of melanoma and lung cancer, giving people immunotherapy before surgery improves patient outcomes. This the same drug that you would normally get after surgery, but giving it before surgery. The very same drug before surgery improves event-free survival.  

It improves the likelihood of cancer not coming back. The primary reason for that is by turning the immune system on even before you take the tumor out, you sensitize the immune system to tumor antigens, you kill more cancer, and you do that while the tumor is present because the immune system acts and recognizes this with the immune therapy acting as a vaccine. This approach has now migrated to non-melanoma skin cancer and is actually transformative, particularly given the location of these tumors which render surgery difficult.  

Therefore, in this disease, not only is perioperative immunotherapy especially transformative in terms in terms of producing dramatic response rates, the median response rate of pathologic perioperative immunotherapy is approximately a path CR rate of approximately 50 percent. In pivotal trials done by Neil Gross, the results of which have been published in prominent journals, neoadjuvant or perioperative cemiplimab (Libtayo), anti-PD-1 inhibitor from Regeneron has shown path response rates of approximately 50 percent. 

Whether it’s given for two cycles over six weeks or four cycles over three months, this drug really dramatically reduces the tumor and improves the likelihood of the cancer not coming back. More interestingly, recent data has also shown that this affects surgical outcomes in other ways. Historically, in melanoma and lung cancer and other diseases where perioperative immunotherapy is a standard of care, we never considered the nature of the surgery. Patients still underwent the same surgery that they would’ve undergone anyway whether or not they got immunotherapy.  

However, given the dramatic effect of perioperative immunotherapy, increasingly, we are turning out attention, particularly in cutaneous squamous cell carcinoma, which involves critical structures, to the role of surgical de-escalation as well as radiation de-escalation.  

We’re trying to see if by using perioperative immunotherapy, you can give people potentially less radical surgery, make people heal faster, undergo less plastic surgical reconstruction, improve functional outcomes, and also reduce the need for radiation, particularly in the patients who have done extraordinarily well to reduce the risk of radiation-related early and long-term toxicity.  

These results, some of which are recently being presented at prominent national meetings by Dr. Zuur from the Dutch NKI as well as Dr. Ascierto from the Italian National Cancer Institute in Naples have shown that firstly, the pathological response rates are high but very provocatively, surgical de-escalation has been achieved and is associated with good quality of life. What we are seeing here is that perioperative immunotherapy really has an increasing role, particularly in this disease, for reasons that have to do with the unique anatomical location of perioperative cutaneous squamous carcinoma.  

Perioperative immunotherapy is also migrating to other non-melanoma skin cancers including Merkel and basal cell carcinoma. Early trials have been done. The drugs appear to be effective. However, trials are still needed to further understand the role of perioperative immunotherapy in these other two entities. However, in cutaneous squamous cell carcinoma, perioperative trials are very advanced, pivotal trials are being designed, and increasingly, this is considered a standard of care for potentially resectable patients.  

You and I have talked about the role of immunocompetent non-melanoma skin cancer but one thing that patients do not necessarily realize that if you have a solid organ transplant such as a liver transplant, a heart transplant, or a kidney transplant, the primary reason for mortality in the first one year is allograft failure. However, if you make it past three years, the primary reason for mortality is cancer, and not cancer of the lung, but primarily, skin cancer. In this instance, the reason that skin cancer is common now, on average, skin cancers in transplant patients are much more common than skin cancer in non-transplant patients.  

In fact, patients with solid organ transplants had 100-fold higher risk of developing skin cancer compared to the general population. It has to do with the immunosuppression that is used. The immune suppression that maintains allograft tolerance also reduces T cell function. 

That reduction in T cell function allows for immune escape and the development of high-risk skin cancers. The most important thing that transplant patients need to do is make sure that they see a dermatologist. Increasingly, as we discover high risk skin cancer, there have been two main approaches that have been identified that are potentially helpful. The first is investigators at two primary sites. One, Dr. Evan Lipson at the Johns Hopkins University and Dr. Glenn Hanna at Mass General Hospital have independently demonstrated, and very provocatively, that in organ transplant patients, very close titration of immunosuppression can be done to allow for the concomitant use of immune modulating therapy.  

Historically, this is a patient population for whom systemic anti-PD-1 immunotherapy was technically contraindicated because the primary risk was allograft failure. What Dr. Hanna and Dr. Lipson have demonstrated is that by carefully modulating the doses of immune suppression, you can co-administer systemic anti PD-1 without allograft rejection, and these transformative results have been publicly represented by Dr. Hanna and Dr. Lipson as a paper under review in a prominent journal.  

Concurrently, work by a biopharmaceutical company known as Replimune has demonstrated that the intralesional administration of an oncolytic virus, a cancer killing virus known as RP1, has provocatively demonstrated anti-cancer effect in high-risk, advanced transplant-associated skin cancers.  

These data have been presented by many colleagues, including myself and others at several recent meetings, and the most recent publication of which was by Dr. Mike Migden of MD Anderson Cancer Center in a recent transplant meeting. This drug, which was injected within the tumor by direct visual injection has dramatic effect in up to about 25 percent of the treated patients without any risk of allograft rejection and/or herpes serial conversion because this is an attenuated herpes virus. These two advances have dramatically altered the potential for patients with solid organ cancers who are developing skin cancers to potentially get novel agents that would otherwise, the absence of which, potentially result in mortality. 

Katherine:

Wow. That’s really exciting news. Research often moves quickly and I think you’re just pointing this out. How can patients stay up to date with what’s going on?  

Dr. Davar:

Well, it’s very difficult. The information is moving at the speed of light in this disease. In fact, the first study of perioperative immunotherapy was done two years ago. Right now, perioperative immunotherapy is on NCCN guidelines. 

It’s not FDA-approved, but it’s a strong Class One recommendation on NCCN given the dramatic data that Dr. Gross and many of our colleagues have generated. Just in the span of three years, much has been achieved. The way to stay up to date is to read and also to seek out information from well-trusted sources. Information such as what has been generated by the Health Content Collective, information that is from WebMD and these other areas are very useful, but do check in with your providers. Please make sure your providers are up to date and do not be afraid of asking questions. No provider would ever feel insulted that you are questioning his or her judgment by asking a question.  

I often welcome patients to ask me questions about whether or not I feel like this is the best therapeutic modality, and do ask if there is a role for novel treatments. This is particularly because when you advance, as I mentioned, at the speed of light, particularly in the context of patients who are immunosuppressed… 

Treatment Options for Advanced Non-Melanoma Skin Cancer

Treatment Options for Advanced Non-Melanoma Skin Cancer from Patient Empowerment Network on Vimeo.

Treatment options for advanced non-melanoma skin cancers are ever-changing. Dr. Diwakar Davar reviews current treatment options and discusses which medical professionals are involved in treating advanced non-melanoma skin cancers.

Dr. Diwakar Davar is the Clinical Director of the Melanoma and Skin Cancer Program at UPMC Hillman Cancer Center. Learn more about Dr. Davar.

Download Guide

See More from Evolve Non-Melanoma Skin Cancer

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An Expert’s Perspective on Advanced Non-Melanoma Skin Cancer Research

An Expert’s Perspective on Advanced Non-Melanoma Skin Cancer Research

What Are the Potential Benefits of an Advanced Non-Melanoma Skin Cancer Clinical Trial

What Are the Potential Benefits of an Advanced Non-Melanoma Skin Cancer Clinical Trial?

Emerging Treatments for Advanced Non-Melanoma Skin Cancer: What’s Showing Promise

Emerging Treatments for Advanced Non-Melanoma Skin Cancer: What’s Showing Promise?


Transcript:

Katherine:

What approaches are currently available to treat these more common forms of advanced non-melanoma skin cancer? 

Dr. Davar:

Right now, the most common mode of treatment is typically treating cancer that is localized.  

Again, even with the extremely increasing incidence of these cancers, the vast majority of cancers that we detect are still localized and are amenable to easy surgical eradication by a trained dermatologist or a trained mole surgeon. A trained dermatologist, a trained mole surgeon, a plastic surgeon, these are commonly the physicians that encounter these patients. Surgical removal is still the primary mode of eradications of these lesions. However, increasingly, there is a role for early systemic therapy and local regional therapy to improve patient outcomes for reasons that we can talk about. Still, the vast majority of patients are still treated surgically and then increasingly, there is the role for referral to medical oncologists and radiation oncologists to talk about alternative forms of treatment that may be needed after that. 

Katherine:

What sort of alternative therapies? Are you looking at targeted therapies? Immunotherapies? 

Dr. Davar:

The primary reason for which advances have happened in this disease is really the advent of effective systemic immunotherapy and the spillover of immunotherapy into the patient landscape in these diseases. The reason for that is as follows. Immunotherapy essentially is most effective in tumors that carry a high tumor mutation burden. For example, melanoma has a tumor mutation burden on average of about 15, and the tumor mutation burden in melanoma is driven by the fact that melanoma, cutaneous melanoma is an ultraviolet light-driven skin cancer.  

However, non-melanoma skin cancers have tumor mutation burdens that are many, many magnitudes higher than that of melanoma. For example, the median tumor mutation burden in cutaneous squamous cell carcinoma is 50. Melanoma is 15. The median tumor mutation burden in cutaneous squamous cell carcinoma is three times that of melanoma. Similarly, for Merkel cell carcinoma. A large majority of Merkel cell carcinoma is caused by an unusual virus known as a Merkel cell polyomavirus. Both the viral driven tumors and the non-viral driven tumors have high tumor mutation burdens, and the same is true of basal cell carcinoma because of ultraviolet light exposure.  

The primary reason why immunotherapy has gotten a foothold in these diseases is because the underlying etiologic agent that drives carcinogenesis, ultraviolet light for the majority of these, and the Merkel cell polyomavirus for the subcategory of non-melanoma skin cancer that is Merkel are both associated with a response to immunotherapy.   

As a result of that, immunotherapy, anti-PD-1 immunotherapy is now standard of care for patients with tumors that are either locally advanced undissectible or locally advanced and/or metastatic, that is, that they have spread. They are now available for use and FDA-approved for this indication in both Merkel, basal, as well as non-melanoma cutaneous squamous cell carcinoma. 

What Is Advanced Non-Melanoma Skin Cancer and How Is It Staged?

What Is Advanced Non-Melanoma Skin Cancer and How Is It Staged? from Patient Empowerment Network on Vimeo.

Dr. Advanced non-melanoma skin cancer encompasses several skin cancer types. Dr. Diwakar Davar discusses the most common types of advanced non-melanoma skin cancer and factors involved in staging.

Dr. Diwakar Davar is the Clinical Director of the Melanoma and Skin Cancer Program at UPMC Hillman Cancer Center. Learn more about Dr. Davar.

Download Guide

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Treatment Options for Advanced Non-Melanoma Skin Cancer

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Emerging Treatments for Advanced Non-Melanoma Skin Cancer: What’s Showing Promise

Emerging Treatments for Advanced Non-Melanoma Skin Cancer: What’s Showing Promise?


Transcript:

Katherine:

Today, we’re focusing on the most common forms of advanced non-melanoma skin cancer. What does it mean to have advanced non-melanoma skin cancer? 

Dr. Davar:

Sure. “Non-melanoma skin cancer” is actually a very broad, heterogenous term and includes patients with cutaneous squamous cell carcinoma, which is actually the commonest cancer in the United States with approximately 1 million cases a year, the vast majority of which are actually not necessarily, particularly serious or deep but do indicate predisposition towards further cancers and exposure to carcinogenic ultraviolet light. 

 It also includes the entities of Merkel cell carcinoma as well as basal cell carcinoma. These common cancers ranging from very common cutaneous squamous cell carcinoma to the least common Merkel cell carcinoma and basal cell in between are primarily seen in Caucasian patients. There is a predisposition towards these cancers we discovered in patients who are older, and certainly there is a predisposition in finding these cancers in certain anatomical regions such as the head and neck areas. Most of these cancers happen in older Caucasian patients, typically above the clavicle in the head, neck, around the ears, and on the cheeks and the face. 

Katherine:

Why is that?  

Dr. Davar:

Well, the primary etiologic agent driving carcinogenesis in these cancers is ultraviolet light.  

Again, the vast majority of ultraviolet light exposure happens to people before the age of 12, and it happens predominantly on the head and neck because that is the area that is most exposed to the sun. The cancer takes a while to form because the carcinogenic effects take a while to cause the cancer. So predominantly, patients, as they start hitting their 70s and 80s, it becomes increasingly common and occasionally, these cancers can actually end up being serious and start causing advanced cancers.  

Katherine:

What does it mean to have advanced non-melanoma skin cancer? 

Dr. Davar:

You know, in most cases, the definition of what is considered an advanced cancer is stage IV disease. If you have lung cancer, advanced lung cancer is stage IV cancer that has spread to the opposite lung, or to the brain, or the liver. 

If you have advanced melanoma, it is cancer that has spread to a distant organ such as the lung, the liver, or the brain. Skin cancer is very, very different. Because of its unique anatomical location, even a large tumor that potentially can be cut out but hasn’t necessarily spread can still threaten vital organs. You can have a 3 cm tumor near the eye that is threatening the globe. If it is not shrunk, the surgical resection of this tumor will potentially involve removing the eye.  

Similarly, you can have a very large tumor that is not necessarily spread, but is involving the right side of the cheek near the jaw in which case, the potential surgical removal of this tumor would involve the extremely disfiguring surgery of jaw removal, what is known as mandibulectomy.  

Given the nature of these tumors and the location of these tumors, the definition of locally advanced for this particular cancer has started to incorporate more elements of the location and the ease of which the cancer can be removed, which is very distinct from cancers in other locations, and also the proximity of these cancers to critical structures such as the nose, the lips, the eye, as well as critical vascular and neurovascular structures in the neck, such as the carotid artery, the internal and external jugular veins, and the vagal nerve bundle. 

Advanced Non-Melanoma Skin Cancer: What Do You Need to Know About Evolving Treatment and Research

Advanced Non-Melanoma Skin Cancer: What Do You Need to Know About Evolving Treatment and Research? from Patient Empowerment Network on Vimeo.

Treatment options for advanced non-melanoma skin cancers—such as squamous and basal cell carcinoma—are evolving quickly. Dr. Diwakar Davar shares an update on emerging research, discusses current treatment options, and provides tips for partnering with your team on care decisions.

Dr. Diwakar Davar is the Clinical Director of the Melanoma and Skin Cancer Program at UPMC Hillman Cancer Center. Learn more about Dr. Davar.

Download Guide

See More from Evolve Non-Melanoma Skin Cancer

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An Expert’s Perspective on Advanced Non-Melanoma Skin Cancer Research

An Expert’s Perspective on Advanced Non-Melanoma Skin Cancer Research

Expert Advice for Newly Diagnosed Advanced Non-Melanoma Skin Cancer Patients

Expert Advice for Newly Diagnosed Advanced Non-Melanoma Skin Cancer Patients

Advanced Non-Melanoma Skin Cancer: Who Is on Your Healthcare Team?

Advanced Non-Melanoma Skin Cancer: Who Is On Your Healthcare Team?


Transcript:

Katherine:

Hello, and welcome. I’m your host, Katherine Banwell. Today’s program focuses on helping patients with advanced non-melanoma skin cancer. We’ll review treatments, and research, and share advice for getting involved in care decisions. Before we meet our guest, let’s review a few important details. The reminder email you received about this program contains a link to a program resource guide. If you haven’t already, click that link to access information to follow along during the webinar.  

At the end of this program, you’ll receive a link to a program survey. Please take a moment to provide feedback about your experience today in order to help us plan future webinars. Finally, before we get into the discussion, please remember that this program is not a substitute for seeking medical advice.  

Please refer to your healthcare team about what might be best for you. Let’s meet our guest today. Joining me is Dr. Diwakar Davar. Dr. Davar, welcome. Would you please introduce yourself? 

Dr. Davar:

Katherine, thank you for this invitation. My name is Diwakar. I’m a medical oncologist and I’m the Clinical Director of Cutaneous Malignancies and Melanoma at the University of Pittsburgh’s Hillman Cancer Center. My practice largely focuses on advanced skin cancer, including both melanoma and non-melanoma skin cancers. I also direct the translational research laboratory focusing on drug development. I’m glad to be able to contribute towards this program. And, I’m happy to answer any questions that you and your colleagues might have. 

Katherine:

Well, thank you so much for taking time out of your schedule to join us today. 

Dr. Davar:

Sure. 

Katherine:

Today, we’re focusing on the most common forms of advanced non-melanoma skin cancer. What does it mean to have advanced non-melanoma skin cancer? 

Dr. Davar:

Sure. “Non-melanoma skin cancer” is actually a very broad, heterogenous term and includes patients with cutaneous squamous cell carcinoma, which is actually the commonest cancer in the United States with approximately 1 million cases a year, the vast majority of which are actually not necessarily, particularly serious or deep but do indicate predisposition towards further cancers and exposure to carcinogenic ultraviolet light. 

It also includes the entities of Merkel cell carcinoma as well as basal cell carcinoma. These common cancers ranging from very common cutaneous squamous cell carcinoma to the least common Merkel cell carcinoma and basal cell in between are primarily seen in Caucasian patients. There is a predisposition towards these cancers we discovered in patients who are older, and certainly there is a predisposition in finding these cancers in certain anatomical regions such as the head and neck areas. Most of these cancers happen in older Caucasian patients, typically above the clavicle in the head, neck, around the ears, and on the cheeks and the face. 

Katherine:

Why is that?  

Dr. Davar:

Well, the primary etiologic agent driving carcinogenesis in these cancers is ultraviolet light.  

Again, the vast majority of ultraviolet light exposure happens to people before the age of 12, and it happens predominantly on the head and neck because that is the area that is most exposed to the sun. The cancer takes a while to form because the carcinogenic effects take a while to cause the cancer. So predominantly, patients, as they start hitting their 70s and 80s, it becomes increasingly common and occasionally, these cancers can actually end up being serious and start causing advanced cancers.  

Dr. Davar:

You know, in most cases, the definition of what is considered an advanced cancer is stage IV disease. If you have lung cancer, advanced lung cancer is stage IV cancer that has spread to the opposite lung, or to the brain, or the liver. 

If you have advanced melanoma, it is cancer that has spread to a distant organ such as the lung, the liver, or the brain. Skin cancer is very, very different. Because of its unique anatomical location, even a large tumor that potentially can be cut out but hasn’t necessarily spread can still threaten vital organs. You can have a 3 cm tumor near the eye that is threatening the globe. If it is not shrunk, the surgical resection of this tumor will potentially involve removing the eye.   

Similarly, you can have a very large tumor that is not necessarily spread, but is involving the right side of the cheek near the jaw. In which case, the potential surgical removal of this tumor would involve the extremely disfiguring surgery of jaw removal, what is known as mandibulectomy.   

Given the nature of these tumors and the location of these tumors, the definition of locally advanced for this particular cancer has started to incorporate more elements of the location and the ease of which the cancer can be removed, which is very distinct from cancers in other locations, and also the proximity of these cancers to critical structures such as the nose, the lips, the eye, as well as critical vascular and neurovascular structures in the neck, such as the carotid artery, the internal and external jugular veins, and the vagal nerve bundle. 

Katherine:

What approaches are currently available to treat these more common forms of advanced non-melanoma skin cancer? 

Dr. Davar:

Right now, the most common mode of treatment is typically treating cancer that is localized.  

Again, even with the extremely increasing incident of these cancers, the vast majority of cancers that we detect are still localized and are amenable to easy surgical eradication by a trained dermatologist or a trained mole surgeon. A trained dermatologist, a trained mole surgeon, a plastic surgeon, these are commonly the physicians that encounter these patients. Surgical removal is still the primary mode of eradications of these lesions. However, increasingly, there is a role for early systemic therapy and local regional therapy to improve patient outcomes for reasons that we can talk about. Still, the vast majority of patients are still treated surgically and then increasingly, there is the role for referral to medical oncologists and radiation oncologists to talk about alternative forms of treatment that may be needed after that. 

Katherine:

What sort of alternative therapies? Are you looking at targeted therapies? Immunotherapies?  

Dr. Davar:

The primary reason for which advances have happened in this disease is really the advent of effective systemic immunotherapy and the spillover of immunotherapy into the patient landscape in these diseases. The reason for that is as follows. Immunotherapy essentially is most effective in tumors that carry a high tumor mutation burden. For example, melanoma has a tumor mutation burden on average of about 15. And the tumor mutation burden in melanoma is driven by the fact that melanoma, cutaneous melanoma is an ultraviolet light-driven skin cancer.  

However, non-melanoma skin cancers have tumor mutation burdens that are many, many magnitudes higher than that of melanoma. For example, the median tumor mutation burden in cutaneous squamous cell carcinoma is 50. Melanoma is 15. The median tumor mutation burden in cutaneous squamous cell carcinoma is three times that of melanoma. Similarly, for Merkel cell carcinoma. A large majority of Merkel cell carcinoma is caused by an unusual virus known as a Merkel cell polyomavirus. Both the viral driven tumors and the non-viral driven tumors have high tumor mutation burdens, and the same is true of basal cell carcinoma because of ultraviolet light exposure.  

The primary reason why immunotherapy has gotten a foothold in these diseases is because the underlying etiologic agent that drives carcinogenesis, ultraviolet light for the majority of these, and the Merkel cell polyomavirus for the subcategory of non-melanoma skin cancer that is Merkel are both associated with a response to immunotherapy.  

As a result of that, immunotherapy, anti-PD-1 immunotherapy is now standard of care for patients with tumors that are either locally advanced undissectible or locally advanced and/or metastatic, that is, that they have spread. They are now available for use and FDA-approved for this indication in both Merkel, basal, as well as non-melanoma cutaneous squamous cell carcinoma. 

Katherine:

Dr. Davar, now that we understand approved approaches, can you walk us through ongoing research and developing treatments that patients should know about? 

Dr. Davar:

Yeah. Now, if you think about it, the vast majority of patients with, say, cutaneous squamous cell carcinoma is presenting with large tumors involving the areas of the head and neck region. The average tumor size is approximately 1 to 2 cm.  

There are small groups of patients with much larger tumors and/or tumors with high-risk features. These include tumors that are either anatomically large or 3 cm, 4 cm in size, tumors that involve critical locations, such as the bone, the skull table, the jaw, tumors that are very close proximity to critical structures such as the eye, or tumors involving lift nodes in the neck. 

In these patients, recent work by many groups including ours has demonstrated that perioperative immunotherapy improves outcomes. What is perioperative immunotherapy? In the context of melanoma and lung cancer, giving people immunotherapy before surgery improves patient outcomes. This the same drug that you would normally get after surgery, but giving it before surgery. The very same drug before surgery improves event-free survival.  

It improves the likelihood of cancer not coming back. The primary reason for that is by turning the immune system on even before you take the tumor out, you sensitize the immune system to tumor antigens, you kill more cancer, and you do that while the tumor is present because the immune system acts and recognizes this with the immune therapy acting as a vaccine. This approach has now migrated to non-melanoma skin cancer and is actually transformative, particularly given the location of these tumors which render surgery difficult.   

Therefore, in this disease, not only is perioperative immunotherapy especially transformative in terms in terms of producing dramatic response rates, the median response rate of pathologic perioperative immunotherapy is approximately a path CR rate of approximately 50 percent. In pivotal trials done by Neil Gross, the results of which have been published in prominent journals, neoadjuvant or perioperative Cemiplimab, anti-PD-1 inhibitor has shown path response rates of approximately 50 percent. 

Whether it’s given for two cycles over six weeks or four cycles over three months, this drug really dramatically reduces the tumor and improves the likelihood of the cancer not coming back. More interestingly, recent data has also shown that this affects surgical outcomes in other ways. Historically, in melanoma and lung cancer and other diseases where perioperative immunotherapy is a standard of care, we never considered the nature of the surgery. Patients still underwent the same surgery that they would’ve undergone anyway whether or not they got immunotherapy.  

However, given the dramatic effect of perioperative immunotherapy, increasingly, we are turning out attention, particularly in cutaneous squamous cell carcinoma, which involves critical structures, to the role of surgical de-escalation as well as radiation de-escalation.  

We’re trying to see if by using perioperative immunotherapy, you can give people potentially less radical surgery, make people heal faster, undergo less plastic surgical reconstruction, improve functional outcomes, and also reduce the need for radiation, particularly in the patients who have done extraordinarily well to reduce the risk of radiation-related early and long-term toxicity.  

These results, some of which are recently being presented at prominent national meetings by Dr. Zuur from the Dutch NKI. As well as Dr. Ascierto from the Italian National Cancer Institute in Naples have shown that firstly, the pathological response rates are high but very provocatively, surgical de-escalation has been achieved and is associated with good quality of life. What we are seeing here is that perioperative immunotherapy really has an increasing role. Particularly in this disease, for reasons that have to do with the unique anatomical location of perioperative cutaneous squamous carcinoma.  

Perioperative immunotherapy is also migrating to other non-melanoma skin cancers including Merkel and basal cell carcinoma. Early trials have been done. The drugs appear to be effective. However, trials are still needed to further understand the role of perioperative immunotherapy in these other two entities. However, in cutaneous squamous cell carcinoma, perioperative trials are very advanced, pivotal trials are being designed, and increasingly, this is considered a standard of care for potentially resectable patients.  

You and I have talked about the role of immunocompetent non-melanoma skin cancer but one thing that patients do not necessarily realize that if you have a solid organ transplant such as a liver transplant, a heart transplant, or a kidney transplant, the primary reason for mortality in the first one year is allograft failure. However, if you make it past three years, the primary reason for mortality is cancer, and not cancer of the lung, but primarily, skin cancer. In this instance, the reason that skin cancer is common now, on average, skin cancers in transplant patients are much more common than skin cancer in non-transplant patients.  

In fact, patients with solid organ transplants had 100-fold higher risk of developing skin cancer compared to the general population. It has to do with the immunosuppression that is used. The immune suppression that maintains allograft tolerance also reduces T cell function. 

That reduction in T cell function allows for immune escape and the development of high-risk skin cancers. The most important thing that transplant patients need to do is make sure that they see a dermatologist. Increasingly, as we discover high risk skin cancer, there have been two main approaches that have been identified that are potentially helpful. The first is investigators at two primary sites. One, Dr. Evan Lipson at the Johns Hopkins University and Dr. Glenn Hanna at Mass General Hospital have independently demonstrated, and very provocatively, that in organ transplant patients, very close titration of immunosuppression can be done to allow for the concomitant use of immune modulating therapy.  

Historically, this is a patient population for whom systemic anti PD-1 immunotherapy was technically contraindicated because the primary risk was allograft failure. What Dr. Hanna and Dr. Lipson have demonstrated is that by carefully modulating the doses of immune suppression, you can co-administer systemic anti PD-1 without allograft rejection, and these transformative results have been publicly represented by Dr. Hanna and Dr. Lipson as a paper under review in a prominent journal.  

Concurrently, work by a biopharmaceutical company has demonstrated that the intralesional administration of an oncolytic virus, a cancer killing virus known as RP1, has provocatively demonstrated anti-cancer effect in high-risk, advanced transplant-associated skin cancers.  

These data have been presented by many colleagues, including myself and others at several recent meetings. And the most recent publication of which was by Dr. Mike Migden of MD Anderson Cancer Center in a recent transplant meeting. This drug, which was injected within the tumor by direct visual injection has dramatic effect in up to about 25 percent of the treated patients without any risk of allograft rejection and/or herpes serial conversion because this is an attenuated herpes virus. These two advances have dramatically altered the potential for patients with solid organ cancers who are developing skin cancers to potentially get novel agents that would otherwise, the absence of which, potentially result in mortality. 

Katherine:

Wow. That’s really exciting news. Research often moves quickly and I think you’re just pointing this out. How can patients stay up to date with what’s going on? 

Dr. Davar:

Well, it’s very difficult. The information is moving at the speed of light in this disease. In fact, the first study of perioperative immunotherapy was done two years ago. Right now, perioperative immunotherapy is on NCCN guidelines. 

It’s not FDA-approved, but it’s a strong Class One recommendation on NCCN given the dramatic data that Dr. Gross and many of our colleagues have generated. Just in the span of three years, much has been achieved. The way to stay up to date is to read and also to seek out information from well-trusted sources. Information such as what has been generated by the Health Content Collective, information that is from WebMD and these other areas are very useful, but do check in with your providers. Please make sure your providers are up to date and do not be afraid of asking questions. No provider would ever feel insulted that you are questioning his or her judgment by asking a question.  

I often welcome patients to ask me questions about whether or not I feel like this is the best therapeutic modality. And, do ask if there is a role for novel treatments. This is particularly because when you advance, as I mentioned, at the speed of light, particularly in the context of patients who are immunosuppressed.

Katherine:

Dr. Davar, thank you for that detailed information. It is really valuable. You mentioned, a few moments ago, clinical trials. What are the benefits of participating in a clinical trial? 

Dr. Davar:

Well, the first and the most important benefit of participating in a clinical trial is that oftentimes, your team is larger. Normally, a patient has a doctor. We have a PA and we have a nurse taking care of them. When you have a clinical trial, at that clinical trial, you have three, four, five times that number of people taking care of you. There are research nurses, research coordinators, nurse navigators, and all of these people are looking over your chart helping the doctor cross check and check to make sure that nothing falls through the cracks.  

The first and the most important thing is when you enter a clinical trial, your team grows. You have a primary physician taking care of you, but he has more help and more support. That helps ensure that the best possible care is delivered for our patients. The second benefit of taking part in clinical trials is that you oftentimes have access to the latest and the greatest.  

For example, in the context of non-melanoma skin cancer that is transplant associated, these provocative approaches that are being tested, immune augmentation of immune suppression with concurrent systemic immunotherapy without causing allograft rejection, this is only available in the context of an NCI, ECTCN funded trial that Dr. Lipson is leading. If you’re not a member of one of the ECTCN sites, you do not have access to this trial. If you’re not a patient that is being seen at one of these sites, you, unfortunately, do not have access to this trial.  

The key thing here is, entering a clinical trial represents the ability, potentially, to get a treatment that potentially could improve cancer and save one’s life without causing allograft rejection. In the context of the RP1 study, you could potentially be getting a drug that doesn’t cause allograft rejection and causes cancer aggression in a significant number of patients. But again, it is not a standard of care agent. 

Entering clinical trials helps you because it allows you access to the latest and the greatest in terms of treatment modalities. But also, it allows you to receive the best possible care.  

Katherine:

You know, Dr. Davar, we often hear this term “personalized medicine.” What does it mean? 

Dr. Davar:

Personalized medicine really means individualizing the patient’s treatment for that particular patient’s tumor. No two tumors are the same. Every tumor is different just as every person is different. Therefore, identifying and crafting the optimal treatment plan really involves identifying the most available and up-to-date information about the person’s tumor and contextualizing the treatment options in that setting.  

For example, in the context of Merkel cell polyoma, the virus associated with Merkel cell carcinoma, the treatment options would certainly include checkpoint inhibitor therapy with the understanding that the Merkel cell polyomavirus status could change both the response to the treatment but also the monitoring of the treatment because there is and acid that uses antibody titers to track the disease.  

In the context of patients with advanced cutaneous squamous cell carcinoma, the presence or absence of intratumoral CD8 T cells very provocatively can affect the response of checkpoint inhibitor therapy. The key thing to understand about personalized medicine is the more information we have about your tumor, the more informed we are about not only your current treatment, but also what future treatments might be available to you if the current treatment stops working. 

Katherine:

Aside from testing, what other factors are involved when choosing therapy? 

Dr. Davar:

These factors include, particularly for non-melanoma skin cancers, the patient’s age and performance status. We do know that as patients get older, their comorbid piece changes. They have a higher risk of having concomitant second illness such as cardiac issues, diabetes, high blood pressure, cholesterol issues, strokes, and coronary artery disease.  

These diseases in and of themselves do not necessarily affect one treatment choice over another, but it may change how you treat the patient. For example, a 60-year-old patient with melanoma may be a great surgical candidate. A 60-year-old patient with squamous cell carcinoma maybe a great surgical candidate. However, an 85-year-old patient with cutaneous squamous cell carcinoma with a tumor near the eye may not necessarily be a great surgical candidate because even though the tumor could be removed, it would result in the removal of that person’s eye.  

If this person has already has got, for example, age-related issues with balance, age-related issues with difficulty and vision and depth perception, removing this person’s eye, which is a very morbid procedure, but can be done at relatively low surgical risk, could really affect this patient’s quality of life and may force you to rethink what you would do and may result in you offering this patient a different treatment modality such as upfront use of systemic therapy rather than a standard surgical approach.  

The idea is that the more information you have about the patient, the easier it is to contextualize the treatment for a particular patient and particularly in the context of non-melanoma skin cancer. Which often time happens to patients who are, on average, one decade older than patients with melanoma. Taking their age and taking their comorbid conditions is very important in determining the treatment modality and also in making individualized patient recommendations. 

Katherine:

It’s not always easy to access the latest treatments or to find a specialist. I’m wondering what the common obstacles patients face in accessing the best care.  

Dr. Davar:

Some of the major issues are access to highly specialized treatment centers. Across the entire United States, there are clearly comprehensive cancer centers where the NCIS designated these places as being areas where patient care can deliver clinical trials available.  

Oftentimes, there is the breadth of research all the way from population research all the way to clinical trials. Not everybody has access to a comprehensive cancer center. Some patients may be living in a geographical location that is remote. Some patients could be living in a location that is not necessarily remote from a comprehensive cancer center, but may have social determinants of health that make it hard for them to access these comprehensive cancer centers. The only way around this is information.  

Patients need to be able to access information in a fashion that is both trusted, and up-to-date, and secure so that they are enabled and equipped with the right information for them to be able to have informed discussions about their care with their providers. 

Katherine:

This is all such great information, Dr. Davar. As we wrap up, I would like to get your thoughts.  

How do you feel about the future of advanced non-melanoma skin cancer research? 

Dr. Davar:

I am actually extraordinary optimistic about this landscape. When I started out as an oncologist, my big focus was in melanoma. I very quickly realized that most of the excitement was certainly, while in melanoma, was being generated, it was actually spilling over into non-melanoma skin cancer and the primary reason for that is the unique patient level challenges that make this disease a difficult disease to treat. The patient age, the comorbidities, the fact that a vast majority of our patients had gotten transplants, and that resulted in a relative contraindication of the administration of the effective agents that were developed that eradicated the majority of this disease.   

What oftentimes is a challenge, what is one man’s challenge is another man’s potential cure and it’s a potential benefit in an area in which it could be studied.  

What we realize about these challenges is they actually give us opportunities and avenues for research. As we think about non-melanoma skin cancer, we realize that this is an area in which there is tremendous potential where you can potentially give people immune therapy and improved outcomes, but not just improve patient outcomes in making people live longer, but also by reducing the burden of care by reducing the amount of surgery and radiation that people need that enables people to not just live longer, but live longer and maintain their quality of life as they age, and allows them to age with dignity. 

Katherine:

Dr. Davar, it all sounds so exciting. I want to thank you for taking the time to join us today. 

Dr. Davar:

Well, thank you for having me on this lovely program. 

Katherine:

And, thank you to all of our collaborators. If you would like to watch this webinar again, there will be a replay available soon. You’ll receive an email when it’s ready. Don’t forget to take the survey immediately following this webinar. It will help us as we plan future programs.  

To learn more about advanced non-melanoma skin cancer, and to access tools to help you become a proactive patient, visit powerfulpatients.org. I’m Katherine Banwell. Thanks for joining us today.  

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