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

Pembrolizumab in Head and Neck Cancer

A CPS-10 Population

and 59.2% (95% CI, 51.7 to 65.9) in the control group (hazard ratio for death, 0.72; 95% CI, 0.52 to 0.98; two-sided P = 0.04) (Fig. 2A). Because the protocol-specified criterion for statistical sig nificance was not met, subsequent overall sur vival hypotheses were not formally tested at this time. In the CPS-1 population, the estimated overall survival at 3 years was 69.0% (95% CI, 63.3 to 74.0) in the pembrolizumab group and 60.2% (95% CI, 54.1 to 65.8) in the control group, (hazard ratio for death, 0.72; 95% CI, 0.56 to 0.94) (Fig. 2B). In the total population, the estimated overall survival at 3 years was 68.4% (95% CI, 62.9 to 73.3) and 61.1% (95% CI, 55.1 to 66.5), respectively (hazard ratio for death, 0.76; 95% CI, 0.59 to 0.98) (Fig. 2C). Safety The as-treated population included 361 partici pants in the pembrolizumab group and 315 in the control group. The median total duration of therapy was 9.1 months (range, 0.03 to 22.3) and 2.9 months (range, 0.03 to 7.2), respectively (Table S5A). The median duration of adjuvant pembrolizumab was 9.7 months (range, 0.03 to 18.9), with a median of 15.0 cycles (range, 1.0 to 16.0) (Table S5C). In accordance with the trial design, adverse events were recorded from ran Event-free survival was defined as the time from ran domization to the first occurrence of disease progres sion or recurrence according to Response Evaluation Criteria in Solid Tumors, version 1.1, or death from any cause. Panel A shows Kaplan–Meier estimates of event-free survival among all randomly assigned par ticipants who had tumors with a programmed death li gand 1 (PD-L1) combined positive score (CPS) of 10 or more. The CPS was defined as the number of PD-L1– staining cells, including tumor cells, lymphocytes, and macrophages, divided by the total number of viable tumor cells, multiplied by 100. Panel B shows Kaplan– Meier estimates of event-free survival among all ran domly assigned participants who had tumors with a PD-L1 CPS of 1 or more. Panel C shows Kaplan–Meier estimates of event-free survival among all randomly assigned participants. Participants in the pembroliz umab group were assigned to receive neoadjuvant and adjuvant pembrolizumab in addition to standard care; adjuvant pembrolizumab was planned to start concomi tantly with postoperative radiotherapy or chemoradio therapy. Participants in the control group were as signed to receive standard care. Tick marks indicate censored data. Figure 1. Event-free Survival as Assessed by Central Review.

100

80 90 70 60 50 40 30 20 10

74.0

65.1

59.8

Pembrolizumab

60.0

53.2

45.9

Control

Hazard ratio for progression, recurrence, or death, 0.66 (95% CI, 0.49–0.88) P=0.004 (two-sided)

Event-free Survival (%)

0

0

6

12

18

24

30

36

42

48

54

60 66

Months

No. at Risk

Pembrolizumab Control

234 231

188 168

154 115

128 94

111 70

93 53

61 38

40 27

27 18

19 9

2 3

0 0

B CPS-1 Population

100

80 90 70 60 50 40 30 20 10

74.8

64.6

58.2

Pembrolizumab

61.3

53.4

44.9

Control

Hazard ratio for progression, recurrence, or death, 0.70 (95% CI, 0.55–0.89) P=0.003 (two-sided)

Event-free Survival (%)

0

0

6

12

18

24

30

36

42

48

54

60 66

Months

No. at Risk

Pembrolizumab Control

347 335

274 245

220 170

181 140

147 104

122 82

83 56

51 36

33 25

21 15

2 7

0 0

C Total Population

100

80 90 70 60 50 40 30 20 10

75.1

65.0

57.6

62.5

Pembrolizumab

54.6

46.4

Control

Hazard ratio for progression, recurrence, or death, 0.73 (95% CI, 0.58–0.92) P=0.008 (two-sided)

Event-free Survival (%)

0

48

18

0

6

12

24

30

36

42

54

60 66

Months

No. at Risk

34 25

Pembrolizumab Control

363 351

287 258

232 183

191 147

157 110

129 88

88 59

55 37

21 15

2 7

0 0

domization to 30 days after treatment discon tinuation and serious adverse events were re corded from randomization to 90 days after treatment discontinuation, which substantially

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n engl j med 393;1 nejm.org July 3, 2025

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