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

The new england journal of medicine

A Overall Survival among Patients with BRAF Mutations

Median Overall Survival (95% CI)

No. of Patients with Event

100 80 90 70 60

3-Yr Estimate (95% CI)

5-Yr Estimate (95% CI)

10-Yr Estimate (95% CI)

68 (58–76)

NR (50.7–NR) 45.5 (26.4–101.2) 24.6 (17.9–31.0) mo

60 (50–69)

Nivo+Ipi (N=103) Nivolumab (N=98) Ipilimumab (N=100)

48 58 73

Nivolumab+Ipilimumab

52 (42–62)

50

56 (45–65)

Nivolumab

37 (27–46)

Hazard ratio for death, nivo+ipi vs. ipilimumab, 0.45 (95% CI, 0.31–0.65) Hazard ratio for death, nivolumab vs. ipilimumab, 0.67 (95% CI, 0.47–0.94) Hazard ratio for death, nivo+ipi vs. nivolumab, 0.67 (95% CI, 0.46–0.98)

46 (36–56)

40 30

37 (28–47)

Percentage of Patients 20

30 (21–39)

Ipilimumab

25 (17–34)

10

0

0 6 12

18

24

30

36 42

48

54

60

66

72

78

84

90

96

102

108

114

120

126

132

Months

Nivo+ipi Nivolumab Ipilimumab No. at Risk

103 98 100

96 85 88

83 75 71

77 67 58

73 57 49

71 55 41

70 52 36

67 47 33

63 44 30

60 42 29

60 41 27

58 40 23

56 39 21

56 38 21

55 38 21

50 34 16

49 32 15

48 29 15

47 29 15

46 27 15

34 23 14

2 0 1

0 0 0

B Overall Survival among Patients without BRAF Mutations

Median Overall Survival (95% CI)

No. of Patients with Event

100 80 90 70 60

3-Yr Estimate (95% CI)

5-Yr Estimate (95% CI)

10-Yr Estimate (95% CI)

39.1 (27.5–84.6) 34.4 (24.1–59.2) 18.5 (14.1–22.7) mo

Nivo+Ipi (N=211) Nivolumab (N=218) Ipilimumab (N=215)

125 134 170

53 (46–59)

48 (41–54)

Nivolumab+Ipilimumab

39 (32–46)

50

49 (42–55)

Hazard ratio for death, nivo+ipi vs. ipilimumab, 0.58 (95% CI, 0.46–0.73) Hazard ratio for death, nivolumab vs. ipilimumab, 0.61 (95% CI, 0.49–0.77) Hazard ratio for death, nivo+ipi vs. nivolumab, 0.95 (95% CI, 0.74–1.21)

40 30

Nivolumab

43 (37–50)

37 (31–44)

32 (26–38)

Percentage of Patients 20

25 (19–31)

Ipilimumab

17 (12–23)

10

0

0 6 12

18

24

30 36 42

48 54 60 66 72 78 84

96 90 102 108 114 120 126

132

Months

Nivo+ipi Nivolumab Ipilimumab No. at Risk

211 218 215

169 180 165

144 156 132

133 134 105

126 124 86

116 116 72

109 106 64

102 98 61

100 97 57

98 95 52

96 93 48

95 90 45

91 87 43

88 85 43

84 80 42

76 73 34

75 70 34

72 69 29

70 67 28

69 65 27

58 54 21

8 4 2

0 0 0

Figure 2. Overall Survival among Patients with or without BRAF Mutations. Panels A and B show Kaplan–Meier estimates of overall survival in the intention-to-treat population among patients with BRAF muta tions and among patients without BRAF mutations, respectively. Symbols (tick marks, triangles, and circles) indicate censored data. Dashed lines indicate the minimum follow-up for the estimate. The widths of the confidence intervals have not been adjusted for multi plicity and should not be used in place of hypothesis testing. For the comparison of nivolumab plus ipilimumab with nivolumab, de scriptive analyses were performed.

ipilimumab, 85% with nivolumab, and 79% with ipilimumab (Fig. 4A), and melanoma-specific survival at 10 years was 96% with nivolumab plus ipilimumab, 97% with nivolumab, and 88% with ipilimumab (Fig. 4B). Among patients who had had at least one grade 3 or 4 treatment-related adverse event (an adverse

event determined by the physician to be related to treatment) within the first 6 months of follow-up, overall survival from 6 months through 10 years was 49% with nivolumab plus ipilimumab, 62% with nivolumab, and 26% with ipilimumab (Fig. S5). In addition, among patients in the nivolu mab-plus-ipilimumab group who had discontin

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n engl j med 392;1 nejm.org January 2, 2025

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