FLEX November 2023

The new england journal of medicine

(lower than the median tumor mutational bur den). Details regarding the exploratory analyses are provided in the Supplementary Appendix. Statistical Analysis We estimated that a sample of 72 patients would provide the study with at least 90% power to reject the null hypothesis — that a pathological complete response would be observed in 25% of patients, a percentage that is not clinically meaningful — at a two-sided significance level of 0.05. This estimate was based on the assump tion that a pathological complete response would be observed in 44% of the patients. The planned sample size was increased by 5%, to 76 patients, to account for the possibility that pa tients might prematurely withdraw from the study. The null hypothesis could be ruled out on the basis of the lower limit of the exact 95% confidence interval if a pathological complete response was observed in at least 37% of the patients. The percentages of patients with a pathological complete response, a pathological major response (with the definition excluding patients with a pathological complete response), and an objective response on imaging and as sociated exact 95% confidence intervals were calculated with the use of the Clopper–Pearson method. The primary analysis was performed when all patients had completed surgery or were no lon ger deemed to be candidates for surgery after treatment with neoadjuvant cemiplimab. The efficacy and safety of cemiplimab were assessed in all patients who received at least one dose of the study treatment. All the reported data are based on a data-cutoff date of December 1, 2021, the date on which the final patient completed the 1-month follow-up visit after surgery. Patients From March 20, 2020, to July 8, 2021, a total of 79 patients began to receive the study treatment (Fig. S2). Characteristics of the patients at base line are summarized in Table 1. The median age was 73 years (range, 24 to 93), and 67 patients (85%) were men. The predominant primary ana tomical site of the tumor was the head and neck (72 patients [91%]). Most patients had an ECOG performance-status score of 0 (60 patients [76%]) Results

Table 1. Characteristics of the 79 Patients at Baseline.*

Characteristic

Value

Median age (range) — yr

73 (24–93)

Male sex — no. (%)

67 (85)

Race — no. (%)† White

69 (87)

Other

2 (3)

Not reported

8 (10)

Not Hispanic or Latinx — no. (%)†

74 (94)

Primary tumor site — no. (%) Head and neck

72 (91)

Trunk, arms, and legs

7 (9)

Stage group — no. (%)‡ II

5 (6)

III

38 (48)

IV (M0)

36 (46)

Tumor stage at screening — no. (%)‡ TX

23 (29)

Tis

1 (1)

T1

4 (5)

T2

10 (13)

T3

39 (49)

T4a

2 (3)

Node stage at screening — no. (%)‡ NX

1 (1)

N0

31 (39)

N1

13 (16)

N2§

11 (14)

N2b

9 (11)

N2c

1 (1)

N3¶

1 (1)

N3a

1 (1)

N3b

11 (14)

ECOG performance-status score — no. (%)‖ 0

60 (76)

1

19 (24)

* Percentages may not total 100 because of rounding. † Race and ethnic group were reported by the patient.

‡ Tumor–node–metastasis (TNM) staging of cutaneous squamous-cell carci noma with involvement of the head and neck was based on the eighth edition of the American Joint Committee on Cancer Staging Manual , and TNM staging of cutaneous squamous-cell carcinoma without involvement of the head and neck was based on the ninth edition of the Union for International Cancer Control Manual of Clinical Oncology . § These values were not further specified as N2a, N2b, or N2c. ¶ These values were not further specified as N3a or N3b. ‖ Scores on the Eastern Cooperative Oncology Group (ECOG) performance status scale range from 0 to 5, with higher scores indicating greater disability.

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

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