Table 1.
Main characteristics of the included articles
| Study | PD-1or PD-L1 | irAE grade | irAE type | HR for PFS (95%CI) | HR for OS (95%CI) | Model | Design |
|---|---|---|---|---|---|---|---|
| Kim 2017 | Nivolumab Pembrolizumab | 1–2 | Thyroid dysfunction | 0.38 (0.17–0.85) | 0.11 (0.01–0.92) | M | RC |
| Osorio [13] | Pembrolizumab | 1–3 | Thyroid dysfunction | 0.58 (0.27–1.21) | 0.29 (0.09–0.94) | U | PC |
| Haratani 2017 | Nivolumab | 1–4 | Any irAE | 0.542 (0.295–0.971) | 0.285 (0.102–0.675) | M | RC |
| 1–4 | Skin | 0.476 (0.232–0.912) | 0.209 (0.049–0.618) | ||||
| 1–4 | Endocrine | 0.237 (0.037–0.842) | 0.504 (0.027–2.629) | ||||
| Grangeon 2018 | Anti-PD-L1 or anti-PD-1 | Any grade | Any irAE | 0.42 (0.32–0.57) | 0.29 (0.18–0.46) | U | RC |
| Any grade | Pneumonitis | 1.19 (0.52–2.70) | 1.42 (0.45–4.54) | ||||
| Any grade | Colitis | 0.73 (0.35–1.50) | 0.24 (0.03–1.73) | ||||
| Any grade | Hepatitis | 0.97 (0.45–2.08) | 0.97 (0.30–3.08) | ||||
| Any grade | Thyroiditis | 0.58 (0.39–0.85) | 0.46 (0.25–0.86) | ||||
| Toi [7] | Nivolumab or pembrolizumab | 1–4 | Any irAE | 0.45 (0.30–0.68) | 0.42 (0.24–0.71) | U | RC |
| Sato [14] | Nivolumab | 1–4 | Any irAE | 0.28 (0.04–1.46) | U | RC | |
| Ricciuti [22] | Nivolumab | 1–4 | Any irAE | 0.48 (0.34–0.67) | 0.38 (0.26–0.56) | M | RC |
| 1–4 | Lung | 0.56 (0.33–0.96) | 0.46 (0.24–0.89) | ||||
| 1–4 | Gastrointestinal | 0.52 (0.3–0.9) | 0.5 (0.26–0.98) | ||||
| 1–4 | Endocrine | 0.59 (0.4–0.89) | 0.45 (0.28–0.72) | ||||
| 1–4 | Skin | 0.57 (0.35–0.95) | 0.8 (0.46–1.39) | ||||
| 1–4 | Hepatobiliary | 0.72 (0.41–1.42) | 0.94 (0.53–1.66) | ||||
| Ksienski [20] | Nivolumab and pembrolizumab | 1–2 | Any irAE | 0.85 (0.50–1.42) | M | ||
| > 3 | Any irAE | 2.29 (1.05–4.98) | |||||
| Nivolumab | 1–2 | Any irAE | 0.74 (0.41–1.31) | ||||
| ≥ 3 | Any irAE | 2.53 (1.15–5.57) | |||||
| Lesueur [19] | Nivolumab | 1–4 | Any irAE | 0.660 (0.433–1.099) | 0.64 (0.377–1.087) | M | RC |
| Lisberg [16] | Pembrolizumab | 1–4 | Any irAE | 0.62 (0.40–0.96) | 0.72 (0.49–1.05) | M | RC |
| Fujimoto [17] | Nivolumab | ≥ 3 | Any irAE | 0.76 (0.55–1.01) | M | ||
| 1–4 | Pneumonitis | 0.71 (0.52–0.97) | M | RC | |||
| Cortellini [24] | Anti-PD-1 | 1–4 | Any irAE | 0.59 (0.47–0.76) | 0.55 (0.41–0.72) | M | RC |
| 3–4 | Any irAE | 0.75 (0.51–1.11) | 0.76 (0.48–1.21) | M | |||
| 1–4 | Endocrine | 0.63 (0.45–0.89) | 0.55 (0.37–0.83) | M | |||
| 1–4 | Skin | 0.46 (0.31–0.69) | 0.43 (0.27–0.70) | M | |||
| 1–4 | Gastrointestinal | 0.68 (0.47–1.01) | 0.61 (0.38–0.98) | OS: M PFS: U | |||
| 1–4 | Pneumonitis | 1.20 (0.76–1.92) | 1.32 (0.79–2.19) | U | |||
| 1–4 | Hepatobiliary | 1.47 (0.72–1.96) | 1.09 (0.48–2.45) | U | |||
| Ahn, [25] | Nivolumab or pembrolizumab | 1–4 | Any irAE | 0.434 (0.256–0.735) | 0.484 (0.255–0.919) | M | RC |
| 1–2 | Skin | 0.643 (0.350–1.180) | 0.42 (0.162–1.087) | ||||
| 1–4 | Endocrine | 0.368 (0.132–1.028) | 0.255 (0.051–1.288) | ||||
| 1–4 | Pneumonitis | 1.686 (0.618–4.579) | 4.177 (1.420–11.942) | ||||
| Berner [26] | Anti-PD-1 | NA | Skin | 0.22 (0.09–0.49) | 0.29 (0.12–0.71) | U | PC |
| Bjørnhart 2019 | ICI | 3–4 | Any irAE | 0.71 (0.39–1.27) | 0.47 (0.21–1.05) | U | RC |
| Imai 2019 | Embrolizumab | 1–4 | Any irAE | 0.70 (0.35–1.37) | 0.78 (0.28–1.37) | U | RC |
| Baldini [28] | Nivolumab | 1–4 | Any irAE | 1.44 (1.22–1.71) | M | RC | |
| Ksienski [29] | Pembrolizumab or nivolumab | 1–5 | Any irAE | 1.37 (0.91–2.08) | M | RC | |
| Sugano [30] | Nivolumab, pembrolizumab or atezolizumab | 1–4 | ILD | 0.39 (0.19–0.77) | M | RC | |
| Naqash [31] | Nivolumab | Any | Any irAE | 0.69 (0.55–0.87) | 0.62 (0.55–1.03) | M | RC |
| Any | Thyroid dysfunction | 0.98 (0.67–1.42) | 0.79 (0.53–1.19) | U | |||
| Any | Pneumonitis | 1.36 (0.91–2.02) | 1.35 (0.89–2.02) | U | |||
| Any | Hepatitis | 0.75 (0.45–1.31) | 1.18 (0.63–1.97) | U | |||
| Any | Colitis/diarrhea | 0.65 (0.35–1.21) | 0.65 (0.35–1.21) | U | |||
| Any | Musculoskeletal | 0.31 (0.04–1.87) | 0.37 (0.11–1.17) | U | |||
| Any | Skin | 0.55 (0.34–0.87) | 0.67 (0.41–1.07) | OS: U PFS: M | |||
| Yamaguchi [32] | Pembrolizumab or nivolumab | Any grade | Any irAE | 0.73 (0.48–1.09) | 0.83 (0.51–1.32) | U | RC |
| Cortellini [33] | Pembrolizumab | Any | Any irAE | 0.49 (0.39–0.61) | 0.41 (0.31–0.53) | M | RC |
| 3–4 | Any irAE | 0.78 (0.57–1.05) | 0.70 (0.48–1.03) | U | |||
| Any | Cutaneous | 0.72 (0.51–1.01) | 0.48 (0.30–0.78) | M | |||
| Any | Endocrine | 0.40 (0.27–0.59) | 0.30 (0.17–0.52) | M | |||
| Any | Gastrointestinal | 0.58 (0.39–0.86) | 0.67 (0.42–1.07) |
OS: U PFS: M |
|||
| Any | Hepatic | 1.31 (0.83–2.06) | 0.82 (0.43–1.54) | U | |||
| Any | Pulmonary | 0.65 (0.39–1.09) | 0.59 (0.30–1.14) | U | |||
| Any | Rheumatlogic | 0.50 (0.29–0.87) | 0.47 (0.23–0.96) | M | |||
| Any | Neuro-muscular | 0.50 (0.18–1.34) | 0.52 (0.16–1.62) | U | |||
| Noguchi [34] | Pembrolizumab | Any grade | Any irAE | 0.33 (0.17–0.65) | M | RC | |
| Kubo [35] | Nivolumab/pembrolizumab | Any grade | Any irAE | 1.59 (0.93–2.71) | U | ||
| ≥ 2 | Any irAE | 1.18 (0.70–1.99) | U | RC |
OS overall survival, PFSprogression-free survival, M multivariate, U univariate, RCretrospective cohort, PC prospective cohort