Derm Advances: Insights From Dr Vishal Patel on the C-POST Press Release

Watch Dr Vishal Patel discuss the early data from the C-POST phase 3 clinical trial of Libtayo (cemiplimab) as an adjuvant treatment for high-risk cutaneous squamous cell carcinoma (CSCC) after surgery and what this data could mean for the future of high-risk CSCC treatment and outcomes.

Dr Vishal Patel: Hello, my name is Vishal Patel. I am a Mohs surgeon and dermatologic oncologist based in Washington, DC at the George Washington University School of Medicine, where I serve as the director of Cutaneous Oncology at the GW Cancer Center. And today, we're going to be discussing the very exciting press release news about early outcomes, early data, top-line data, that has just been released in the C-POST trial evaluating, in a randomized fashion, adjuvant cemiplimab compared to placebo in high-risk resectable locally advanced squamous cell carcinoma treated with surgery and radiation. 

Question 1: What are your general impressions of the latest C-POST trial data? 

Dr Vishal Patel: Well, we have just received some highlight bullet points from the C-POST data, which will be released and presented at the upcoming ASCO meeting in late May, early June of this year. This information was released by press release, by the company, highlighting some very impressive outcomes. And this was really an eye-opening and exciting result to see—being able to reduce patients' risk of recurrence and improve outcomes in those patients that were treated with adjuvant cemiplimab. 

Question 2: Did any of the findings stand out to you as particularly noteworthy or unexpected?

Dr Vishal Patel: Well, what's especially noteworthy and required some more evaluation is the fact we actually had 2 trials being run in this space. One being, evaluating cemiplimab, which is the C-POST trial. And the other, looking at adjuvant pembrolizumab, which is one of the KEYNOTE trials, KEYNOTE-630. And compared to this press release, which shows that impressive benefit in patients treated with adjuvant cemiplimab, the KEYNOTE-630 study was actually halted just a few months prior. And we received that information also by press release, noting that there was not a benefit or that the trial had failed based on the way it was designed. 

Now, we're not really sure about the exact details of the reason for that failure and discontinuation and how we're going to compare that to the adjuvant cemiplimab C-POST trial. This is what we're hoping to glean in the next few months so that we can be able to apply this to our patients—who are the highest of the highest risk who have surgically resected disease—and know how to best treat them. But for now, we're really eager to see that C-POST data because this certainly is the subset of patients that we worry about the most. And as opposed to the way the field has moved towards nonresectable or even potentially neoadjuvant therapy in those patients where we have performed surgery and we worry, we need to do something more. But we now potentially have an option, and we'll get more information about that in just a few months. 

Question 3: Libtayo reduced the risk of recurrence or death by 68% compared to placebo. How do you interpret the magnitude of this benefit in the context of managing post-surgical CSCC patients? 

Dr Vishal Patel: Well, that reported 68% benefit is quite remarkable. Just to give us context, a hazard ratio reduction about 0.32—is about as good as it gets in the adjuvant world. And compare that to other types of tumors, melanoma, it certainly blows it out of the water when we think about these high-risk, resectable patients. And so, that magnitude is quite high, but also it helps provide us a therapeutic option in some of the patients that are the hardest to manage. In locally advanced cutaneous squamous cell carcinoma, especially those that have the clinical pathological high-risk features that were enrolled in this trial— multiple lymph nodes, large caliber nerve invasion, intransient metastases, amongst other criteria—oftentimes, we don't realize the extent, or we've upstaged the patients to realize they have multiple high-risk features. And these patients have 30%, 40%, 50% risk of the tumors coming back down the road. We've utilized radiation therapy in those patients to reduce that risk. But the data on that is variable in terms of how good of an impact or how good we can predict how those patients will do. And so, seeing this type of result is really going to change how we counsel these patients and consider incorporating this therapy after those patients have had surgery. And we have identified that they are truly high risk or the highest of the high risk for poor outcomes. 

Question 4: How does this efficacy data compare to what you currently observe in patients managed with surgery and observation alone? 

Dr Vishal Patel: So, as I noted before, the gold standard of treatment for high-risk, resectable tumors—some of the very high risk per NCCN criteria or locally advanced tumors with nodal disease—has been surgery and radiation. And that efficacy of that approach is variable. Some patients do see a durable response. But it's unclear if that therapy truly provides an additive benefit of adjuvant radiation across the wide spectrum of patients that present. That being said, that is the standard care of therapy, but we have a margin to improve upon for these patients. And so, with this data and this press release, we really are excited because it really takes those patients to the next level in terms of preventing their disease. 

This is especially important for dermatologists because oftentimes while we're not managing patients with lymph node metastases, we do manage advanced tumors or may not realize a tumor is as advanced as it is until we begin to resect, perform Mohs surgery, and then upstage them with multiple high-risk histologic features. And in those patients that are similar to those that were enrolled in this trial will now be—potentially—could be eligible to receive this treatment if there is approval of this therapy based on this data. And so, I'm extremely optimistic and excited to now be able to offer patients another therapy, if this does receive approval, that will go beyond the standard of care of surgery and radiation, which really doesn't get to where we want to for these high-risk patients. 

Question 5: Could these findings influence how early dermatologists engage with immunotherapy decisions, particularly in multidisciplinary care settings? 

Dr Vishal Patel: Absolutely, I think dermatologists have always been a gatekeeper for cutaneous malignancies. We have the longest touch point with our patients for years before sometimes they develop some of the most advanced tumors, or they oftentimes are the referring providers where advanced skin cancers initially present to. And so, it's especially critical for those providers to be familiar with these therapies to involve those multidisciplinary experts—or as I noted, you may not realize that a tumor is quite as advanced until a surgical resection is done, and the tumors upstage to have those types of very high-risk features that lead to poor outcomes.

And so, for dermatologists to be thinking about immunotherapy either earlier, with some of the data we saw in the last 2 years with neoadjuvant therapy, neoadjuvant cemiplimab, having robust and durable outcomes in patients given before surgery. Well, now we also will potentially have data that shows that if patients did not receive or were not candidates or just were not considered for immunotherapy early on, and then we have high-risk features, there may be an opportunity or an option to provide immunotherapy on the back end in an adjuvant setting and improve on the outcomes of the standard therapy of surgery and radiation. So, especially critical for dermatologists to think about this and then incorporate the multidisciplinary team with their patients. 

Question 6: What questions do you still have about patient selection, long-term outcomes, or biomarkers in this setting?

Dr Vishal Patel: Well, we still have a way to go to really understand how to best predict which patients will respond to what type of approach—whether using the therapy early or neoadjuvant or after surgery, being able to identify those who are at risk of adverse event profile if they truly will see a benefit in the adjuvant setting, or do we just wait for the tumor to come back? But just as a whole, I think we are getting lots of answers when we think about the high-risk features. This trial certainly had patients—it had very specific characteristics that were enrolled. So, in many ways, we'll be able to at least predict with a high level of certainty which patients are those that may benefit. But those questions about biomarkers and response are going to become increasingly more important as we move that treatment earlier in the neoadjuvant fashion. 

And what's probably going to be most relevant to dermatologists is that it's also now cemiplimab being evaluated in the intralesional fashion for earlier-stage, lower-risk tumors and being able to predict maybe which tumors that might be best for. That's still a ways away. And then, what the next few years of our work may entail in showing an efficacy when injecting cemiplimab straight into tumors and also being able to predict which ones are going to respond versus which are not to be able to help us identify where we can consider using that treatment. 

Question 7: What additional data would help you feel confident about integrating adjuvant immunotherapy into dermatologic care pathways? 

Dr Vishal Patel: Just like with any type of systemic therapy, certainly in the oncology realm—you know, as dermatologists, we think about things where we can see with our eyes, looking at skins and patients clearing up and having sustained responses. Oncology can be slightly different in that it's harder to measure the response to systemic therapy, certainly when there are metastatic or internal foci of tumors, of metastases. And so, having longer-term data in seeing that patients do well, continue to do well, have durable responses, and are surviving longer or have an improved quality of life are the key metrics in oncology. So, we still need that data to come out to show us that what we do believe that this early data should reflect upon our patients will be the case. So, we will continue to look out for that and report that out. But, as we have seen with melanoma, with some of the earlier cemiplimab data, this is clearly a class-specific effect across the classes of immunotherapies and across both melanoma and non-melanoma skin cancers. So, our expectation is that our patients will continue to do well, and we can confidently implement this in and really represents a paradigm shift for non-melanoma skin cancer.