(a) Analysis of age-specific pooled hazard ratios and 95%CI of overall survival for younger patients assigned to intervention treatment, compared with those assigned to control treatment, by subgroup

Analysis	N	Random-effects model		Fixed-effects model		Heterogeneity
		HR (95% CI)	P	HR (95% CI)	P	I2	P
Class of immune checkpoint inhibitor	12	0.75 (0.65, 0.87)	≤0.001	0.80 (0.75, 0.86)	≤0.001	75.1%	≤0.001
PD-1/PD-L1	10	0.71 (0.60, 0.84)	≤0.001	0.76 (0.70, 0.82)	≤0.001	72.2%	≤0.001
CTLA-4	2	0.95 (0.73, 1.25)	0.718	0.97 (0.84, 1.13)	0.731	67.7%	0.079
Type of immune checkpoint inhibitor	10	0.75 (0.63, 0.90)	0.001	0.81 (0.75, 0.87)	≤0.001	78.4%	≤0.001
Nivolumab	3	0.79 (0.53, 1.18)	0.249	0.82 (0.69, 0.98)	0.028	79.2%	0.008
Pembrolizumab	3	0.54 (0.42, 0.68)	≤0.001	0.55 (0.46, 0.66)	≤0.001	42.0%	0.178
Atezolizumab	2	0.85 (0.75, 0.95)	0.005	0.85 (0.75, 0.95)	0.005	0.0%	0.641
Ipilimumab	2	0.95 (0.73, 1.25)	0.718	0.97 (0.84, 1.13)	0.731	67.7%	0.079
Pathology	12	0.75 (0.65, 0.87)	≤0.001	0.80 (0.75, 0.86)	≤0.001	75.1%	≤0.001
Small cell lung cancer	2	1.04 (0.88, 1.23)	0.613	1.04 (0.88, 1.23)	0.613	0.0%	0.441
Non-small cell lung cancer	10	0.71 (0.60, 0.83)	≤0.001	0.76 (0.70, 0.82)	≤0.001	71.6%	≤0.001
Histotype	5	0.62 (0.47, 0.81)	≤0.001	0.66 (0.58, 0.76)	≤0.001	72.1%	0.006
Squamous	3	0.63 (0.45, 0.88)	0.006	0.68 (0.56, 0.81)	≤0.001	64.9%	0.058
Non-squamous	2	0.60 (0.32, 1.11)	0.102	0.64 (0.52, 0.79)	≤0.001	88.2%	0.004
Line	12	0.75 (0.65, 0.87)	≤0.001	0.80 (0.75, 0.86)	≤0.001	75.1%	≤0.001
First-line	5	0.89 (0.71, 1.12)	0.329	0.94 (0.84, 1.06)	0.332	66.8%	0.017
Subsequent line	7	0.67 (0.56, 0.81)	≤0.001	0.74 (0.68, 0.80)	≤0.001	72.0%	0.002
Masking	12	0.75 (0.65, 0.87)	≤0.001	0.80 (0.75, 0.86)	≤0.001	75.1%	≤0.001
Double-blind	6	0.71 (0.53, 0.95)	0.022	0.80 (0.71, 0.90)	≤0.001	83.0%	≤0.001
Open-label	6	0.78 (0.66, 0.93)	0.005	0.80 (0.73, 0.87)	≤0.001	65.8%	0.012