Cutaneous Squamous Cell Carcinoma: What Is Immunotherapy?



Todd E. Schlesinger, M.D., FAAD: Let’s talk about immunotherapy. Immunotherapy is a new paradigm in oncology. Before we used chemotherapy, which pretty much destroys all the cells that it gets ahold of, so it’s not very efficient, but it covers a wide area. You can also use targeted therapies, which target either certain cells or certain tissues. That has not been approved yet for squamous cell carcinoma. But what we’ve seen lately is the rise of immunotherapy.

Now what immunotherapy does is it helps the body uncloak tumors. If you think of it this way, as the body trains itself, as it trains its immune system to protect itself from tumors, it also trains itself to protect itself from attacking its own cells. It’s called protection against self-immunity, going after one cell. There are receptors that are on the surface of the cells, tumor cells and also normal cells, that tell the T-cells in your body, which can attack tumors, to leave them alone. So it can help protect normal cells, and tumors have evolved ways of exhibiting these receptors on their surface as well so they can also tell the T-cells to leave them alone.

And what immunotherapy does is it blocks the interactions between the receptors on the tumors and the receptors on the T-cells. So the T-cells now no longer see that tumor as cloaked, which it uncloaks the tumor, and now the T-cells attack the tumor. That’s basically what’s going on with immunotherapy in a nutshell. Those interactions can occur in different places. They can occur in the tumor bed itself, what we call the tumor microenvironment. They can also occur in the lymph nodes, and in other places: almost every cell in the body exhibits to some extent these receptors.

Around about 2013, 2014 or 2015, we saw a rise in immunotherapeutic medications for different cancers. Some of them are being used for the head and neck communities, squamous cell carcinomas of the head and neck. Pembrolizumab, nivolumab and also cetuximab are different immunotherapies that have been used for head and neck squamous cell carcinoma. But in the past few years more and more research has been done with a medication called cemiplimab. Now cemiplimab is what we call a PD-1 [programmed cell death protein 1] inhibitor. I mentioned those receptors. There are PD-1 receptors on the surface of T-cells and PD-L1 [programmed death-ligand 1] receptors on the surface of tumor cells. And so if you block the interactions, the T-cells will attack the tumor cells more efficiently.

The most recent agent that was approved was cemiplimab, and that drug was approved in 2018. Toward the end of 2018 that drug was approved for use in advanced squamous cell carcinoma, and what we mean by advanced is the disease is locally advanced or metastatic. And the types of patients that the medication is used for are patients with locally advanced or metastatic squamous cell carcinoma. They’re not candidates for curative surgery or curative radiation.

How is immunotherapy different from chemotherapy? I would say it’s more of an efficiency. Chemotherapy is more targeted therapy. It uncloaks the tumor cells, and the tumor cells that have more inflammation—like squamous cell carcinomas, they tend to have more inflammatory cells within them—are better targets for immunotherapy.

Now immunotherapy does not destroy all cells in the nature that chemotherapy will. But it can have adverse effects on almost every organ system in the body because you are waking up the immune system not only in the tumor but also in any organ system. So unlike chemotherapy, you don’t lose your hair with immunotherapy, but you can still have effects on your lungs, your kidneys, your colon or your skin. Those are the main side effects that we see. It can also affect your endocrine system, which is your thyroid gland, and other glands can be affected as well. Pretty much almost any systems can be affected by the drug as far as adverse effect goes. But luckily the adverse effects that we’re seeing with the newer immunotherapy agents are lower than we’ve seen in some of the older agents, and certainly in a general sense lower than in chemotherapy. I would say the best way to describe them is they’re more efficient. You have better outcome with fewer adverse effects.

How do we manage our patients’ expectations with immunotherapy? It really depends a lot on what type of tumor they have. But what we can tell patients in a general sense in comparing that to chemotherapy is that we can expect better outcomes. The studies show that immunotherapy has a higher likelihood of attaining a response, either a partial or complete response, than most chemotherapies. We can also describe clearly the adverse effects and more how to manage them.

Patients can sometimes start to see tumor shrinkage with the first or even the second dose of immunotherapy. With cemiplimab, the agent that’s approved by the FDA [Food and Drug Administration] now for treatment of locally advanced or metastatic squamous cell carcinoma, you can see response as soon as two months, and sometimes it can take four or five months, depending on the tumor. The metastatic tumors actually respond more quickly than the locally advanced tumors. For whatever reason that seems to be the case so far.

Oftentimes within the first few months patients can start seeing benefit. After the first two or three doses they also may start seeing some of the adverse effects as well, and depending on how severe they are, that would help us guide how to manage those as well. Do we need to stop the drug and give them a break from that? Can we continue with the drug and just manage the side effects? Or do we need to stop the drug completely and not restart it? It really depends on how severe the adverse effects are and whether we can get them back under control easily.

How do we decide when a patient’s eligible for immunotherapy? What we’re looking for is to determine if a patient is a candidate for curative surgery or curative radiation. That decision usually takes place in what’s called a multidisciplinary team where several physicians are involved. Maybe an oncologist, maybe a Mohs surgeon, maybe a radiation oncologist, maybe a head and neck surgeon, and maybe a patient advocate or someone who can explain to the patient in even more detail or be on their side as far as navigating care for the patient is oftentimes involved and on the team as well.

Transcript Edited for Clarity

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