Sherrif F. Ibrahim, MD, PhD, and Vishal Patel, MD, FAAD, FACMS, provide initial impressions of the case and discuss the use of immune checkpoint inhibitors.
Sherrif F. Ibrahim, MD, PhD: Right away, I felt that she had a couple options here. We could potentially do surgery, which would be very invasive. Imaging showed that this was very deep into the subscapularis muscle. It would have been very extensive, debilitating surgery. We talked to her about systemic treatment with hedgehog inhibitors. But to get your high-level overview, how would you characterize this patient’s risk for potential metastatic disease or adverse outcome from surgery or other systemic treatments? What are your initial thoughts when you see something of this magnitude?
Vishal Patel, MD, FAAD, FACMS: As we mentioned earlier, this is clearly a locally advanced basal cell carcinoma. If you utilize staging risks, this has at least 2 of the high-risk features of being greater than 4 cm and invading deeply beyond the fat. We’re getting into the group of tumors with a high risk of poor outcomes, recurrence, and metastases. If you aren’t used to the European guidelines for staging, assessment scores go from 1 through 5, easy vs hard to treat. Five is giant, [a] deeply invasive clinical disaster. Clearly, when this case walks in the door, you’re first thinking that this is a 5-type case and a multidisciplinary case, where you need to discuss to figure out the [best] option and what the patient wants.
Sherrif F. Ibrahim, MD, PhD: When surgical oncology met with her and saw the imaging, they said, “Let’s start hedgehog therapy and see how she does.” Her biggest concern was hair loss. She did very well on the hedgehog therapy. She kept her hair. She didn’t get any alopecia. She tolerated it well, with only nuisance adverse effects.
Suppose this patient didn’t respond. Let’s say you’re on maybe a month, 2 months, or 3 months of oral hedgehog inhibitor therapy, or they had progression of disease. What would you consider next as far as systemic treatments?
Vishal Patel, MD, FAAD, FACMS: Starting a patient on hedgehog inhibitor therapy would likely be my first choice as well in this case. It’s first-line treatment for locally advanced [basal cell carcinoma] when surgery is going to be quite extensive. I’d also be worried about potentially some metastatic focus that hasn’t been picked up and being able to get that under control. In this patient, I’d expect to see response, and I believe we have some pictures of how her response occurred. But if that response stopped and she developed other lesions, then the discussion is around whether surgery at this point makes sense or whether we move to immunotherapy.
Cemiplimab therapy makes a lot of sense, depending on how much of a response you’ve seen and if you have small foci to act, add another mechanism to get clearance here. That would definitely enter into our discussion, but then the discussion would become length of treatment and what the risks and adverse effects are. I tell patients with new checkpoint inhibitor therapy that most patients tolerate it really well, but about 10% of patients will have some life-altering adverse effect. They may have to take medication or temporarily be hospitalized and then their dosing is modified. One percent have died from treatment with immune checkpoint inhibitor. That’s a much lower risk than patients who don’t have optimal treatment of their metastatic tumor, but it’s important to think about. Or maybe surgery makes sense in this patient. I’m curious to know exactly what happened with her response and what path you went down.
Sherrif F. Ibrahim, MD, PhD: First, she had a very rapid initial response to oral hedgehog therapy that lasted on the order of about 3 months. She tolerated it well, but then we noted some progression in the form of regrowth of her tumor. At that point, the areas of regrowth were small enough that they were amenable to Mohs surgery in the office, which we did, and she’s done well now.…
Vishal Patel, MD, FAAD, FACMS: Just of those areas that were growing.
Sherrif F. Ibrahim, MD, PhD: Just of small foci of tumor. But certainly, if we had done scouting biopsies and saw substantial residual basal cell, in our practice this would be an ideal candidate to start considering systemic immune checkpoint inhibitor treatment with cemiplimab, because this is exactly the type of patient that was enrolled in the trial, that did well in the trial, that failed hedgehog therapy. And now we have this other option, which is fantastic and exciting.
Vishal Patel, MD, FAAD, FACMS: The other thought process that is important to bring up is that we’ve talked about overall response rate, but with skin cancers, sometimes it’s the durable response and control of tumor growth that can be a more important measure. Because if patients are under control and have quality-of-life improvement, then that may check off the boxes that they need to be functional and to manage with this.
It’s interesting to have surgery around those foci to know whether the hedgehog inhibitor treatment is pushing the tumor to a more squamous potential, and whether that will respond to immune checkpoint inhibitor even higher than those clinical trials for basal cell. These are areas that we’re trying to figure out as more data in these patients are followed out. Or how can we predict whether they will respond to help us move toward surgery or toward immune checkpoint inhibitor at that progression standpoint?
I should also make a plug that at that 3-month mark, the magic number when the adverse effects for hedgehog inhibitor therapy start to rear their ugly heads, there are alternate dosing regimens that have been evaluated in a randomized clinical trial fashion. The…trial that was done mainly in Europe looked at alternate dosing and showed [that] the group that was on treatment for 12 weeks and then had 8 weeks of placebo off treatment essentially had fewer adverse effects and improved response rates compared with patients who were treated for a longer period and then stopped. There are other potential options, but I agree with you. I’d certainly consider moving to immunotherapy with cemiplimab for a patient who progressed after 3 months of hedgehog inhibitor therapy.
Sherrif F. Ibrahim, MD, PhD: It’s true to say that we’ve barely scratched the surface on understanding where the immune checkpoint inhibitors fit into our management plan. We’re all very excited to have the option, and it’ll be interesting to see how the data unfold over time as more of us refer these patients for this class of treatment.
With that, I’d like to wrap up. I want to thank you again, Dr Patel, for joining us. Thank you for watching this Dermatology Times® Recognize & Refer presentation. I hope you found it rich and informative and took away some learning points. Thanks again.
Transcript edited for clarity