CSCC Treatment Options: Cemiplimab and Pembrolizumab

Transcript:

Sunandana Chandra, MD, MS: Dr Khushalani, let’s do a deep dive into these 2 FDA-approved therapies Dr [Anna C.] Pavlick [DO] talked about, cemiplimab and pembrolizumab. If you can comment about those 2 monoclonal antibodies, the trials that led to their approval, if there’s any data behind switching from 1 to another, if there’s no response, and then what do you do when patients progress on those therapies?

Nikhil Khushalani, MD: Sure. I thought I was going to beat Dr Pavlick’s 98-year-old, but I have a 94-year-old who’s getting anti-PD-1 therapy, and we’re doing very well or has already completed treatment done very well. I completely agree on that aspect. This is not an era of chemotherapy where we were always a little bit concerned in individuals who are about the age of 70 or 75. The definition of a geriatric population keeps increasing in our lifetime, which is a good thing. So, yes, I concur with everything that she said.

In terms of the 2 drugs, cemiplimab or pembrolizumab, to me is essentially 6 of 1, half a dozen of the other. They’re virtually identical and target the same pathway. If you look at an equivalent population from the 2 trials that led to their respective approvals, the EMPOWER study for cemiplimab and the KEYNOTE trial for pembrolizumab, the response rates on an average in the frontline setting, immunotherapy naive patients, is approximately 50%. That includes both partial and complete responses [CR].

Cemiplimab certainly has a longer duration of follow-up since it was the first to be approved and tested back in 2018. About 20% of patients treated with cemiplimab for locally advanced or distant metastatic disease go on to developing a complete response. In many cases, these responses, at least in our anecdotal experience, has been durable. The duration of response for patients who have experienced a PR [partial response] or CR has not been reached, but at the most recent update that was presented in ESMO [European Society for Medical Oncology annual meeting] in 2022 on the EMPOWER study, we were able to identify the median progression-free survival [PFS] as well as the overall [survival] [OS] in the 2 metastatic arms, which was arms 1 and 3 on that trial. On average, the median PFS is about 18 months and the median OS is reaching close to 5 years. So these patients are doing very well.

The problem is that almost half of these patients either don’t respond or eventually some of them go on to developing acquired secondary resistance. I don’t think we have a clear winner in the second-line setting. To answer your specific question, should we switch from cemiplimab to pembrolizumab or vice versa if one progresses on 1 agent? The answer is a vehement no; we should not be doing that at all. Some people have considered escalating to combination immunotherapy just like we would do in melanoma. There is no proven prospective data to support that.

On an off-label basis, if other treatments have been exhausted, one would certainly consider that. In our practice, our bias is to use an anti-EGFR agent such as cetuximab in the second-line setting in patients who have progressed on frontline anti-PD-1 therapy. We presented data at ASCO [American Society of Clinical Oncology annual meeting] a year ago looking at our responses to cetuximab in the setting, and we were routinely seeing responses of 50% or greater. And if you look at the older cetuximab data in the pre-IO [immuno-oncology] era, it was about 28% to 30%. Now, is there something that’s being modulated? I think we’re trying to understand that.

There was a separate trial that Paolo Bossi [MD] presented last year and then subsequently published, which is an important study and a very innovative trial. Patients were treated with frontline pembrolizumab, and those patients who had a clear evidence of response at first restaging continued on that line of therapy. Patients who had stable disease or had progression as their best response at first restaging had cetuximab added to that regimen. This was called the I-TACKLE study, and they found that the combination did have a response rate in that refractory population of about 38%.

So that is certainly an option if it can be covered. Again, the combination I will stress is not FDA approved [to use] anti-PD-1 plus anti-EGFR, but there are safety data, and there are safety data in mucosal head and neck cancers as well. But in terms of whether that combination is necessarily better than a single-agent anti-EGFR, I think that remains to be seen.

Then, the third class of agents that one would consider for refractory disease is time-tested chemotherapy. We would use platinum-based regimens, taxane-based regimens, and fluorouracil-based regimens, but as we all know, the responses are modest and durations of responses on an average are between 2 and 4 months, so I tend to use that in the more refractory patient who still maintains a good functional status. Certainly, [enrolling a patient in] a clinical trial at any of these junctures is very appropriate.

Transcript edited for clarity.