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Table 1 Main characteristics of the eligible studies

From: Are immune-related adverse events associated with the efficacy of immune checkpoint inhibitors in patients with cancer? A systematic review and meta-analysis

StudyCancer typeAgentsExposed group/ total, No.irAE typeirAE gradeHazard ratio (95% CI)Landmark analysisModelDesign
Sanlorenzo, 2015 [32]MultipleP19/43aSkin1–3PFS: 0.82 (0.17–4.06)
PFS: 0.70 (0.05–9.50)
PFS: 0.12 (0.02–0.74)
NoMRC
7/24b1–3
9/16c1
Keller, 2016 [9]MelanomaN67/143Rash1–3OS: 0.423 (0.243–0.735)12 weeksMRC
50/143Pneumonitis1–2OS: 0.371 (0.022–6.313)
19/143Vitiligo1–2OS: 0.184 (0.036–0.940)
16/143Hypothyroidism1–2OS: 0.360 (0.100–1.291)
9/143Mucositis1–2OS: 0.087 (0.005–1.448)
3/143Diarrhea/colitis1–3OS: 0.632 (0.348–1.149)
2/143Hyperthyroidism1–2OS: 1.604 (0.420–6.118)
N.A./143Myalgias1–2OS: 0.377 (0.022–6.477)
Haratani, 2017 [10]NSCLCNOS: 46/130
PFS: 44/105
Global1–4OS: 0.285 (0.102–0.675)
PFS: 0.542 (0.295–0.971)
6 weeksMRC
OS: 31/130
PFS: 31/105
Skin1–4OS: 0.209 (0.049–0.618)
PFS: 0.476 (0.232–0.912)
OS: 6/130
PFS: 6/105
Endocrine1–4OS: 0.504 (0.027–2.629)
PFS: 0.237 (0.037–0.842)
Kim, 2017 [11]NSCLCN/P19/58Thyroid dysfunction1–2OS: 0.11 (0.01–0.92)
PFS: 0.38 (0.17–0.85)
NoMRC
Judd, 2017 [23]MultipleN/PN.A./173Global1–2OS: 0.480 (0.227–1.107) dNoMRC
Osorio, 2017 [12]NSCLCP10/48Thyroid dysfunction1–3OS: 0.29 (0.09–0.94)
PFS: 0.58 (0.27–1.21)
NoUPC
Nakamura, 2017 [22]MelanomaN9/35Vitiligo1–2OS: 0.16 (0.03–0.79)
PFS: 0.58 (0.27–1.21)
NoURC
Grangeon, 2018 [14]NSCLCN/P124/270Global1–4OS: 0.29 (0.18–0.46)
PFS: 0.42 (0.32–0.57)
NoURC
53/270Thyroiditis1–4OS: 0.46 (0.25–0.86)
PFS: 0.58 (0.39–0.85)
11/270Colitis1–4OS: 0.24 (0.03–1.73)
PFS: 0.73 (0.35–1.50)
8/270Hepatitis1–4OS: 0.97 (0.30–3.08)
PFS: 0.94 (0.45–2.08)
6/270Pneumonitis1–4OS: 1.42 (0.45–1.54)
PFS: 1.19 (0.52–2.7)
Toi, 2018 [18]NSCLCN/P66/137Global1–4OS: 0.42 (0.24–0.71)
PFS: 0.45 (0.30–0.68)
NoURC
Sato, 2018 [31]NSCLCN11/18eGlobal1–4PFS: 0.28 (0.04–1.46)60 daysURC
Rogado, 2018 [25]MultipleN/P40/106Global1–4OS: 0.909 (0.625–1.429)f
PFS: 0.435 (0.278–0.714)f
NoMRC
Ricciuti, 2018 [15]NSCLCN85/195Global1–4OS: 0.38 (0.26–0.56)
PFS: 0.48 (0.34–0.67)
NoMRC
39/195Endocrine1–2
OS: 0.59 (0.40–0.89)
PFS: 0.46 (0.24–0.89)
32/195Hepatobiliary1–4OS: 0.94 (0.53–1.66)
PFS: 0.72 (0.41–1.24)
21/195Skin1–4OS: 0.80 (0.46–1.39)
PFS: 0.57 (0.35–0.95)
17/195Gastrointestinal1–4OS: 0.52 (0.30–0.90)
PFS:0.50 (0.26–0.98)
16/195Lung1–4PFS: 0.45 (0.28–0.72)
OS: 0.56 (0.33–0.96)
Ksienski, 2018 [24]NSCLCN/P91/246Global1–2OS: 0.85 (0.50–1.42)6 weeksMRC
25/180≥3OS: 2.29 (1.05–4.98)
Faje, 2018 [8]MelanomaI64/281HypophysitisN.A.OS: 0.53 (0.36–0.75)NoURC
Indini, 2018 [4]MelanomaN/P102/173Global1–5OS: 0.39 (0.18–0.81)
PFS: 0.47 (0.26–0.86)
NoMRC
Lesueur, 2018 [26]NSCLCN62/104Global1–4OS: 0.640 (0.377–1.087)
PFS: 0.660 (0.433–1.099)
NoMRC
Owen, 2018 [5]NSCLCN/P/A27/91Global1–4OS: 0.364 (0.203–0.649)fNoURC
Lisberg, 2018 [27]NSCLCP28/97Global1–4OS: 0.72 (0.49–1.05)
PFS: 0.62 (0.40–0.96)
NoMRC
Fujimoto, 2018 [30]NSCLCN68/613Global≥3PFS: 0.76 (0.55–1.01)NoMRC
62/613Pneumonitis1–4PFS: 0.71 (0.52–0.97)
Okada, 2019 [6]MelanomaN8/15Global1–2OS: 0.01 (0.00011–0.88)NoMRC
Lei, 2019 [16]MultipleN/P34/103Thyroiditis1–4OS: 0.40 (0.19–0.85)
PFS: 0.45 (0.27–0.76)
NoURC
Cortellini, 2019 [19]NSCLCN/P224/524Global1–4OS: 0.55 (0.41–0.72)
PFS: 0.59 (0.47–0.76)
6 weeksMRC
50/5593–4OS: 0.53 (0.41–0.69)
PFS: 0.75 (0.51–1.11)
NoM
78/559Endocrine1–4OS: 0.55 (0.37–0.83)
PFS: 0.63 (0.45–0.89)
NoM
59/559Skin1–4OS: 0.43 (0.27–0.70)
PFS: 0.46 (0.31–0.69)
NoM
51/559Gastrointestinal1–4OS: 0.61 (0.38–0.98)
PFS: 0.68 (0.47–1.01)
NoOS: M
PFS: U
23/559Pneumonitis1–4OS: 1.32 (0.79–2.19)
PFS: 1.20 (0.76–1.92)
NoU
10/559Hepatic1–4OS: 1.09 (0.48–2.45)
PFS: 1.47 (0.72–2.96)
NoU
Ahn, 2019 [21]NSCLCN/POS: 55/133
PFS: 51/111
Global1–4OS: 0.484 (0.255–0.919)
PFS: 0.434 (0.256–0.735)
6 weeksMRC
OS: 26/133
PFS: 24/133
Skin1–2OS: 0.420 (0.162–1.087)
PFS: 0.643 (0.350–1.180)
   
OS: 14/133
PFS: 14/111
Endocrine1–4OS: 0.255 (0.051–1.288)
PFS: 0.368 (0.132–1.028)
   
OS: N.A./133
PFS: N.A./111
Pneumonitis1–4OS: 4.177 (1.420–11.942)
PFS: 1.686 (0.618–4.597)
   
Berner, 2019 [20]NSCLCN/P48/83SkinN.A.OS: 0.29 (0.12–0.71)
PFS: 0.22 (0.09–0.39)
NoUPC
Verzoni, 2019 [7]RCCN77/389Global1–4OS: 0.57 (0.35–0.93)NoMRC
Yamauchi, 2019 [13]MultipleNOS: 67/191
PFS: 61/175
ThyroidN.A.OS: 0.61 (0.39–0.93)
PFS: 0.66 (0.46–0.95)
NoURC
Bjørnhart, 2019 [28]NSCLCN/P25/112Global3–4OS: 0.47 (0.21–1.05)
PFS: 0.71 (0.39–1.27)
NoURC
Ishihara, 2019 [17]RCCN23/47Global1–4PFS: 0.25 (0.11–0.56)NoMRC
Moel, 2019 [33]MelanomaI81/133 eGlobal1–4OS: 1.12 (0.7–1.79)NoURC
Lang, 2019 [29]MelanomaI29/100Diarrhea1–3OS: 1.32 (0.71–2.44)
PFS: 1.40 (0.88–2.22)
NoURC
7/100Diarrhea3OS: 2.15 (0.76–6.07)
PFS: 1.96 (0.89–4.32)
  1. 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
  2. aThe patients group receiving a dose of 10 mg/kg every 3 weeks
  3. bThe patients group receiving a dose of 10 mg/kg every 2 weeks
  4. cThe patients group receiving a dose of 2 mg/kg every 3 weeks
  5. dThe 95% CI was calculated according to the HR and p value
  6. eThe sample size was estimated from the manuscript
  7. fThe HR and 95% CI was calculated through taking reciprocal