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Adjuvant cemiplimab significantly cut recurrence risk and improved disease-free survival in high-risk CSCC, establishing a new standard of care.
The integration of immunotherapy has transformed the management of high-risk cutaneous squamous cell carcinoma (CSCC), offering a path toward improved long-term outcomes, according to Vishal A. Patel, MD, FAAD, FACMS. The FDA approval of adjuvant cemiplimab (Libtayo) underscores this paradigm shift, establishing a new standard for patients who historically faced high recurrence rates following surgery and postoperative radiotherapy.1
In an interview with OncLive®, Patel, discussed the evolving role of immunotherapy in CSCC and the rationale for investigating cemiplimab in the adjuvant setting. He outlined the design and clinical implications of the phase 3 C-POST trial (NCT03969004), which enrolled patients with completely resected, high-risk disease following postoperative radiotherapy. The trial demonstrated a 68% reduction in the risk of recurrence or death with adjuvant cemiplimab vs placebo, reinforcing its role as an effective, tolerable option for patients with high-risk CSCC.
Patel highlighted how these findings align with the broader evolution of immunotherapy use in solid tumors, emphasized the safety profile and practical implications of adjuvant therapy, and underscored how this approval provides oncologists with new opportunities to individualize treatment and improve long-term patient outcomes.
“What’s most important is that this approval provides clinicians and patients with options, especially in cases where recurrence risk is unexpectedly high after surgery and radiation. We now have strong data to guide decision-making when that clinical situation arises,” Patel noted in the interview.
Patel is an associate professor of dermatology at the GW School of Medicine & Health Sciences, as well as the director of the Cutaneous Oncology Program at the GW Cancer Center in Washington, DC.
Patel: We’ve seen a rapid shift in the treatment approach for advanced, high-risk CSCC. Historically, we haven’t had strong, durable treatment options. Standard care with surgery and radiation would work for many patients, but in the very advanced or high-risk subgroups, many of these tumors would still recur, and [patients would] have poor outcomes at that point. With the advent of immunotherapy, we’ve changed the trajectory for patients who are no longer candidates for surgery and radiation. However, we always want to avoid the worst outcomes whenever possible.
As immunotherapy has evolved, similar to in melanoma, we’re now considering its earlier use in a patient’s treatment journey. [The goal is to show that early intervention can have a significant effect on patient outcomes and that we can balance the risk of toxicity. This represents] the culmination of approximately 8 years of work focused on the highest-risk patients who experience the poorest outcomes when their tumors recur.
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 have 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 have strong data to guide that decision if the clinical situation fits.]
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.]
[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 avoid aggressive interventions later in life? [Those are the key questions for long-term follow-up.]
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.]
[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 have already undergone surgery before discussing immunotherapy. [Now, with an approved indication, we can confidently offer adjuvant cemiplimab in those scenarios to help prevent recurrence.]
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