Table 3.

Median overall survival in 12‐week landmark analysisa subgroups

Characteristic	Mo (95% CI)	HR (95% CI)	p value
Age
<60 yr	32 (25–49)	Ref
≥60 yr	31 (24–39)	1.07 (0.68 – 1.68)	.765
Gender
Male	32 (24–41)	Ref
Female	35 (25–40)	0.81 (0.51–1.27)	.356
BRAF statusb
Wild‐type	29 (23–38)	Ref
Mutant	41 (28–77)	0.63 (0.37–1.08)	.095
LDH
Normal	38 (31–73)	Ref
Elevated	22 (17–28)	2.25 (1.43–3.54)	<.001
Primary sitec
Cutaneous	34 (25–40)	Ref
Noncutaneous	27 (22–39)	1.12 (0.68–1.83)	.663
M staged
0/1a	Not reached	Ref
1b	30 (20–32)	2.82 (1.4–5.67)	.004
1c	23 (19–39)	2.49 (1.27–4.88)	.008
1de	39 (25–68)	1.72 (0.81–3.69)	.161
Line of anti‐PD‐1
1	27 (23–NR)	Ref
2	27 (20–41)	0.89 (0.49–1.64)	.710
3	38 (26–73)	0.65 (0.37–1.12)	.122
≥4	68 (23–NR)	0.51 (0.19–1.37)	.180
Any irAE
No	23 (16–32)	Ref
Yes	39 (30–100)	0.46 (0.3–0.72)	.001
Grade ≥3 irAE
No	29 (24–38)	Ref
Yes	Not reached	0.35 (0.15–0.81)	.015
Objective irAE onlyf
No	25 (22–34)	Ref
Yes	46 (30–100)	0.45 (0.26–0.77)	.003

^aA total of 43 patients were excluded from the landmark analysis for dying within 12 weeks of anti‐PD‐1 checkpoint blockade to eliminate poor prognosis bias.

^bBRAF mutations include V600E/Ec/D/K/R.

^cSee supplemental online Table 1 for primary site subcategories.

^dAmerican Joint Committee on Cancer 2017 melanoma staging classification. Five patients had unresectable stage III (M0) and were included with M1a for statistical analysis.

^eA total of 12 (33%) of patients with brain metastases died before the 12‐week landmark and were thus excluded, the most of any M stage group (see supplemental online Table S2).

^fIncludes hepatotoxicity, pancreatitis, hypo‐ and hyperthyroid, hypophysitis or adrenal insufficiency, hyperglycemia, pneumonitis, and myositis.

Abbreviations: CI, confidence interval; HR, hazard ratio; irAE, immune‐related adverse event; LDH, lactate dehydrogenase; NR, not reached; PD‐1, programmed cell death protein 1.