Analysis | N | Random-effects model | Fixed-effects model | Heterogeneity | |||
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HR (95% CI) | P | HR (95% CI) | P | I2 | 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 |
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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 |
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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 |
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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 |
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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 |
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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.