Case 1: Data Supporting Anti-PD-1 in cSCC

EXPERT PERSPECTIVE VIRTUAL TUMOR BOARD

Ahmad Tarhini, MD, PhD:How was this patient managed?

Kevin S. Emerick, MD:This patient ultimately needed an auriculectomy as his primary surgical option. The patient, perhaps understandably, did not want to have that surgical treatment, and therefore, underwent treatment with cemiplimab in an every-2-week fashion.

Ahmad Tarhini, MD, PhD:It would be great if you could review the phase II data with cemiplimab in locally advanced disease.

Kevin S. Emerick, MD:Yes. We have some recent data within the last couple of years looking at cemiplimab in a locally advanced population. Locally advanced, in this particular study, was focused on those tumors that could not be removed with surgery. Those patients were then given cemiplimab every 2 weeks for 96 weeks. In general, as you’d expect in this kind of a trial, these were generally healthy patients, in terms of that inclusion criteria.

There were a couple of key exclusion criteria. One is an obvious one, in terms of thinking about immunosuppressed populations—solid organ transplants. This type of therapy may lead to rejection in those patients, as they have to come off of their immunosuppression.

The second group that was excluded were patients with hematologic malignancies, especially those patients with CLL [chronic lymphocytic leukemia]. That’s an important thing to note, because this is an important population for high-risk cutaneous squamous cell. So that population was excluded from this trial.

If we look at that study, one of the key things is recognizing that about 70% of these patients’ tumors are from the head and neck region, which fits with the demographic we’d expect for these types of tumors—the vast majority occurring in the head and neck region because of sun exposure.

Many of these patients had actually had some form of treatment before, including previous radiation or a systemic treatment. The study was broken down into both those patients with locally advanced as well as regionally and distant metastatic disease. But focusing specifically on the locally advanced population, there were 26 patients, overall, in this part of the phase I study with locally advanced disease, and about 50% of them had a good response.

As we think about response for these patients, we want to think about who’s having complete responses [CRs], partial responses, and stable disease. Each one of those is important for this locally advanced population. These tumors can cause significant symptoms. And so, even for responses that are short of a complete response, this is important. Thirteen percent of these patients had a complete response, about a third of them had a partial response, and another third had stable disease. So disease control in this trial was excellent, with almost 80% of these patients having either stable disease or at least some type of response. Of those who had a response, many of them had an excellent durable response—a 63% durable response, meaning that at 6 months that response had held up.

Ahmad Tarhini, MD, PhD:In terms of your practice in the clinic, Dr McKean, what type of responses to cemiplimab do you expect in a patient like this?

Meredith McKean, MD:I’d say with patients like this, clinically you can sometimes see very nice dramatic responses, even within the first several months. I think one thing that we’ve learned from the clinical trial and from patients treated clinically is that sometimes you can see patients who will have a slight increase in the tumor. It can become a challenging situation to decide if that’s true progression versus inflammation of the tumor, but I think what we’ve seen is to continue treating those patients and see if that response presents itself and the patient does end up having shrinkage.

Ahmad Tarhini, MD, PhD:And in your practice, does this happen within the first few weeks? How soon do you think it usually happens, to think it potentially is progression?

Meredith McKean, MD:What I’ve seen is that the tumors will increase very early on. And so, it’s not necessarily something that I’ve seen very late, 8 months in, where they are increasing in size, and would then still be kind of tumor infiltration.

Ahmad Tarhini, MD, PhD:And the general thought is that it’s potentially inflammation, or it’s immune infiltration, increased T-cell infiltration, and other factors leading to this kind of transient growth in size followed by shrinkage. Have you used cemiplimab in your practice?

Meredith McKean, MD:I have. I have found that it’s been very well tolerated by patients. The adverse effect profile is very similar to other anti—PD-1s [anti–programmed cell death protein 1 antibodies], so I’m able to use those same expectations of adverse effects seen from the clinical trial and with other anti–PD-1s.

Ahmad Tarhini, MD, PhD:And how long do you continue treatment with cemiplimab in a patient like this?

Meredith McKean, MD:It’s challenging, because looking long term for patients who are able to have a nice dramatic response, a lot of it comes down to conversations with those patients where you say, “How well are you tolerating this?” And, “How comfortable are you with continuing treatment if you’ve been able to achieve this CR?” Versus continuing therapy for up to a year, or maybe even 2 years for patients who may still have some residual disease. You also consider, if there is some disease or what appears to be disease, rebiopsying to see if there is still an active tumor.

Ahmad Tarhini, MD, PhD:It appears, obviously, especially in the locally advanced cases where surgery and maybe radiation therapy could still be an option to achieve a CR, that we understand that a group of patients will achieve CR, but not everybody. So taking the patient back to the multidisciplinary tumor board, involving the multidisciplinary discussion, appears to be very important. And in my experience, I’ve had patients who went back, for which we did surgery after an initial response if we did not achieve a CR, for example.

Transcript edited for clarity.