Choosing Systemic Therapies for Patients with Unresectable or Metastatic CSCC

Transcript:

Sunandana Chandra, MD, MS: Dr Pavlick, when a person with unresectable or metastatic cutaneous squamous cell carcinoma walks into your office, can you run through the rationale and the patient and disease characteristics that help you decide what systemic therapy to choose? Go a little into detail with respect to how those therapies are administered, what you expect, etc.

Anna C. Pavlick, DO: We’re talking about patients who’ve been referred because they have been radiated and now have a recurrence, or radiation is not an option, or surgery can be done but may be disfiguring. Patients say, “We don’t want to undergo surgery,” or “I don’t have transportation to get to radiation every day.” Those patients get referred to medical oncology. Keeping those things in mind and knowing that’s why the patients are showing up in our office, the biggest thing we have to look at is their medical history. Do they have confounding medical problems that are going to prohibit them or make them more at risk of toxicity from our therapies? We talked about solid organ transplants and organ rejection if we use an anti PD-1 therapy.

One other thing we also need to consider is that some of our therapies will include capsules. [Some] patients cannot swallow capsules. These medicines aren’t things that we can open or crush or put through a feeding tube, so that may not be a viable option for those patients. We need to look at their overall performance status and how they function. Are they in a nursing home? Do they live on their own? Do they have the psychosocial support that they need to undergo therapy, whether it’s pills every day or infusions every 3 weeks?

When it comes to cutaneous squamous cell carcinoma, they’re in our offices because they have refused [surgery], progressed through radiation, or aren’t candidates for or don’t want surgery. Some of the things we need to talk to them about are anti–PD-1 agents. We have several therapies approved for locally advanced or metastatic squamous cell carcinoma. The 2 agents we most commonly use in this disease are cemiplimab and pembrolizumab. Both have the potential toxicities of rash and pruritus. Some patients, if they have underlying GI [gastrointestinal] disorders like Crohn's disease or ulcerative colitis, may be more prone to developing inflammatory diarrhea from these agents. You can also get pneumonitis or autoimmune-induced hepatitis from the drugs. One thing that we don’t tell patients that often is that they need to report visual changes because these drugs can also cause uveitis, which needs to be assessed by an ophthalmologist.

We’re very familiar with how to manage these toxicities, and we know that corticosteroids are our frontline management for these toxicities. We need to be very honest with patients that although the risk of toxicity is low, they need to be well versed on reporting to us and telling us the adverse effects they’re having. The sooner we intervene, the easier it is to manage these toxicities and allow patients to continue on therapy.

Immunotherapies are very similar to what we use with melanoma. It’s the same toxicity profile. Whether you use a single agent or dual-immunotherapy drugs, you’ll have autoimmune toxicities that you need to deal with. One thing I like to stress to patients is that there’s a low but very real risk of endocrinopathies, for the simple reason that most of the toxicities incurred with immunotherapy are easily manageable and reversible with corticosteroid intervention. When it comes to endocrinopathies, however, if the patient develops hypothyroidism as a consequence of an autoimmune response to immunotherapy, that hypothyroidism is permanent in the majority of cases. Those patients would then be committed to taking thyroid replacement medicine for the rest of their life. Even when therapy is over, this is going to be lifelong.

I tell patients that if the hormone-producing organs are affected by immunotherapy, they’re broken. Once they’re broken, we can’t fix them, but we also can’t break them again. If you develop hypothyroidism and are committed to taking a thyroid replacement medicine, you can continue on therapy because we’ve essentially fixed the problem, but the problem is lifelong. The same thing happens if you develop adrenal insufficiency or have insulin-requiring diabetes. [There is] very, very low incidence, but if it happens, you have to manage that issue with medications for the rest of the patient’s life.

Sunandana Chandra, MD, MS: Dr Pavlick, are you worried about the age of the patient and their tolerability of these immunotherapies?

Anna C. Pavlick, DO: Usually not. These are exceedingly well-tolerated medications. I can confidently sit in this chair and tell you I have a 98-year-old patient getting immunotherapy right now for locally advanced cutaneous squamous cell carcinoma because his performance status is exceedingly good. He has essentially no concurrent medical issues and is an exceedingly well 98-year-old. You can’t discriminate treating patients based on a chronologic age. Many times you can have younger patients in their 50s and 60s with many chronic medical issues who are at a much higher risk of getting toxicity than this 98-year-old.

Transcript edited for clarity.