Table 3.
Pooled incidence of trAE in combination epidermal growth receptor tyrosine kinase inhibitors and immune checkpoint inhibitors versus tyrosine kinase inhibitor monotherapy.
| trAEs | Combination of TKI and ICI | TKI Monotherapy | Odds Ratio (Combined vs. Monotherapy) | p |
|---|---|---|---|---|
| Overall | ||||
| Any grade | 100.0 (96.3, 100.0) a,b | 87.7 (68.1, 99.0) b,c | 1.27 (0.75, 1.66) | 0.077 |
| Grade ≥ 3 | 30.0 (12.0, 51.6) b,c | 13.8 (0.1, 40.4) b,c | 1.23 (0.85, 1.76) | 0.271 |
| Skin | ||||
| Any grade | 61.1 (47.3, 74.1) a | 42.6 (25.5, 61.2) c | 1.19 (0.95, 1.49) | 0.012 |
| Grade ≥ 3 | 1.7 (0.0, 8.5) a | 0.2 (0.0, 0.9) a | 1.13 (0.96, 1.29) | 0.082 |
| Gastrointestinal | ||||
| Any grade | 44.0 (21.2, 68.1) c | 40.3 (22.5, 59.5) c | 1.04 (0.77, 1.40) | 0.790 |
| Grade ≥ 3 | 3.6 (0.0, 11.6) a | 1.0 (0.2, 2.1) a | 1.13 (0.99, 1.02) | 0.076 |
| Interstitial lung disease (ILD) | ||||
| Any grade | 16.3 (6.7, 28.6) a | 2.8 (1.5, 4.3) a | 1.28 (1.11, 1.48) | 0.001 |
| Grade ≥ 3 | 4.4 (0.8, 9.8) a | 0.5 (0.0, 1.5) a | 1.16 (1.05, 1.28) | 0.003 |
| Sensitivity analysis (on studies of sample size >40) | ||||
| Any grade | 30.5 (23.1, 38.3) a | 3.4 (2.0, 5.0) a | 1.48 (1.34, 1.62) | < 0.001 |
| Grade ≥ 3 | 9.6 (2.7, 23.1) a | 1.0 (0.3, 2.1) a | 1.24 (1.06, 1.45) | 0.007 |
ICI, immune checkpoint inhibitor; TKI, tyrosine kinase inhibitor; trAE, treatment-related adverse events. a Estimated from fixed effect model. b Results from Nie et al. [47] were not included into calculation as overall trAEs were not reported. c Estimated from random effects model due to heterogeneity.