Comparison of Immune Checkpoint Inhibitors between Older and Younger Patients with Advanced or Metastatic Lung Cancer: A Systematic Review and Meta-Analysis

Table 2

(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	I^2	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

(b) Analysis of age-specific pooled hazard ratios and 95%CI of overall survival for older 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	I^2	P
Class of immune checkpoint inhibitor	12	0.81 (0.72, 0.92)	0.001	0.82 (0.76, 0.90)	≤0.001	48.8%	0.015
PD-1/PD-L1	10	0.76 (0.67, 0.87)	≤0.001	0.76 (0.69, 0.84)	≤0.001	37.1%	0.094
CTLA-4	2	1.02 (0.86, 1.21)	0.783	1.02 (0.87, 1.21)	0.777	0.7%	0.388
Type of immune checkpoint inhibitor	10	0.80 (0.69, 0.93)	0.003	0.82 (0.74, 0.89)	≤0.001	53.4%	0.009
Nivolumab	3	0.83 (0.59, 1.18)	0.304	0.82 (0.67, 0.99)	0.042	60.9%	0.037
Pembrolizumab	3	0.72 (0.59, 0.88)	0.001	0.72 (0.59, 0.88)	0.001	0.0%	0.782
Atezolizumab	2	0.66 (0.47, 0.91)	0.013	0.70 (0.58, 0.83)	≤0.001	60.2%	0.113
Ipilimumab	2	1.02 (0.86, 1.21)	0.783	1.02 (0.87, 1.21)	0.777	0.7%	0.388
Pathology	12	0.81 (0.72, 0.92)	0.001	0.82 (0.76, 0.90)	≤0.001	58.8%	0.015
Small cell lung cancer	2	0.76 (0.45, 1.29)	0.313	0.86 (0.70, 1.05)	0.132	81.8%	0.004
Non-small cell lung cancer	10	0.82 (0.72, 0.92)	0.001	0.82 (0.74, 0.90)	≤0.001	33.9%	0.111
Histotype	5	0.79 (0.64, 0.98)	0.030	0.80 (0.69, 0.93)	0.003	47.2%	0.066
Squamous	3	0.87 (0.65, 1.17)	0.347	0.89 (0.74, 1.07)	0.207	53.9%	0.070
Non-squamous	2	0.66 (0.52, 0.84)	0.001	0.66 (0.52, 0.84)	0.001	0.0%	0.678
Line	12	0.81 (0.72, 0.92)	0.001	0.82 (0.76, 0.90)	≤0.001	48.8%	0.015
First-line	5	0.87 (0.71, 1.07)	0.193	0.92 (0.81, 1.04)	0.182	59.0%	0.023
Subsequent line	7	0.76 (0.66, 0.86)	≤0.001	0.76 (0.68, 0.85)	≤0.001	19.0%	0.274
Masking	12	0.81 (0.72, 0.92)	0.001	0.82 (0.76, 0.90)	≤0.001	48.8%	0.015
Double-blind	6	0.80 (0.66, 0.98)	0.029	0.84 (0.75, 0.95)	0.007	57.9%	0.020
Open-label	6	0.81 (0.69, 0.97)	0.018	0.80 (0.72, 0.90)	≤0.001	43.4%	0.089

NoteFoot. The p value for heterogeneity is from the I² test comparing the interaction HRs across subgroups including class of ICI, type of ICI, pathology, histotype, line of treatment, masking method, and represents heterogeneity within each subgroup. PD-1/PD-L1= programmed cell death-1/ programmed cell death-Ligand 1. CTLA4=cytotoxic T-lymphocyte protein 4.