xRead - An Update on Immunotherapy in Head and Neck Cancer (November 2025)

Adjuvant Cemiplimab in High-Risk Cutaneous SCC

69 patients (16.9%; 36 in the cemiplimab group and 33 in the placebo group) were still receiving cemiplimab or placebo in part 1 of the trial. Efficacy A significant improvement in disease-free sur vival was seen in the cemiplimab group as com pared with the placebo group (24 vs. 65 events; hazard ratio for disease recurrence or death, 0.32; 95% confidence interval [CI], 0.20 to 0.51; P<0.001) (Fig. 1 and Table S3). The Kaplan–Meier curves for the analysis of disease-free survival separated early and remained so for the duration of follow up. The estimated disease-free survival at 24 months was 87.1% (95% CI, 80.3 to 91.6) in the cemiplimab group and 64.1% (95% CI, 55.9 to 71.1) in the placebo group. With regard to the 65 events of disease recur rence or death in the placebo group, 61 patients had disease recurrence and 4 died without disease recurrence; with regard to the 24 events in the cemiplimab group, 18 patients had disease re currence and 6 died without disease recurrence. The disease-free survival benefit with cemipli mab in relevant subgroups is shown in Figure 2. Cemiplimab treatment prolonged freedom from both locoregional and distant recurrences as compared with placebo (Fig. 3 and Table S4). The estimated percentage of patients free from locoregional recurrence at 24 months was 94.6% (95% CI, 89.1 to 97.3) in the cemiplimab group and 76.7% (95% CI, 69.1 to 82.6) in the placebo group. Locoregional recurrence occurred in 9 pa tients in the cemiplimab group and in 40 in the placebo group (hazard ratio, 0.20; 95% CI, 0.09 to 0.40). The estimated percentage of patients free from distant recurrence at 24 months was 94.3% (95% CI, 89.0 to 97.1) in the cemiplimab group and 83.8% (95% CI, 76.3 to 89.0) in the placebo group. Distant recurrence occurred in 10 patients in the cemiplimab group and in 26 in the placebo group (hazard ratio, 0.35; 95% CI, 0.17 to 0.72). Patterns of disease recurrence are provided in Table S5. Exploratory analyses of disease-free survival according to the two dose regimens that were used in this trial appeared to favor cemiplimab over placebo (Table S6). Additional exploratory analy ses showed that the disease-free survival benefit with cemiplimab as compared with placebo ap peared to be maintained regardless of tumoral PD-L1 status (among 85 patients with a PD-L1

tumor proportion score of <1%: 8 vs. 16 events [hazard ratio, 0.32; 95% CI, 0.12 to 0.86]; among 309 patients with PD-L1 tumor proportion score of ≥1%: 14 vs. 45 events [hazard ratio, 0.28; 95% CI, 0.15 to 0.52]) (Fig. S4). Among patients with recurrent disease, the most common subsequent intervention was ce miplimab (Table S7). Among 46 patients who had been originally randomly assigned to the placebo group and received cemiplimab for re current disease in part 2 of the trial, 20 (43%) had an objective radiographic response (Table S8). A total of 25 deaths had occurred as of the data-cutoff date: 12 deaths (4 in the cemiplimab group and 8 in the placebo group) were due to disease progression and 13 deaths (8 in the ce miplimab group and 5 in the placebo group) were due to other causes (Table S9). Overall survival at 2 years was 94.8% (95% CI, 89.6 to 97.4) in the cemiplimab group and 92.3% (95% CI, 86.5 to 95.7) in the placebo group. The hazard ratio for death was 0.86 (95% CI, 0.39 to 1.90), with 51 patients in the placebo group receiving cemipli mab after recurrence (Fig. S5). At a subsequent data-cutoff date of April 7, 2025, there were 33 deaths (15 in the cemiplimab group and 18 in the placebo group), with a hazard ratio of 0.78 (95% CI, 0.39 to 1.56). Safety Adverse events due to any cause during the treat ment period occurred in 91.2% of the patients who received cemiplimab and in 89.2% of those who received placebo (Table 2 and Table S10). The most common adverse events with cemipli mab as compared with placebo were fatigue (in 22.0% vs. 21.6% of the patients), pruritus (in 16.1% vs. 12.3%), rash (in 16.1% vs. 8.8%), and diarrhea (in 15.6% vs. 18.6%). Adverse events of grade 3 or higher that were due to any cause occurred in 23.9% of the patients who received cemiplimab and in 14.2% of those who received placebo. Ad verse events of grade 3 or higher that were con sidered by the investigator to be related to treat ment occurred in 9.8% of patients in the cemiplimab group (Table S11). Adverse events, regardless of attribution, that led to death occurred in two patients in each group (Table 2). One death due to myositis in a patient receiving cemiplimab was considered by the investigator to be related to treatment. Cemiplimab or placebo was discontinued

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