FLEX November 2023

The new england journal of medicine

vestigator assessment, was 47% (95% CI, 21 to 73) among patients with PD-L1 expression in less than 1% of tumor cells, as compared with 76% (95% CI, 60 to 88) among those with PD-L1 expression in 1% of tumor cells or more (Table S9). Among the 50 patients with samples that could be assessed for tumor mutational burden at baseline, the median tumor mutational bur den was 58.5 mutations per megabase (inter quartile range, 31.3 to 92.2) (Table S10). The median tumor mutational burden was 61.1 mu tations per megabase among the 28 patients who had a pathological response (19 patients with a pathological complete response and 9 pa tients with a pathological major response), as compared with 46.2 mutations per megabase among the 22 patients who had no pathological complete response or pathological major re sponse. However, given the wide range of values observed among both patients who had a patho logical response and those who did not, no cor relations can be made between efficacy and tu mor mutational burden (Fig. S4). The percentage of patients who had a pathological complete re sponse was 56% (95% CI, 35 to 76) among pa tients with a high tumor mutational burden, as compared with 20% (95% CI, 7 to 41) among those with a low tumor mutational burden (Ta ble S11). The percentage of patients who had an objective response on imaging was 80% (95% CI, 59 to 93) among patients with a high tumor mutational burden, as compared with 56% (95% CI, 35 to 76) among those with a low tumor mutational burden (Table S12). Discussion Neoadjuvant cemiplimab, administered at a dose of 350 mg every 3 weeks for up to four doses before surgery with curative intent, was associ ated with a pathological complete response in 51% of patients with stage II, III, or IV (M0) cutaneous squamous-cell carcinoma. On imaging based response assessment, with responses de fined according to RECIST 1.1 and determined on investigator assessment, an objective re sponse was observed in 68% of patients. Overall, the percentage of patients with a pathological response was similar to the percentage of pa tients with a response on imaging, and the vast majority of patients who had a partial response on imaging were found to have a pathological

A Stage T4 Tumor Involving the Right Periorbital Area Baseline

After Four Doses of Cemiplimab

B Stage T3 Tumor Involving the Right Supraorbital Area

Baseline

After Four Doses of Cemiplimab

Figure 2. Clinical Responses in Patients with a Pathological Complete Response to Neoadjuvant Cemiplimab. Panels A and B show photographs and contrast-enhanced computed tomo graphic (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 in volving 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 ex enteration, 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.

PD-L1 expression in 1% of tumor cells or more (PD-L1–positive). Pathological responses were observed in both PD-L1–negative and PD-L1– positive patients, but the percentage of patients who had a pathological complete response was lower among patients with PD-L1 expression in less than 1% of tumor cells (20%; 95% CI, 4 to 48) than among those with PD-L1 expression in 1% of tumor cells or more (54%; 95% CI, 37 to 69) (Table S8). The percentage of patients who had an objective response on imaging, defined according to RECIST 1.1 and determined on in

1564

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

The New England Journal of Medicine Downloaded from nejm.org on October 30, 2023. For personal use only. No other uses without permission. Copyright © 2022 Massachusetts Medical Society. All rights reserved.