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PARIS -- Neoadjuvant therapy with cemiplimab (Libtayo) achieved deep pathologic responses in patients with resectable cutaneous squamous cell carcinoma (cSCC), according to research presented here.

Among 79 patients treated with the PD-1 inhibitor, 40 experienced a pathologic complete response (51%, 95% CI 39-62) on independent review, while another 10 had a pathological major response (13.3%, 95% CI 6-22), reported Neil Gross, MD, of MD Anderson Cancer Center in Houston.

The combined pathologic response rate of 63% in this group of patients is the highest observed in a multicenter anti-PD-1 neoadjuvant monotherapy study for any solid tumor type, said Gross during a session at the annual congress of the European Society for Medical Oncology (ESMO). "Clearly, immunotherapy is highly effective in the neoadjuvant setting in this disease."

Results from this study were published concurrently in the .

Gross reported that responses on imaging were similarly high, "but with the caveat that most of these were partial imaging responses."

Specifically, an objective response on imaging was observed in 54 patients (68%, 95% CI 57-78). However, a complete response on imaging was only seen in five patients (6%), with 49 having a partial response. Thus, the percentage of patients with a complete response on imaging was much lower than the percentage of patients with a pathological complete response on independent review.

"I think this underscores the need for histologic confirmation of response, still," Gross said. "Hopefully, we'll have biomarkers in the future that can help better direct us."

Despite being early data, "it is very promising," said ESMO discussant Christian Blank, MD, PhD, of the Netherlands Cancer Institute in Amsterdam and the Leiden University Medical Center in the Netherlands. "Maturation is needed to learn whether [pathologic response rate] in cutaneous squamous cell carcinoma is also a surrogate marker for event-free survival."

This enrolled patients with resectable stage II-IV cSCC in Australia, Germany, and the U.S. These patients had a median age of 73 years, and 85% were male. Most patients (76%) had an ECOG score of 0 and had stage III (48%) or stage IV disease (46%). Forty-seven patients (60%) presented with nodal metastases.

After a screening period of up to 28 days, patients received neoadjuvant cemiplimab administered intravenously at a dose of 350 mg every 3 weeks for up to four doses over a 12-week period, before undergoing surgery with curative intent.

Sixty-two patients received all four doses, and 70 patients underwent surgery. Of the nine patients who did not have surgery, three declined because imaging showed their cancer responded to the immunotherapy, two were lost to follow-up or non-compliance, two had progressive disease, and two experienced adverse events.

Of the 70 patients who proceeded to surgery, five had a complete response, 44 had a partial response, and 16 had stable disease on imaging. The five patients with a complete response on imaging were also found to have a pathological complete response. Of those patients with a partial response on imaging, 30 (68%) were found to have a pathological complete response, eight (18%) were found to have a pathological major response, and six (14%) were found to have no pathological complete response or pathological major response.

Regarding safety, adverse events (AEs) of any grade were observed in 87% of patients, most commonly fatigue, diarrhea, nausea, and maculopapular rash. Grade 3 or higher AEs were observed in 17% of patients.

Four adverse events that occurred during the study period were fatal, one of which -- an exacerbation of congestive heart failure in a 93-year-old woman -- was considered to be possibly treatment related.

Gross and his colleagues said that, while the study provides a rationale for neoadjuvant cemiplimab in patients with resectable cSCC, questions remain. For example, which patients can avoid radiation and/or surgery? And which patients are most likely to respond to immunotherapy?

Another question concerned the number of doses of cemiplimab necessary to achieve a response. "Do we really need four doses of cemiplimab?" Blank asked. "Can we also achieve the same result with two doses?"

Gross noted that two doses were used in a pilot trial. "That's because we thought that's what patients and surgeons would tolerate, not expecting as dramatic a response," he said. "But because we saw several patients who had major pathologic responses -- near complete responses -- we thought pushing it to four doses may increase the number of complete pathologic responses."

"Ultimately, I'm not sure of the right answer," Gross said.

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