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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

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)

  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
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