Table 1.
Main characteristics of the eligible studies
| Study | Cancer type | Agents | Exposed group/ total, No. | irAE type | irAE grade | Hazard ratio (95% CI) | Landmark analysis | Model | Design |
|---|---|---|---|---|---|---|---|---|---|
| Sanlorenzo, 2015 [32] | Multiple | P | 19/43a | Skin | 1–3 |
PFS: 0.82 (0.17–4.06) PFS: 0.70 (0.05–9.50) PFS: 0.12 (0.02–0.74) |
No | M | RC |
| 7/24b | 1–3 | ||||||||
| 9/16c | 1 | ||||||||
| Keller, 2016 [9] | Melanoma | N | 67/143 | Rash | 1–3 | OS: 0.423 (0.243–0.735) | 12 weeks | M | RC |
| 50/143 | Pneumonitis | 1–2 | OS: 0.371 (0.022–6.313) | ||||||
| 19/143 | Vitiligo | 1–2 | OS: 0.184 (0.036–0.940) | ||||||
| 16/143 | Hypothyroidism | 1–2 | OS: 0.360 (0.100–1.291) | ||||||
| 9/143 | Mucositis | 1–2 | OS: 0.087 (0.005–1.448) | ||||||
| 3/143 | Diarrhea/colitis | 1–3 | OS: 0.632 (0.348–1.149) | ||||||
| 2/143 | Hyperthyroidism | 1–2 | OS: 1.604 (0.420–6.118) | ||||||
| N.A./143 | Myalgias | 1–2 | OS: 0.377 (0.022–6.477) | ||||||
| Haratani, 2017 [10] | NSCLC | N |
OS: 46/130 PFS: 44/105 |
Global | 1–4 |
OS: 0.285 (0.102–0.675) PFS: 0.542 (0.295–0.971) |
6 weeks | M | RC |
|
OS: 31/130 PFS: 31/105 |
Skin | 1–4 |
OS: 0.209 (0.049–0.618) PFS: 0.476 (0.232–0.912) |
||||||
|
OS: 6/130 PFS: 6/105 |
Endocrine | 1–4 |
OS: 0.504 (0.027–2.629) PFS: 0.237 (0.037–0.842) |
||||||
| Kim, 2017 [11] | NSCLC | N/P | 19/58 | Thyroid dysfunction | 1–2 |
OS: 0.11 (0.01–0.92) PFS: 0.38 (0.17–0.85) |
No | M | RC |
| Judd, 2017 [23] | Multiple | N/P | N.A./173 | Global | 1–2 | OS: 0.480 (0.227–1.107) d | No | M | RC |
| Osorio, 2017 [12] | NSCLC | P | 10/48 | Thyroid dysfunction | 1–3 |
OS: 0.29 (0.09–0.94) PFS: 0.58 (0.27–1.21) |
No | U | PC |
| Nakamura, 2017 [22] | Melanoma | N | 9/35 | Vitiligo | 1–2 |
OS: 0.16 (0.03–0.79) PFS: 0.58 (0.27–1.21) |
No | U | RC |
| Grangeon, 2018 [14] | NSCLC | N/P | 124/270 | Global | 1–4 |
OS: 0.29 (0.18–0.46) PFS: 0.42 (0.32–0.57) |
No | U | RC |
| 53/270 | Thyroiditis | 1–4 |
OS: 0.46 (0.25–0.86) PFS: 0.58 (0.39–0.85) |
||||||
| 11/270 | Colitis | 1–4 |
OS: 0.24 (0.03–1.73) PFS: 0.73 (0.35–1.50) |
||||||
| 8/270 | Hepatitis | 1–4 |
OS: 0.97 (0.30–3.08) PFS: 0.94 (0.45–2.08) |
||||||
| 6/270 | Pneumonitis | 1–4 |
OS: 1.42 (0.45–1.54) PFS: 1.19 (0.52–2.7) |
||||||
| Toi, 2018 [18] | NSCLC | N/P | 66/137 | Global | 1–4 |
OS: 0.42 (0.24–0.71) PFS: 0.45 (0.30–0.68) |
No | U | RC |
| Sato, 2018 [31] | NSCLC | N | 11/18e | Global | 1–4 | PFS: 0.28 (0.04–1.46) | 60 days | U | RC |
| Rogado, 2018 [25] | Multiple | N/P | 40/106 | Global | 1–4 |
OS: 0.909 (0.625–1.429)f PFS: 0.435 (0.278–0.714)f |
No | M | RC |
| Ricciuti, 2018 [15] | NSCLC | N | 85/195 | Global | 1–4 |
OS: 0.38 (0.26–0.56) PFS: 0.48 (0.34–0.67) |
No | M | RC |
| 39/195 | Endocrine | 1–2 | |||||||
|
OS: 0.59 (0.40–0.89) PFS: 0.46 (0.24–0.89) | |||||||||
| 32/195 | Hepatobiliary | 1–4 |
OS: 0.94 (0.53–1.66) PFS: 0.72 (0.41–1.24) |
||||||
| 21/195 | Skin | 1–4 |
OS: 0.80 (0.46–1.39) PFS: 0.57 (0.35–0.95) |
||||||
| 17/195 | Gastrointestinal | 1–4 |
OS: 0.52 (0.30–0.90) PFS:0.50 (0.26–0.98) |
||||||
| 16/195 | Lung | 1–4 |
PFS: 0.45 (0.28–0.72) OS: 0.56 (0.33–0.96) |
||||||
| Ksienski, 2018 [24] | NSCLC | N/P | 91/246 | Global | 1–2 | OS: 0.85 (0.50–1.42) | 6 weeks | M | RC |
| 25/180 | ≥3 | OS: 2.29 (1.05–4.98) | |||||||
| Faje, 2018 [8] | Melanoma | I | 64/281 | Hypophysitis | N.A. | OS: 0.53 (0.36–0.75) | No | U | RC |
| Indini, 2018 [4] | Melanoma | N/P | 102/173 | Global | 1–5 |
OS: 0.39 (0.18–0.81) PFS: 0.47 (0.26–0.86) |
No | M | RC |
| Lesueur, 2018 [26] | NSCLC | N | 62/104 | Global | 1–4 |
OS: 0.640 (0.377–1.087) PFS: 0.660 (0.433–1.099) |
No | M | RC |
| Owen, 2018 [5] | NSCLC | N/P/A | 27/91 | Global | 1–4 | OS: 0.364 (0.203–0.649)f | No | U | RC |
| Lisberg, 2018 [27] | NSCLC | P | 28/97 | Global | 1–4 |
OS: 0.72 (0.49–1.05) PFS: 0.62 (0.40–0.96) |
No | M | RC |
| Fujimoto, 2018 [30] | NSCLC | N | 68/613 | Global | ≥3 | PFS: 0.76 (0.55–1.01) | No | M | RC |
| 62/613 | Pneumonitis | 1–4 | PFS: 0.71 (0.52–0.97) | ||||||
| Okada, 2019 [6] | Melanoma | N | 8/15 | Global | 1–2 | OS: 0.01 (0.00011–0.88) | No | M | RC |
| Lei, 2019 [16] | Multiple | N/P | 34/103 | Thyroiditis | 1–4 |
OS: 0.40 (0.19–0.85) PFS: 0.45 (0.27–0.76) |
No | U | RC |
| Cortellini, 2019 [19] | NSCLC | N/P | 224/524 | Global | 1–4 |
OS: 0.55 (0.41–0.72) PFS: 0.59 (0.47–0.76) |
6 weeks | M | RC |
| 50/559 | 3–4 |
OS: 0.53 (0.41–0.69) PFS: 0.75 (0.51–1.11) |
No | M | |||||
| 78/559 | Endocrine | 1–4 |
OS: 0.55 (0.37–0.83) PFS: 0.63 (0.45–0.89) |
No | M | ||||
| 59/559 | Skin | 1–4 |
OS: 0.43 (0.27–0.70) PFS: 0.46 (0.31–0.69) |
No | M | ||||
| 51/559 | Gastrointestinal | 1–4 |
OS: 0.61 (0.38–0.98) PFS: 0.68 (0.47–1.01) |
No |
OS: M PFS: U |
||||
| 23/559 | Pneumonitis | 1–4 |
OS: 1.32 (0.79–2.19) PFS: 1.20 (0.76–1.92) |
No | U | ||||
| 10/559 | Hepatic | 1–4 |
OS: 1.09 (0.48–2.45) PFS: 1.47 (0.72–2.96) |
No | U | ||||
| Ahn, 2019 [21] | NSCLC | N/P |
OS: 55/133 PFS: 51/111 |
Global | 1–4 |
OS: 0.484 (0.255–0.919) PFS: 0.434 (0.256–0.735) |
6 weeks | M | RC |
|
OS: 26/133 PFS: 24/133 |
Skin | 1–2 |
OS: 0.420 (0.162–1.087) PFS: 0.643 (0.350–1.180) |
||||||
|
OS: 14/133 PFS: 14/111 |
Endocrine | 1–4 |
OS: 0.255 (0.051–1.288) PFS: 0.368 (0.132–1.028) |
||||||
|
OS: N.A./133 PFS: N.A./111 |
Pneumonitis | 1–4 |
OS: 4.177 (1.420–11.942) PFS: 1.686 (0.618–4.597) |
||||||
| Berner, 2019 [20] | NSCLC | N/P | 48/83 | Skin | N.A. |
OS: 0.29 (0.12–0.71) PFS: 0.22 (0.09–0.39) |
No | U | PC |
| Verzoni, 2019 [7] | RCC | N | 77/389 | Global | 1–4 | OS: 0.57 (0.35–0.93) | No | M | RC |
| Yamauchi, 2019 [13] | Multiple | N |
OS: 67/191 PFS: 61/175 |
Thyroid | N.A. |
OS: 0.61 (0.39–0.93) PFS: 0.66 (0.46–0.95) |
No | U | RC |
| Bjørnhart, 2019 [28] | NSCLC | N/P | 25/112 | Global | 3–4 |
OS: 0.47 (0.21–1.05) PFS: 0.71 (0.39–1.27) |
No | U | RC |
| Ishihara, 2019 [17] | RCC | N | 23/47 | Global | 1–4 | PFS: 0.25 (0.11–0.56) | No | M | RC |
| Moel, 2019 [33] | Melanoma | I | 81/133 e | Global | 1–4 | OS: 1.12 (0.7–1.79) | No | U | RC |
| Lang, 2019 [29] | Melanoma | I | 29/100 | Diarrhea | 1–3 |
OS: 1.32 (0.71–2.44) PFS: 1.40 (0.88–2.22) |
No | U | RC |
| 7/100 | Diarrhea | 3 |
OS: 2.15 (0.76–6.07) PFS: 1.96 (0.89–4.32) |
Abbreviations: irAE immune-related adverse event, NSCLC non-small-cell lung carcinoma, RCC renal cell carcinoma, Multiple multiple cancer types, RC retrospective cohort, PC prospective cohort, N nivolumab, P pembrolizumab, A atezolizumab, I ipilimumab, N.A. not available, OS overall survival, PFS progression-free survival, M multivariate, U univariate
aThe patients group receiving a dose of 10 mg/kg every 3 weeks
bThe patients group receiving a dose of 10 mg/kg every 2 weeks
cThe patients group receiving a dose of 2 mg/kg every 3 weeks
dThe 95% CI was calculated according to the HR and p value
eThe sample size was estimated from the manuscript
fThe HR and 95% CI was calculated through taking reciprocal