Dr. Scott M. Dinehart discusses the important roles of hedgehog inhibitors for treating skin cancers, as well as potential uses for cemiplimab and imatinib.
Scott M. Dinehart, MD, Dermatologist and MOHs surgeon with Arkansas Dermatology, Little Rock, Arkansas
“If you know me, what’s always hot are hedgehog inhibitors. I think that they are underutilized in dermatology. I want to put aside the myth that they don’t work. They work very well,” said Scott M. Dinehart, MD, dermatologist and MOHs surgeon with Arkansas Dermatology, Little Rock, Arkansas, who presented “What’s New and Hot in Derm Oncology,” at Winter Clinical Dermatology Conference 2022.
“Experts, including myself, think that 90% of patients can benefit from hedgehog pathway inhibitors,” he said.
Hedgehog inhibitors target the signaling pathway involved in basal cell carcinoma (BCC). The available hedgehog inhibitors vismodegib (Erivedge, Genentech) and sonidegib (ODOMZO, Sun Pharma) are efficacious, but adverse events can pose challenges, said Dr. Dinehart.
“Those adverse events are muscle cramps, taste alterations (dysgeusia), and hair loss.”
A published review suggests more than a quarter of patients stopped treatment because of side effects from hedgehog inhibitors.1 To get those under control, Dr. Dinehart shared two tips:
“The first is to decrease the frequency of dosing with hedgehog inhibitors. Go from daily dosing to 10 to 15 days per month. It will slow down the efficacy a bit but will dramatically reduce the adverse events.”
The second tip is to use L-Carnitine to minimize muscle cramps, he said.
“L-Carnitine is an over-the-counter amino acid that you can get on Amazon or GNC, and it dramatically reduces the muscle cramps. Start it a couple of weeks before the hedgehog inhibitor, and you’ll reduce the muscle cramps to where the patient can tolerate the medicine.”
Vismodegib Vs. Sonidegib
According to Dr. Dinehart, vismodegib and sonidegib are similar hedgehog inhibitors and choosing which to use is up to the dermatologist.
“Vismodegib came out first. They have a lot of similarities. I think they work equally well. The numbers may be a little bit better for vismodegib than sonidegib but not statistically. The problem with sonidegib is that it does have some drug-drug interactions, particularly with CPY3 inhibitors like itraconazole, [also a hedgehog inhibitor].”
The sonidegib package insert also indicates the need to draw bloodwork because of concerns about elevated levels of creatinine and creatine kinase (CK), said Dr. Dinehart.
“[The insert] mentions rhabdomyolysis several times. Rhabdomyolysis is not in the vismodegib package insert.”
Nevertheless, either hedgehog inhibitor can be used, said Dr. Dinehart.
“So, I think vismodegib does have the market share, but certainly if you felt comfortable with sonidegib you could use it. I’m not so much a vismodegib versus sonidegib person, I’m more like, ‘I think [hedgehog inhibitors are] just underutilized’ period.”
The message, according to Dr. Dinehart: “Start using hedgehog inhibitors. Pick which one you want. You will help your patients.”
Cemiplimab is Hot
Cemiplimab-rwlc (LIBTAYO, Regeneron/Sanofi) is a monoclonal antibody approved to treat basal cell and cutaneous squamous cell carcinoma, said Dr. Dinehart.
“Cemiplimab is hot. We’ve been using it for a couple of years for squamous cell carcinoma. It’s very effective. It works very quickly. It works for metastatic and advanced disease.”
“Advanced cutaneous squamous cell skin cancer kills more people than melanoma. I’ll say that twice. Advanced squamous cell skin cancer kills more people in this country than melanoma. It’s a terrible problem. Cemiplimab, right now, is our answer.”
Not only does cemiplimab work quickly, but Dr. Dinehart loves the way it shrinks tumors.
“I love [cemiplimab] when you have a positive margin afterwards. It works great pre- and postoperatively. It also has this new indication for basal cell [carcinoma]. I don’t have as much experience because I’m kind of a hedgehog guy… but I do have a couple of patients on it and they’re doing very well.”
Dermatologists prescribing it for basal cell carcinoma need to be patient, he said.
“Cemiplimab does not work as quickly for basal cell as it does for squamous cell.”
Imatinib for DFSPs
“I’ve also been asked about imatinib (GLEEVEC, Novartis) for dermatofibrosarcoma protuberans (DFSPs),” said Dr. Dinehart.
“I’ve treated over 120 DFSPs in my career and I haven’t had to use this therapy, but I wouldn’t hesitate to [use imatinib], particularly if I had something in a very critical area or pre- and postop. …most people tolerate this medicine very well. I have a couple of patients who are on it for leukemia, and they’ve been on it for 5 or 10 years.”
Checkpoint Inhibitors for Merkel Cell
“The other thing I’ve been asked about is the use of checkpoint inhibitors for metastatic Merkel cell. I would tell you that this is also working out very well for us. Just like immunotherapy works well for melanoma, [checkpoint inhibitors are] working well for Merkel cell patients,” he said.
“I’ve treated over 120 DFSPs in my career and I haven’t had to use this therapy, but I wouldn’t hesitate to [use imatinib], particularly if I had something in a very critical area or pre- and postop. …most people tolerate this medicine very well. I have a couple of patients who are on it for leukemia, and they’ve been on it for 5 or 10 years.”
“Outside of angiosarcoma, Merkel cell is probably the worst skin cancer that we deal with. …all of the immunotherapy is terrific. For patients that respond, you’re seeing 85% global remissions, which is equivalent to cure when you talk to patients.”
Dr. Dinehart’s concern is that some oncologists want to use drugs other than immunotherapy first, even though the drugs they use are not approved and are not as effective.
“They kind of wear down patients and by the time they get to immunotherapy, patients are not doing so well. This has diminished as we have gotten more immunotherapy approved. But I’m going to tell you, as the dermatologist, sometimes you have to be the person who will be the patient advocate.”
Disclosure: Dr. Dinehart is a speaker and consultant for Genentech, a speaker and consultant for Regeneron/Sanofi and speaker and consultant for Castle Biologics.
Reference
- Xie P, Lefrançois P. Efficacy, safety, and comparison of sonic hedgehog inhibitors in basal cell carcinomas: A systematic review and meta-analysis. J Am Acad Dermatol. 2018;79(6):1089-1100.e17. doi:10.1016/j.jaad.2018.07.004