FLEX November 2023

Neoadjuvant Cemiplimab for Squamous-Cell Carcinoma

100

Pathological complete response

Pathological major response

No pathological complete response or pathological major response

No pathological evaluation

80

60

Progressive disease on imaging

40

20

0

−20

Partial response on imaging

−40

−60

−80

of Target-Lesion Diameters on Imaging

−100

Best Percentage Change from Baseline in the Sum

Patients

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 patho logical 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 neo adjuvant 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-sec tional 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 diame ters). 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.

most common being fatigue (22 patients [28%]), maculopapular rash (11 patients [14%]), and diar rhea (9 patients [11%]) (Table S6). Immune-related adverse events occurred in 12 patients (15%) who received neoadjuvant cemiplimab, including grade 3 immune-related adverse events in 3 pa tients (4%) (Table S7). Four adverse events that occurred during the study period were fatal. A fatal exacerbation of congestive heart failure occurred in a 93-year-old woman after two doses of cemiplimab. In that patient, coexisting medical conditions at base line included congestive heart failure (grade 2), paroxysmal atrial fibrillation (grade 2), coronary artery disease, bilateral carotid-artery stenosis, hypercholesterolemia, and hypertension. The ex acerbation of congestive heart failure was fatal despite treatment with glucocorticoids. This death was considered by the investigator to be possibly related to treatment. The three other fatal adverse events were con

sidered by the investigator to be unrelated to treatment. First, an 85-year-old man had a fatal acute myocardial infarction after three doses of cemiplimab. Coexisting medical conditions at baseline included peripheral vascular disease and coronary artery disease. Second, a 73-year-old man had disease progression after one dose of cemiplimab and had a fatal myocardial infarc tion approximately 7 weeks after that dose. Co existing medical conditions at baseline included heart failure, atrial fibrillation, and type 2 dia betes. Third, an 82-year-old man died from pneumonia associated with coronavirus disease 2019 in the postoperative period. Biomarker Analyses Of the 79 patients included in the study, 56 had samples that could be assessed for the PD-L1 tumor proportion score at baseline. Of these patients, 15 had PD-L1 expression in less than 1% of tumor cells (PD-L1–negative) and 41 had

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n engl j med 387;17 nejm.org october 27, 2022

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