Neoadjuvant Cemiplimab for Stage II to IV Cutaneous Squamous-Cell Carcinoma

Abstract

Background: In a pilot study involving patients with cutaneous squamous-cell carcinoma, a high percentage of patients had a pathological complete response with the use of two doses of neoadjuvant cemiplimab before surgery. Data from a phase 2 study are needed to confirm these findings.

Methods: We conducted a phase 2, confirmatory, multicenter, nonrandomized study to evaluate cemiplimab as neoadjuvant therapy in patients with resectable stage II, III, or IV (M0) cutaneous squamous-cell carcinoma. Patients received cemiplimab, administered at a dose of 350 mg every 3 weeks for up to four doses, before undergoing surgery with curative intent. The primary end point was a pathological complete response (the absence of viable tumor cells in the surgical specimen) on independent review at a central laboratory, with a null hypothesis that a pathological complete response would be observed in 25% of patients. Key secondary end points included a pathological major response (the presence of viable tumor cells that constitute ≤10% of the surgical specimen) on independent review, a pathological complete response and a pathological major response on investigator assessment at a local laboratory, an objective response on imaging, and adverse events.

Results: A total of 79 patients were enrolled and received neoadjuvant cemiplimab. On independent review, a pathological complete response was observed in 40 patients (51%; 95% confidence interval [CI], 39 to 62) and a pathological major response in 10 patients (13%; 95% CI, 6 to 22). These results were consistent with the pathological responses determined on investigator assessment. An objective response on imaging was observed in 54 patients (68%; 95% CI, 57 to 78). Adverse events of any grade that occurred during the study period, regardless of whether they were attributed to the study treatment, were observed in 69 patients (87%). Grade 3 or higher adverse events that occurred during the study period were observed in 14 patients (18%).

Conclusions: Neoadjuvant therapy with cemiplimab was associated with a pathological complete response in a high percentage of patients with resectable cutaneous squamous-cell carcinoma. (Funded by Regeneron Pharmaceuticals and Sanofi; ClinicalTrials.gov number, NCT04154943.).

Figure 1.. Tumor Response to Neoadjuvant Cemiplimab in Each Patient According to Pathological and Imaging-Based Response Assessment.

Patients with resectable cutaneous squamous-cell carcinoma received cemiplimab, administered at a dose of 350 mg every 3 weeks for up to four doses, before undergoing surgery with curative intent. For each patient, the pathological response to neoadjuvant cemiplimab determined on independent review at a central laboratory is indicated by color coding. The response to neoadjuvant cemiplimab detected on imaging is indicated by the plot, which shows the best percentage change from baseline in the sum of target-lesion diameters on imaging after treatment with neoadjuvant cemiplimab; responses on cross-sectional imaging were defined according to Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1). Data are not shown for the two patients who did not undergo cross-sectional imaging after baseline. The dashed lines indicate imaging-based criteria for partial response (≥30% decrease in the sum of target-lesion diameters) and progressive disease (≥20% increase in the sum of target-lesion diameters). Lesion measurements obtained after disease progression or surgery were excluded. An increase in the sum of target-lesion diameters of more than 100% is reported as 100%. According to RECIST 1.1, regression of 100% on imaging is not required for a complete response in patients with nodal target lesions.

Figure 2.. Clinical Responses in Patients with a Pathological Complete Response to Neoadjuvant Cemiplimab.

Panels A and B show photographs and contrast-enhanced computed tomographic (CT) images obtained from representative patients at baseline and after treatment with four doses of neoadjuvant cemiplimab, administered at a dose of 350 mg every 3 weeks. In Panel A, the patient is an 86-year-old man who presented with stage T4 cutaneous squamous-cell carcinoma involving the right periorbital area. In Panel B, the patient is a 59-year-old woman who presented with stage T3 cutaneous squamous-cell carcinoma involving the right supraorbital area. Neither patient underwent orbital exenteration, because the patients had a partial response on imaging, defined according to RECIST 1.1 and determined on investigator assessment, which allowed for less-extensive surgery.