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

Pembrolizumab in Head and Neck Cancer

A CPS-10 Population

extended the monitoring window for the pem brolizumab group. Treatment-related adverse events of any grade occurred in 81.4% of the participants in the pembrolizumab group and 81.9% of those in the control group; events of grade 3 or higher oc curred in 44.6% and 42.9%, respectively (Table 3). In both groups, the most common treatment related adverse event of grade 3 or higher was stomatitis (11.6% in the pembrolizumab group and 13.3% in the control group) (Table S6). Treatment-related serious adverse events oc curred in 19.1% of the participants in the pem brolizumab group and 10.5% of those in the control group (Table 3 and Table S7); serious adverse events of any cause occurred in 49.6% and 36.8%, respectively (Table S8). Deaths at tributed to treatment-related adverse events oc curred in four participants (1.1%) in the pembro lizumab group (one each from renal failure, coronavirus disease 2019–related pneumonia, pneumonitis, and unknown cause) and one par ticipant (0.3%) in the control group (acute kid ney injury). Treatment-related adverse events led to treat ment discontinuation in 17.7% of the partici pants in the pembrolizumab group and 12.4% of those in the control group (Table 3 and Table S9). The most common event leading to discon tinuation of radiotherapy was stomatitis in the pembrolizumab group (0.7%) and an increased alanine aminotransferase level in the control group (0.4%); the most common event leading to discontinuation of cisplatin was decreased neu trophil count in both groups (5.6% and 7.2%, Figure 2. Overall Survival. Overall survival was defined as the time from random ization to death from any cause. Panel A shows Kaplan– Meier estimates of overall survival among all randomly assigned participants who had tumors with a PD-L1 CPS of 10 or more. Panel B shows Kaplan–Meier esti mates of overall survival among all randomly assigned participants who had tumors with a PD-L1 CPS of 1 or more. Panel C shows Kaplan–Meier estimates of over all survival among all randomly assigned participants. Participants in the pembrolizumab group were assigned to receive neoadjuvant and adjuvant pembrolizumab in addition to standard care; adjuvant pembrolizumab was planned to start concomitantly with postoperative radiotherapy or chemoradiotherapy. Participants in the control group were assigned to receive standard care. Tick marks indicate censored data.

100

85.8

80 90 70 60 50 40 30 20 10

74.8

68.2

77.8

Pembrolizumab

67.1

59.2

Control

Hazard ratio for death, 0.72 (95% CI, 0.52–0.98) P=0.04 (two-sided)

Overall Survival (%)

0

0

6

12

18

24

30

36

42

48

54

60 66

Months

No. at Risk

Pembrolizumab Control

234 231

218 205

191 173

161 142

143 113

120 91

89 74

70 56

47 40

32 25

22 17

0 1

B CPS-1 Population

100

86.3

80 90 70 60 50 40 30 20 10

75.3

69.0

77.5

Pembrolizumab

67.3

60.2

Control

Hazard ratio for death, 0.72 (95% CI, 0.56–0.94)

Overall Survival (%)

0

0

6

12

18

24

30

36

42

48

54

60 66

Months

No. at Risk

Pembrolizumab Control

347 335

325 296

283 247

237 203

201 161

170 135

132 103

100 76

68 55

45 36

29 26

0 1

C Total Population

100

86.7

80 90 70 60 50 40 30 20 10

75.9

68.4

77.9

Pembrolizumab

67.9

61.1

Control

Hazard ratio for death, 0.76 (95% CI, 0.59–0.98)

Overall Survival (%)

0

48

18

0

6

12

24

30

36

42

54

60 66

Months

No. at Risk

70 57

Pembrolizumab Control

363 351

340 311

298 261

250 212

214 169

179 142

138 109

104 81

46 38

30 27

0 2

respectively); and the most common event leading to discontinuation of pembrolizumab was pneu monitis (1.9%). Treatment-related adverse events that occurred in at least 1% of the participants in

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

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