Key opinion leaders discuss the positive impact of cemiplimab in their personal practices along with the off-label use of pembrolizumab and cetuximab in CSCC management.
Omid Hamid, MD: My personal experience with cemiplimab has been great. We were fortunate enough to be part of the phase 1 trials of this agent, looking at basal cell carcinoma. What I can say is that when the patients actually benefit, they have a significant benefit. The appropriate patient is a patient who is not a candidate for further surgery or radiation. This may be due to a case of multiple recurrences or because surgery or radiation is not indicated due to the extent of disease, whether it’s locally advanced or metastatic.
The contraindications to this therapy are patients who have any type of autoimmune disease, who’ve had any type of transplant, or who’ve had any type of previous toxicity with immunotherapy. We look at these patients as a 1-to-1, evaluate the risks and benefits, and have a discussion about cemiplimab in their disease state.
Morgana Freeman, MD: I like to use cemiplimab in my practice. Unfortunately, it’s the only FDA-approved therapy, but what’s good is we actually have an FDA-approved therapy now. Unless there is some reason that the patient wouldn’t or shouldn’t get the drug, in the event of coexisting autoimmune disease, for example, or some concern that the patient could develop a significant immune-related adverse event, it’s a green light as far as I’m concerned. Patients like it. It’s a 30-minute infusion, every 3 weeks. In the case of locally advanced CSCC [cutaneous squamous cell carcinoma], when I explain to them that they may see results within the first 2 to 3 infusions, that’s very encouraging for them.
In my practice, I oftentimes will have that discussion very early. I’m fortunate the surgeons that I work with recognize that I’m a proponent of this therapy, and they’ve seen the outcomes that I’ve been able to achieve. The point that I would make to medical oncologists listening to this interview would be to encourage surgeons to refer early. Don’t wait until that patient has developed distant metastases. Get us involved early in the conversation, so that we can talk to patients about the benefits of systemic treatment.
Omid Hamid, MD: Pembrolizumab is similar to cemiplimab. It’s a PD-1 [programmed cell death protein 1] inhibitor. It has done its own trials in this subgroup of patients and has seen data that are remarkably similar. Therefore, they’re moving on to get an approval in this indication.
Cetuximab is an EGFR inhibitor that’s being used in head and neck cancer—squamous cell head and neck cancers. It is a standard therapy for those patients. Given similar mutations seen in cutaneous squamous cell carcinoma, it is being looked at off-label for patients with cutaneous squamous cell carcinoma of the skin. We have seen very minimal benefit as a single agent. But because the combination of this agent with anti—PD-1 immunotherapy has been shown to be tolerable, there are ongoing trials looking at this regimen, only in clinical trials, for patients with cutaneous squamous cell carcinoma of the skin.
For me, I use cemiplimab because it’s FDA approved. But if there was a clinical protocol with pembrolizumab, I would utilize that protocol for patients—like a clinical trial of a combination, or other. Cetuximab has a role in combination with immunotherapy through clinical trial. Those trials are ongoing looking at patients who are untreated or refractory to initial immunotherapy. That’s the major issue for us—these patients who don’t respond. How can we increase response for them? Combination therapy may be the answer.
Classically, high tumor mutational burden indicates a response rate to immunotherapy. The tumors with the higher mutational burdens, such as in lung cancer and melanoma, are the ones that have seen the best responses to immunotherapy.
Interestingly, when we presented those graphs and tables of high tumor mutational burden, we left off the tumor with the highest tumor mutational burden. That’s cutaneous squamous cell carcinoma. Therefore, we would expect to see high response rates, which is what we saw in our clinical trial.
In fact, there is a subset of cutaneous squamous cell carcinoma that has a higher tumor mutational burden, and those are patients with immunosuppressed or post-transplant cutaneous squamous cell carcinoma. We’re still trying to find the right control between giving immunotherapy and getting benefit, and giving immunotherapy and having toxicity.