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

Nivolumab plus Ipilimumab in Advanced Melanoma

A Melanoma-Specific Survival among Patients with BRAF Mutations

Median Melanoma

100 80 90 70 60

3-Yr Estimate (95% CI)

5-Yr Estimate (95% CI)

10-Yr Estimate (95% CI)

No. of Patients with Event

Specific Survival (95% CI)

70 (60–78)

62 (52–71)

Nivolumab+Ipilimumab

NR (70.7–NR) 58.7 (35.9–NR) 28.1 (18.1–34.4) mo

56 (46–65)

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

43 51 69

60 (49–69)

50

49 (38–59)

40 30

Nivolumab

42 (31–52)

Hazard ratio for death from melanoma, nivo+ipi vs. ipilimumab, 0.42 (95% CI, 0.29–0.62) Hazard ratio for death from melanoma, nivolumab vs. ipilimumab, 0.62 (95% CI, 0.43–0.89) Hazard ratio for death from melanoma,

39 (29–49)

31 (22–41)

Percentage of Patients 20

Ipilimumab

27 (18–36)

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

nivo+ipi vs. nivolumab, 0.68 (95% CI, 0.45–1.02)

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 Melanoma-Specific Survival among Patients without BRAF Mutations

Median Melanoma

100 80 90 70 60

3-Yr Estimate (95% CI)

5-Yr Estimate (95% CI)

10-Yr Estimate (95% CI)

No. of Patients with Event

Specific Survival (95% CI)

114.9 (37.4–NR) 41.2 (31.2–NR) 19.9 (16.2–25.6) mo

59 (52–65)

55 (48–62)

Nivolumab+Ipilimumab

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

96 112 152

50 (42–57)

50

53 (46–59)

49 (42–55)

Nivolumab

40 30

45 (38–52)

Hazard ratio for death from melanoma, nivo+ipi vs. ipilimumab, 0.51 (95% CI, 0.40–0.66) Hazard ratio for death from melanoma, nivolumab vs. ipilimumab, 0.58 (95% CI, 0.46–0.75) Hazard ratio for death from melanoma,

35 (28–41)

29 (23–35)

Percentage of Patients 20

Ipilimumab

22 (16–28)

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

nivo+ipi vs. nivolumab, 0.88 (95% CI, 0.67–1.15)

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 3. Melanoma-Specific Survival among Patients with or without BRAF Mutations. Panels A and B show Kaplan–Meier estimates of melanoma-specific survival in the intention-to-treat population among patients with BRAF mutations and among patients without BRAF mutations, respectively. Melanoma-specific survival was an exploratory end point. 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 multiplicity and should not be used in place of hypothesis testing. For the comparison of nivolumab plus ipilimumab with nivolumab, descriptive analyses were performed.

ued treatment during the induction phase because of a treatment-related adverse event, overall sur vival from 6 months through 10 years was 43% and melanoma-specific survival from 6 months through 10 years was 50% (Fig. S6). Among patients who had received immune-modulating medication within the first 6 months of follow

up, melanoma-specific survival from 6 months through 10 years was 59% with nivolumab plus ipilimumab, 53% with nivolumab, and 27% with ipilimumab (Table S9). Among patients who had not received immune-modulating medication within the first 6 months, melanoma-specific survival from 6 months through 10 years was

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

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