Approximately a decade ago, we had a study that was run out of Australia looking at whether adding chemotherapy to surgery and radiation would affect [a] patient’s risk of recurrence, death, or event-free survival. [There was] no benefit of adding chemotherapy shown in that trial. That was the POST trial run through by the Tasmanian [Radiation] Oncology Group.
[At that stage, we began considering whether we could swap out chemotherapy for immunotherapy—taking a page out of melanoma treatment, where adjuvant immunotherapy has demonstrated a recurrence-free survival benefit and became the approved approach for high-risk melanoma.] We wanted to consider that as well in patients with high-risk squamous cell carcinoma.
An interesting topic is whether it is beneficial to give patients immunotherapy in the adjuvant setting or wait for them to recur and then give them immunotherapy in the metastatic or salvage setting when they are no longer resectable. [This is a challenging question that requires balancing toxicity with potential benefit.] The best way to answer that and to provide a rationale for how you might consider this for your patients is through a robust, structured clinical trial—which is what C-POST was. That’s why it took such a long time to complete the trial and get the data.
[We really focused on the very high-risk subgroup—those patients with extensive regional metastases, lymph node disease with high-risk features, or those with very high-risk primary tumors demonstrating perineural invasion, bone invasion, or other aggressive characteristics.] These are the patients we worry about the most. So, the rationale was: can we prevent recurrence or poor quality-of-life outcomes by potentially offering therapy earlier, upfront?
[This has been a long process—eight years—and during that time, the field evolved, particularly with the use of immunotherapy before surgery (neoadjuvant therapy), which has shown robust success.] The question then became: should we consider neoadjuvant or adjuvant therapy? [It’s complex, as every patient and clinical scenario differs.]
[What I will say is that I’m pleased to he this—not because it’s the definitive approach—but because it gives our patients options.] Sometimes we perform surgery expecting a good outcome, but later find higher-risk features than anticipated, or a patient undergoes surgery and radiation, and we remain concerned about recurrence. [Now, we he strong data to guide that decision if the clinical situation fits.]
What was the design of the C-POST trial?An important point for the study design is that this is adjuvant therapy given after surgery and radiation, so all patients needed to undergo surgery and then complete radiation within a relatively short window. [This ensured the timely completion of postoperative therapy.] Despite this standard approach, as I mentioned earlier, 30–40% of patients with the highest-risk features still recur.
[The trial was a randomized, placebo-controlled design comparing cemiplimab with placebo, allowing for a true “apples-to-apples” comparison.] This strict design strengthens the conclusions we can draw from the data and makes the results even more meaningful. [Specifically, cemiplimab reduced the risk of recurrence or death by 68% compared with placebo (HR, 0.32), which is among the most impressive results in the adjuvant immunotherapy setting—exceeding what has been seen in melanoma.]
What additional insights do the DFS findings from C-POST provide about cemiplimab’s clinical benefit?[The disease-free survival data were indeed impressive—not only for regional disease recurrence but also for distant metastases.] The benefit was extended to both, with hazard ratios around 0.2 for regional and 0.35 for distant recurrence. [That’s notable because CSCC is primarily a regional disease, but a subset of patients develop distant metastases.]
Now, the question becomes whether there will be an overall survival benefit. [That needs to be examined carefully, since CSCC differs from melanoma—patients are generally older, and recurrences can occur later in life, making treatment more challenging.] So, should we focus on overall survival, quality of life, or simply recurrence prevention to oid aggressive interventions later in life? [Those are the key questions for long-term follow-up.]
What key points should be noted about the safety profile observed in the C-POST trial?Yeah, so we can say the safety profile showed no new signals and was consistent with expectations for immunotherapy, specifically cemiplimab. [Treatment was well tolerated, with only 10% of patients discontinuing and 22% experiencing temporary interruptions, most of whom were able to resume therapy.]
[Unlike metastatic treatment, the adjuvant regimen has a defined duration, which likely contributed to tolerability. This also helps address whether adjuvant or later-line therapy is preferable—again, that depends on the individual patient and scenario.]
What key points should be noted about the safety profile observed in the C-POST trial?[There are two main takeaways.] First, when clinicians see this and think about “high risk,” I urge them to understand the trial design and inclusion criteria. [The benefit was seen in patients with very specific nodal and extranodal risk features—so it shouldn’t be applied too broadly.]
Second, when comparing this to neoadjuvant approaches, it’s not a question of which is better—it’s about giving patients options. Some may he already undergone surgery before discussing immunotherapy. [Now, with an approved indication, we can confidently offer adjuvant cemiplimab in those scenarios to help prevent recurrence.]
ReferencesFDA approves cemiplimab-rwlc for adjuvant treatment of cutaneous squamous cell carcinoma. FDA. October 8, 2025. Accessed October 8, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-cemiplimab-rwlc-adjuvant-treatment-cutaneous-squamous-cell-carcinomaLibtayo (cemiplimab-rwlc) approved in the U.S. as first and only immunotherapy for adjuvant treatment of cutaneous squamous cell carcinoma (CSCC) with a high risk of recurrence after surgery and radiation. News release. Regeneron. October 8, 2025. Accessed October 8, 2025. https://investor.regeneron.com/news-releases/news-release-details/libtayor-cemiplimab-rwlc-approved-us-first-and-only