Table 1.
Main characteristics of the included studies.
| Study | Design | ICIs types | Landmark analysis | irAEs types | irAEs grade | ORR (irAEs vs non-irAEs) | OS Hazard ratio (95%CI) | PFS Hazard ratio (95%CI) |
|---|---|---|---|---|---|---|---|---|
| Osorioet al. (9) | Retrospective | P | no | Thyroid dysfunction | 1–3 | NA | 0.29 (0.09–0.94) | 0.58 (0.27–1.21) |
| Teraoka et al. (10) | Prospective | N | 6-week | Global | 1–2 | 33.3%/12.5% | NA | NA |
| Kim et al. (11) | Retrospective | N/P | no | Thyroid dysfunction | 1–2 | 31.6%/10.3% | 0.11 (0.01–0.92) | 0.38 (0.17–0.85) |
| Sato et al. (12) | Retrospective | N | no | Global | 1–4 | 63.6%/7.4% | NA | 0.10 (0.02–0.37) |
| Lisberg et al. (13) | Retrospective | P | no | Global | 1–4 | NA | 0.75 (0.58–0.96) | 0.75 (0.56–0.99) |
| Haratani et al. (14) | Retrospective | N | 6-week | Global Skin Endocrine |
1–4 | 52.3%/27.9% | 0.285 (0.102–0.675) 0.209 (0.049–0.618) 0.504 (0.027–2.629) |
0.542 (0.295–0.971) 0.476 (0.232–0.912) 0.237 (0.037–0.842) |
| Owen et al. (15) | Retrospective | NA | no | Global | 1–5 | NA | 0.364 (0.203–0.649)* | NA |
| Grangeon et al. (16) | Retrospective | NA | no | Global Pneumonitis Thyroiditis Colitis Hepatitis |
1–5 | 23.1%/5.7% | 0.29 (0.18–0.46) 1.42 (0.45–4.54) 0.46 (0.25–0.86) 0.24 (0.03–1.73) 0.97 (0.3–3.08) |
0.42 (0.32–0.57) 1.19 (0.52–2.70) 0.58 (0.39–0.85) 0.73 (0.35–1.50) 0.97 (0.45–2.08) |
| Ricciuti et al. (17) | Retrospective | N | no | Global Lung Gastrointestinal Endocrine Skin Hepatobiliary |
1–4 | 43.5%/10% | 0.38 (0.26–0.56) 0.46 (0.24–0.89) 0.5 (0.26–0.98) 0.45 (0.28–0.72) 0.8 (0.46–1.39) 0.94 (0.53–1.66) |
0.48 (0.34–0.67) 0.56 (0.33–0.96) 0.52 (0.3–0.9) 0.59 (0.4–0.89) 0.57 (0.35–0.95) 0.72 (0.41–1.24) |
| Cortellini et al. (18) | Retrospective | NA | 6-week | Global Endocrine Skin Gastrointestinal Hepatic |
1–4 | 46.5%/25.7% | 0.53 (0.41–0.69) 0.55 (0.37–0.83) 0.43 (0.27–0.70) 0.61 (0.38–0.98) 1.09 (0.48–2.45) |
0.57 (0.45–0.72) 0.63 (0.45–0.89) 0.46 (0.31–0.69) 0.68 (0.47–1.01) 1.47 (0.72–2.96) |
| Toi et al. (19) | Retrospective | N/P | no | Global | 1–4 | 51.5%/12.7% | 0.42 (0.24–0.71) | 0.45 (0.30–0.68) |
| Ahn et al. (20) | Retrospective | N/P | 6-week | Global Skin Endocrine Pneumonitis |
1–4 | 41.2%/26.7% | 0.484 (0.255–0.919) 0.420 (0.162–1.087) 0.255 (0.051–1.288) 4.117 (1.420–11.942) |
0.434 (0.256–0.735) 0.643 (0.350–1.180) 0.368 (0.132–1.028) 1.686 (0.618–4.597) |
| Berner et al. (21) | Prospective | N/P | no | Skin | NA | 60%/14.6% | 0.29 (0.12–0.71) | 0.22 (0.09–0.49) |
| Fukihara et al. (22) | Retrospective | N/P | 8-week | Pneumonitis | 1–5 | 42.9%/25.4% | NA | NA |
| Baldini et al. (23) | Retrospective | N | no | Global | 1–4 | 27.2%/16.5% | 0.69 (0.58–0.82)* | 0.69 (0.6–0.79)* |
| Cui et al. (24) | Retrospective | N/P/A/D | no | Pneumonitis | 1–4 | 61.9%/29.9% | NA | NA |
| Naqash et al. (25) | Retrospective | N | no | Global Thyroid Pneumonitis Hepatitis Colitis/diarrhea Skin |
NA | NA | 0.65 (0.52–0.8) 0.79 (0.53–1.19) 1.35 (0.89–2.02) 1.18 (0.63–1.97) 0.65 (0.35–1.21) 0.67 (0.41–1.07) |
0.69 (0.55–0.87) 0.98 (0.67–1.42) 1.36 (0.91–2.02) 0.75 (0.45–1.31) 0.65 (0.35–1.21) 0.57 (0.36–0.88) |
| Serrano et al. (26) | Retrospective | NA | no | Global | 1–3 | NA | 0.53 (0.31–0.93) | 0.44 (0.26–0.73) |
| Akamatsu et al. (27) | Retrospective | NA | no | Global | NA | 48.4%/10.7% | 0.45 (0.11–1.88) | 0.30 (0.10–0.85) |
| Pawel et al. (28) | Retrospective | A | no | Global | 1–4 | NA | 0.79 (0.60–1.05) | NA |
| Hosoya et al. (29) | Prospective | N | 2-week | Global Rash Diarrhea |
1–4 | 60.9%/12.8% | 0.92 (0.47–1.79) | 0.6 (0.36–0.99) 0.57 (0.33–0.99) 1.08 (0.46–2.5) |
| Boussageon et al. (30) | Retrospective | NA | 12-week | Global | 1–3 | NA | NA | 0.33 (0.14–0.76) |
| Sosa et al. (31) | Retrospective | NA | no | Global | NA | NA | 0.18 (0.06–0.53) | NA |
| Rizzi et al. (32) | Retrospective | NA | 6-week | Global | 3–4 | 47.9%/30.0% | NA | NA |
| Aso et al. (33) | Retrospective | N/P | 6-week | Skin | 1–3 | 72.0%/24.0% | 0.75 (0.4–1.43) | 0.58 (0.33–0.99) |
| Riudavets et al. (34) | Retrospective | NA | 2.4-month | Global Rash Endocrine |
1–5 | 48.6%/23.2% | 0.32 (0.22–0.46) 0.42 (0.23–0.75) 0.59 (0.34–1) |
0.43 (0.28–0.64) |
| Kubo et al. (35) | Retrospective | NA | no | Global | NA | NA | NA | 0.43 (0.24–0.76) |
| Lim et al. (36) | Retrospective | N | no | Global | 1–4 | 31.6%/11.3% | 0.5 (0.33–0.76) | NA |
| Noguchi et al. (37) | Retrospective | P | no | Global | 1–4 | NA | NA | 0.33 (0.17–0.65) |
| Sugano et al. (38) | Retrospective | N/P/A | no | ILD | NA | 62.5%/20.9% | NA | 0.39 (0.19–0.77) |
| Usui et al. (40) | Retrospective | N | 8-week | Skin rash | NA | 22.2%/20.8% | NA | 0.435 (0.105–1.196) |
| Ahmed et al. (39) | Retrospective | N/P | no | Thyroid | NA | NA | NA | 0.38 (0.2–0.71) |
| Bjørnhart et al. (41) | Retrospective | N/P | no | Global | 3–4 | NA | 0.47 (0.21–1.05) | 0.71 (0.39–1.27) |
| Ksienski et al. (42) | Retrospective | N/P | 6-week | Global | ≥3 | NA | 2.29 (1.05–4.98) | NA |
irAEs, immune-related adverse events; ORR, objective response rate; OS, overall survival; PFS, progression-free survival; CI, confidence interval; NA, not available; N, nivolumab; P, pembrolizumab; A, atezolizumab; D, durvalumab; ILD, interstitial lung disease.
*The HR and 95% CI was calculated through taking reciprocal.