Table 2.
The results for the association of antibiotics use and efficacy of immune checkpoint inhibitors.
| N | Hazard ratio | P for hazard ratio | Heterogeneity (P, I2) | Publication bias | |
|---|---|---|---|---|---|
| Overall survival | |||||
| Overall | 17 | 2.37(2.05–2.75) | < 0.001 | 0.851, 0.0% | Begg’s Test = 0.401; Egger’s test = 0.235 |
| Time of antibiotics use | |||||
| Before ICI initiation | 10 | 2.29(1.92–2.73) | < 0.001 | 0.837, 0.0% | Begg’s Test = 1.000; Egger’s test = 0.975 |
| One month before ICI initiation | 7 | 2.23(1.82–2.74) | < 0.001 | 0.865, 0.0% | Begg’s Test = 0.711; Egger’s test = 0.778 |
| Two month before ICI initiation | 2 | 1.97(1.49–2.59) | < 0.001 | 0.199, 38.0% | Begg’s Test = 1.000; Egger’s test = / |
| Before or after ICI initiation | 7 | 2.56(1.96–3.36) | < 0.001 | 0.572, 0.0% | Begg’s Test = 0.266; Egger’s test = 0.207 |
| Cancer type | |||||
| Non-small-cell lung cancer | 10 | 2.68(2.19–3.28) | < 0.001 | 0.911, 0.0% | Begg’s Test = 0.283; Egger’s test = 0.105 |
| Urothelial carcinoma | 2 | 2.01(1.23–3.29) | 0.005 | 0.778, 0.0% | Begg’s Test = 1.000; Egger’s test = / |
| Renal cell carcinoma | 2 | 1.68(1.00–2.83) | 0.052 | 0.518, 0.0% | Begg’s Test = 1.000; Egger’s test = / |
| ICI drug | |||||
| Anti-PD-1 | 12 | 2.45(2.04–2.97) | < 0.001 | 0.765, 0.0% | Begg’s Test = 0.669; Egger’s test = 0.316 |
| Anti-PD-1/CTLA-4/PD-1+ CTLA-4 | 3 | 2.23(1.68–2.97) | < 0.001 | 0.910, 0.0% | Begg’s Test = 0.734; Egger’s test = 0.398 |
| Treatment type | |||||
| ICI monotherapy | 5 | 2.90(1.80–4.68) | < 0.001 | 0.861, 0.0% | Begg’s Test = 0.806; Egger’s test = 0.494 |
| Sample size | |||||
| <100 | 6 | 2.97(1.98–4.44) | < 0.001 | 0.779, 0.0% | Begg’s Test = 1.000; Egger’s test = 0.617 |
| ≥100 | 11 | 2.29(1.95–2.68) | < 0.001 | 0.780, 0.0% | Begg’s Test = 0.855; Egger’s test = 0.983 |
| Country | |||||
| Asia | 3 | 2.12(1.46–3.07) | < 0.001 | 0.695, 0.0% | Begg’s Test = 1.000; Egger’s test = 0.647 |
| No-Asia | 14 | 2.41(2.06–2.84) | < 0.001 | 0.768, 0.0% | Begg’s Test = 0.499; Egger’s test = 0.323 |
| Progression-free survival | |||||
| Overall | 15 | 1.84(1.49–2.26) | < 0.001 | 0.002, 56.2% | Begg’s Test = 0.091; Egger’s test = 0.035 |
| Time of antibiotics use | |||||
| Before ICI initiation | 8 | 1.70(1.43–2.02) | < 0.001 | 0.178, 30.1% | Begg’s Test = 0.466; Egger’s test = 0.421 |
| Before or after ICI initiation | 8 | 1.91(1.31–2.78) | 0.001 | 0.001, 68.8% | Begg’s Test = 0.175; Egger’s test = 0.066 |
| Cancer type | |||||
| Non-small-cell lung cancer | 9 | 1.79(1.29–2.49) | < 0.001 | 0.001, 69.3% | Begg’s Test = 0.602; Egger’s test = 0.176 |
| Renal cell carcinoma | 2 | 2.12(1.51–2.96) | < 0.001 | 0.815, 0.0% | Begg’s Test = 1.000; Egger’s test = / |
| ICI drug | |||||
| Anti-PD-1 | 10 | 1.92(1.43–2.58) | < 0.001 | 0.003, 61.8% | Begg’s Test = 0.436; Egger’s test = 0.190 |
| Anti-PD-1/CTLA-4/PD-1+ CTLA-4 | 3 | 1.63(1.13–2.36) | 0.009 | 0.092, 53.4% | Begg’s Test = 0.734; Egger’s test = 0.317 |
| Treatment type | |||||
| ICI monotherapy | 5 | 1.94(1.20–3.13) | 0.007 | 0.076, 52.7% | Begg’s Test = 0.221; Egger’s test = 0.081 |
| Sample size | |||||
| <100 | 7 | 1.96(1.51–2.54) | < 0.001 | 0.157, 35.5% | Begg’s Test = 0.764; Egger’s test = 0.391 |
| ≥100 | 8 | 1.76(1.34–2.32) | < 0.001 | 0.002, 65.3% | Begg’s Test = 0.210; Egger’s test = 0.098 |
| Country | |||||
| Asia | 2 | 2.67(1.66–4.27) | < 0.001 | 0.271, 17.5% | Begg’s Test = 1.000; Egger’s test = / |
| No-Asia | 13 | 1.75(1.41–2.18) | < 0.001 | 0.004, 55.9% | Begg’s Test = 0.138; Egger’s test = 0.070 |
NOTE, CTLA-4: Cytotoxic T-Lymphocyte-associated Antigen 4; I:2 Degree of Heterogeneity; ICI: Immune Checkpoint Inhibitors; PD-1: Programmed cell death Drotein-1; PD-L1: Programmed cell Death-Ligand 1; “/”: Not applicable because Egger’s test cannot be performed when the number of studies was 2