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Table 2. Adverse Events during Treatment Period, According to Grade.*

Cemiplimab (N = 205)

Placebo (N = 204)

Event

Any Grade

Grade ≥3

Any Grade

Grade ≥3

number of patients with event (percent)

Any adverse event

187 (91.2)

49 (23.9)

182 (89.2)

29 (14.2)

Serious adverse event

36 (17.6)

31 (15.1)

19 (9.3)

14 (6.9)

Adverse event leading to discontinuation of cemiplimab or placebo

20 (9.8)

16 (7.8)

3 (1.5)

2 (1.0)

Adverse event leading to death†

2 (1.0)

2 (1.0)

2 (1.0)

2 (1.0)

Adverse events in ≥10% of the patients in either group‡ Fatigue

45 (22.0)

1 (0.5)

44 (21.6)

0

Pruritus

33 (16.1)

1 (0.5)

25 (12.3)

0

Rash

33 (16.1)

1 (0.5)

18 (8.8)

0

Diarrhea

32 (15.6)

3 (1.5)

38 (18.6)

0

Arthralgia

26 (12.7)

0

25 (12.3)

0

Hypothyroidism

24 (11.7)

1 (0.5)

6 (2.9)

0

Maculopapular rash

23 (11.2)

0

12 (5.9)

0

Bowen’s disease

16 (7.8)

1 (0.5)

21 (10.3)

2 (1.0)

* Shown are adverse events that developed or worsened during the treatment period and any adverse events that were considered by the investigator to be related to cemiplimab or placebo that occurred during the posttreatment period but before part 2 of the trial (subsequent cemiplimab treatment). † One death due to pneumonia was considered by the investigator to be unrelated to cemiplimab, and one death due to myositis was considered by the investigator to be related to cemiplimab. One death due to pneumonia and one death due to new primary malignant lung neoplasm were both considered by the investigator to be unrelated to placebo. ‡ Patients were counted only once according to the worst grade for multiple occurrences within a preferred term.

(start at every 3 weeks, with a switch to every 6 weeks). The trial results indicated that both regimens prolonged disease-free survival and had similar safety profiles. Findings from the POST/TROG 05.01 trial 6 were key determinants in defining the high-risk criteria and categories for the C-POST trial. The current trial was successful in defining a popu lation of patients at high risk for recurrence of cutaneous squamous-cell carcinoma as evidenced by an estimated 3-year disease-free survival of approximately 60% in the placebo group, which closely matched the predicted disease-free sur vival that was based on data from the POST/TROG 05.01 trial. The results reported here will help to inform future updates to consensus staging cri teria, as well as aid in the identification of patients in the clinic who are at the highest risk for disease recurrence. Another phase 3 trial of adjuvant anti–PD-1 therapy in high-risk cutaneous squamous-cell

carcinoma was the KEYNOTE-630 trial of adju vant pembrolizumab (ClinicalTrials.gov number, NCT03833167). That trial was stopped for futil ity after a prespecified analysis, according to a press release from the sponsor. 19 Publication of the results of the KEYNOTE-630 trial is awaited and may provide information about why the trial did not show an improvement with pembroli zumab with regard to the primary end point. In this trial, adjuvant cemiplimab therapy led to a large benefit, as compared with placebo, with regard to disease-free survival among patients at high risk for recurrence of cutaneous squamous cell carcinoma. Supported by Regeneron Pharmaceuticals and Sanofi. Dr. Rischin was supported in part by a National Health and Medical Research Council Investigator Grant (APP1175929). Disclosure forms provided by the authors are available with the full text of this article at NEJM.org. A data sharing statement provided by the authors is available with the full text of this article at NEJM.org. We thank the trial participants, their families, and the trial site staff; Anusha Dandu, M.S., Grace Fletchman, B.A., Fionnuala

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