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Considerations for Hedgehog vs Immunotherapy in Patients with Basal Cell Carcinoma


Experts in dermatology comment on the patient considerations required when deciding on systemic treatment for basal cell carcinoma.

Sarah Arron, MD, PhD: The hedgehog pathway inhibitors, the oral medications have been approved for a longer period of time. I know the approvals for immunotherapy are a little bit newer. Although, we have experience with those medications for other skin cancers, so not new in our hands. We talk about immunotherapy for patients when hedgehog pathway inhibition is not appropriate. Are there cases where you go directly to immunotherapy?

Nathalie Zeitouni, MD, FAAD: Yes. I think currently the way it is indicated is if the hedgehog pathway inhibitor is, if a patient is either intolerant or has progressed on it or who’s not appropriate. The question is who are these patients who may not be appropriate? Well, they may be patients who decline it, so they would be considered inappropriate. Either they’ve heard about the experience, they read about the adverse reactions, or for whatever reasons they decline it. I’ve also had 1 particular patient who had a lot of muscle cramps due to his MS [multiple sclerosis] and talking to his neurologist and the decision was he would not be appropriate for a hedgehog pathway inhibitor. We could shift and consider at that point immunotherapy or a checkpoint inhibitor. So there are just patients who are inappropriate. How about yourself?

Sarah Arron, MD, PhD: I have found that the majority of my patients on hedgehog pathway inhibitors will have some side effect, either the muscle cramps that you mentioned, change in taste, or hair loss. For many patients, these are tolerable side effects, but they can be very wearing over a long course of treatment. My experience with immunotherapy is the majority of patients tolerate it very well, and only a very small number of patients have very significant side effects. Sometimes I’m discussing with the patient what their overall health status is, and we opt for immunotherapy because of other issues in their health. One thing I’m really keen to see in the future as we move towards immunotherapy as a presurgical or neoadjuvant in earlier stage melanoma, and we’re starting to see some research in squamous cell carcinoma. I think it would be a very interesting topic to address in immunotherapy. I know we and others had a small neoadjuvant presurgical trial with vismodegib , one of the hedgehog pathway inhibitors. I haven’t seen that yet for cemiplimab for the PD-1 inhibition, the immunotherapy for basal cell, but I’m hoping that’s something that could come next. Have you tried any neoadjuvant treatments?

Nathalie Zeitouni, MD, FAAD: We have some experience with neoadjuvant more in for patients with squamous cell carcinoma and 1 patient with Merkel cell carcinoma. When they do respond, they respond very, very nicely. So it’s very encouraging also for basal cell carcinoma, the potential, or neoadjuvant for patients with advanced basal cell carcinoma. I guess, one of the questions is when we look at the data on checkpoint inhibitors for basal cell carcinoma, and we see the overall response rate. In a lot of these cases, patients have been heavily pretreated. They’ve had other treatment options, and then they respond. Some of the patients, they take a while to respond and then they respond. Then some patients may seem to have more stable disease. What’s the importance of stable disease for some of these patients in your opinion? How important is that?

Sarah Arron, MD, PhD: I think stable disease is incredibly important, particularly when we can keep a tumor from progressing that does threaten, you know, a vital function like vision, the eye, or a tumor that’s quite close to the mouth where ulceration might interfere with eating. If we can keep that from growing, give the patient both the benefit of better quality of life during that time and also a longer life expectancy. Stable disease as part of cancer management is sometimes underrated, particularly in really advanced tumors where we don’t have other options. One of the things I learned from the medical oncologists that I trained with is that stable disease can often give a patient time for the next blockbuster treatment to be invented and tested. So when we think about some of the patients with early melanoma treatments where we had nothing and now we have a lot, I’m hoping for basal cell cancer we’re going to this type of option developing rapidly as it has been.

Nathalie Zeitouni, MD, FAAD: That’s wonderful. I totally agree and I share that viewpoint. I think it gives hope to continue on with their lives until either something else happens or until, you know. I agree. We don’t talk a lot about stable disease, but I think it is, if we can offer that, that’s wonderful.

Sarah Arron, MD, PhD: Four patients of mine who’ve had anxiety with entering the health care system and trusting doctors. I’ve also found that hands-on management and the time to develop that relationship is really important in building that trust for treatment.

Nathalie Zeitouni, MD, FAAD: It takes time. It takes time to develop that relationship and that trust. I think one of the things we also don’t discuss is, even when we work in a multidisciplinary fashion and we do refer to the medical oncologist, our part doesn’t end really. We’re still the quarterback there. We’re still with the patient, and I do circle back with the patient even after tumor board, “Hey, did you see Dr so-and-so or doctor…so what do you think?” And it’ll be, “Yes. You know, I love that doctor you referred me to. I’m going to do that treatment. But he said also to follow up with you when I’m done,” and so we’ll make that appointment. We keep circling back because that’s the initial relationship and that’s where the trust is, and I think that that’s really key to maintaining those kind of long-term relationships because oftentimes those patients will need our long-term care.

Transcript Edited for Clarity

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