Table1 Basic characteristics of enrolled studies

AVAiL

2009

III

Double-blinded

IIIB/IV,recurrent

NSCLC

Bevacizumab_Cisplatin_

Gemcitabine

Placebo_Cisplatin_Gemcitabine

BEYOND2016

2015

III

Double-blinded

IIIB/IV,recurrent

Non-squa NSCLC

Bevacizumab _Carboplatin_Paclitaxel

Placebo_Carboplatin_Paclitaxel

BR24

2010

II

Double-blinded

IIIB/IV

NSCLC

Cediranib_ Carboplatin_

Paclitaxel

Placebo_ Carboplatin_Paclitaxel

BR29

2014

III

Double-blinded

IIIB/IV

NSCLC

Cediranib_ Carboplatin_

Paclitaxel

Placebo_ Carboplatin_Paclitaxel

CameL

2020

III

Open-label

IIIB/IV

Non-squa NSCLC

Camrelizumab_Carboplatin_ Pemetrexed

Carboplatin_Pemetrexed

CameL-sq

2021

III

Double blind

IIIB/IV

Squa NSCLC

Camrelizumab _Carboplatin_ Paclitaxel

Placebo _Carboplatin_Paclitaxel

Chandra P Belani2014

2014

II

Open-lable

IIIB/IV,recurrent

Non-squa NSCLC

Axitinib_

Cisplatin_

Pemetrexed

Cisplatin_Pemetrexed

CheckMate 026

2017

III

open-label

IV,recurrent

NSCLC

Nivolumab

Chemotherapy

CheckMate 227

2019

III

open-label

IV

NSCLC

Nivolumab _Ipilimumab

Chemotherapy

CheckMate 9LA

2021

III

open-label

IV,recurrent

NSCLC

Nivolumab_ Ipilimumab_ Chemotherapy

chemotherapy

David H. Johnson 2004

2004

II

Open-lable

IIIB/IV,recurrent

NSCLC

Bevacizumab_Carboplatin_

Paclitaxel

Carboplatin _Paclitaxel

DENG Tao2014

2014

-

-

III/IV

NSCLC

Bevacizumab _ Cisplatin_

Pemetrexed

Cisplatin_Pemetrexed

E4599

2006

III

—

IIIB/IV,recurrent

NSCLC

Bevacizumab_Carboplatin_Paclitaxel

Carboplatin_Paclitaxel

Empower-lung1

2020

III

Open-lable

III/IV

NSCLC

Cemiplimab

Chemotherapy

ERACLE

2015

III

Not-mentioned

IIIB/IV

Non-squas NSCLC

Bevacizumab_Carboplatin_Paclitaxel

Cisplatin_Pemetrexed

ESCAPE

2010

III

-

IIIB/IV

NSCLC

Sorafenib _Carboplatin_Paclitaxel

Placebo _Carboplatin_Paclitaxel

GEMSTONE-302

2020

III

Double-blinded

IV

NSCLC

Sugemalimab _Chemotherapy

Carboplain_Paclitiaxel–SQ;Carbooplatin_Pemetrexed—NSQ

Govindan2017

2017

III

Double blind

IV,recurrent

Squa NSCLC

Ipilimumab _Carboplatin_Paclitaxel

Placebo_Carboplatin_Paclitaxel

HANB2011

2011

Double-blinded

IIIB ~ IV

NSCLC

Endostar_Carboplatin_Paclitaxel

Carboplatin_Paclitaxel

HANL2009

2009

Endostar TXT_DDP

TXT_DDP

Impower110

2020

III

open-label

IV

NSCLC

Atezolizumab

Chemotherapy

IMpower130

2019

III

open-label

IV

Non-squa NSCLC

Atezolizumab_Carboplatin_ Nab-paclitaxel

Carboplatin_ Nab-paclitaxel

IMpower131

2020

III

open-label

IV

Squa NSCLC

Atezolizumab _Carboplatin_ Paclitaxel/Nab-paclitaxel

Carboplatin_Nab-paclitaxel

IMpower132

2020

III

open-label

IV

Non-squa NSCLC

Atezolizumab _Cisplatin/ Carboplatin_ Pemetrexed

Cisplatin/Carboplatin_Pemetrexed

IMpower150

2018

III

open-label

IV,recurrent

Non-squa NSCLC

Atezolizumab_Carboplatin_Paclitaxel;

Atezolizumab_Bevacizumab_Carboplatin

_ Paclitaxel

Bevacizumab_Carboplatin_Paclitaxel

JO19907

2012

II

Open-lable

IIIB/IV,recurrent

Non-squa NSCLC

Bevacizumab_Carboplatin_Paclitaxel

Carboplatin_Paclitaxel

JSLCG-001

2019

III

Open-lable

IIIB/IV

Squa NSCLC

Endostar_Cisplatin_Docetaxel

Cisplatin_Docetaxel

KEYNOTE-021G

2020

II

open-label

IIIB to IV

Non-squa NSCLC

Pembrolizumab_Carboplatin_Pemetrexed

Carboplatin_Pemetrexed

KEYNOTE-024

2016

III

open-label

IV

NSCLC

Pembrolizumab

Chemotherapy

KEYNOTE-042

2018

III

open-label

III/IV

NSCLC

Pembrolizumab

Carboplatin_ paclitaxel/pemetrexed

KEYNOTE-042China

2020

III

open-label

III/IV

NSCLC

Pembrolizumab

Carboplatin_ paclitaxel/pemetrexed

KEYNOTE-189

2018

III

Double blind

IV

Non-squaNSCLC

Pembrolizumab_Carboplatin/Cisplatin_Pemetrexed

Placebo_Carboplatin/Cisplatin _Pemetrexed

KEYNOTE-407

2020

III

Double blind

IV

Squa NSCLC

Pembrolizumab_Carboplatin_Paclitaxel/Nab-paclitaxel

Placebo_Carboplatin_Paclitaxel /Nab-paclitaxel

Keynote-407 China Extension

2019

III

Double blind

IV

Squa NSCLC

Pembrolizumab_Carboplatin_Paclitaxel /Nab-paclitaxel

Placebo _ Carboplatin_Paclitaxel /Nab-paclitaxel

Keynote-598

2021

III

Double-blinded

IV

NSCLC

Pembrolizumab_Ipilimumab

Pembrolizumab

LOGIK1201

2019

II

IIIB/IV,recurrent

Non-squamous NSCLC

Bevacizumab_Pemetrexed

Pemetrexed

Luis G2012

2012

III

Double-blinded

IIIB-IV

Non-squamous NSCLC

Sorafenib_Cisplatin_Gemcitabine

Placebo_Cisplatin_Gemcitabine

Lynch2012

2012

II

Double blind

IIIB to IV

NSCLC

Ipilimumab_Carboplatin_Paclitaxel

Placebo _Carboplatin_Paclitaxel

MONET1-NSQ

2012

III

Double-blinded

IIIB/IV

Non-squaNSCLC

Motesanib_Carboplatin_Paclitaxel

Carboplatin_Paclitaxel

MONET1-SQ

2014

III

Double-blinded

IIIB/IV,recurrent

Squa NSCLC

Motesanib_Carboplatin_Paclitaxel

Carboplatin_Paclitaxel

MONET-A

2017

III

Double-blinded

IV,recurrent

Non-squamous NSCLC

Motesanib_Carboplatin_Paclitaxel

Placebo_Carboplatin_Paclitaxel

Murakami2010

2010

II

Open-lable

advanced,recurrent

Non-squaNSCLC

Bevacizumab_Cisplatin_Pemetrexed

Cisplatin_Pemetrexed

MYSTIC

2020

III

Open label

IV

NSCLC

Durvalumab;Durvalumab_Tremelimumab

Chemotherapy

ONO-4538–52/TASUKI-52

2020

III

Double-blind

IIIB/ IV

Non-squaNSCLC

Nivolumab_Bevacizumab_ Carboplatin _Paclitaxel

Placebo_Bevacizumab_Carboplatin _Paclitaxel

ORIENT-11

2020

III

Double-blind

IIIB/IV

Non-squamous NSCLC

Sintilimab_Platinum_Pemetrexed

Placebo_Platinum_Pemetrexed

ORIENT-12

2020

III

Double-blind

IIIB to IV

Squa NSCLC

Sintilimab_Cisplatin/Carboplatin_Gemcitabine

Placebo_Cisplatin/Carboplatin_Gemcitabine

Prounce

2015

III

Open-label

IV

Non-squaNSCLC

Bevacizumab_Carboplatin_Paclitaxel

Carboplatin_Paclitaxel

Qun Chen2017

2017

—

—

—

NSCLC

Endostar_Gemcitabine

Gemcitabine

RATIONALE304

2020

III

Open-label

IIIB to IV

Non-squaNSCLC

Tislelizumab _Carboplatin/Cisplatin_Pemetrexed

Carboplatin/Cisplatin_ Pemetrexed

RATIONALE307

2020

III

Open-label

IIIB to IV

Squa NSCLC

Tislelizumab_Carboplatin_Paclitaxel/Nab-paclitaxel

Carboplatin_Paclitaxel

Robert C. Doebele2015

2015

II

Open-label

IV

Non-squaNSCLC

Ramucirumab_Carboplatin /Cisplatin_Pemetrexed

Carboplatin/Cisplatin_ Pemetrexed

S. Thomas2018

2018

II

Open-label

IV

Squa NSCLC

Ramucirumab_Carboplatin /Cisplatin_Gemcitabine

Carboplatin/Cisplatin_Gemcitabine

Siow Ming Lee2009

2009

III

Double-blinded

IIIB/IV

NSCLC

Thalidomide_Carboplatin_Gemcitabine

Placebo_Carboplatin_Gemcitabine

Wang2006

2006

III

Double-blinded

IIIA/IIB/IV

NSCLC

Endostar_Cisplatin_Vinorelbine

Placebo_Cisplatin_Vinorelbine

Xin Zhao 2012

2012

II

Open-label

IIIB/IV

NSCLC

Endostar_Cisplatin_Gemcitabine

Cisplatin_Gemcitabine

AVAiL

345VS.351VS.347

65%VS.62%VS.64%

57(26–81)VS.59(20–83)VS.59(29–83)

—

38%VS.41%VS.41%

—

No

BEYOND2016

138VS.138

54%VS.56%

57(30–75)VS.56(23–74)

50%VS.44%

25%VS.20%

0%vs.0%

Unclear

BR24

126VS.125

58%VS.59%

60(36–77)VS.58(39–81)

—

21%VS.29%

4%VS.4%

Unclear

BR29

153VS.153

55% VS. 54%

63(23–85) VS. 62(32–77)

86%VS. 84%

25%VS. 28%

—

Unclear

CameL

205VS 207

71% VS. 72%

59 (54–64) VS. 61 (53–65)

62%VS. 63%

23% vs. 17%

5% VS. 2%

Yes

CameL-sq

193VS 196

92.7%VS.91.8%

64(34–74) VS. 62(34–74)

83.9%VS.80.1%

19.7%VS.21.9%

Not mention

Yes

Chandra P Belani2014

55VS.58VS.57

62%VS64%VS65%

62 (30–77)VS. 62 (35–83)VS. 59 (42–76)

73%VS.84%VS.79%

45%VS.43%VS.47%

Not-mentioned

No

CheckMate 026

271VS.270

68% VS. 55%

63(32–89)VS.65(29–87)

88%VS. 87%

31% VS. 34%

12% VS. 13%

Yes

CheckMate 227

583VS.583

67.4% VS. 66.0%

64 (26–87)VS. 64 (29–87)

85.2%VS.85.6%

35% VS. 32.8%

-

No

CheckMate 9LA

361VS 358

70% VS. 70%

65(59–70) VS. 65(58–70)

87%VS. 86%

31%vs.31%

18% VS. 16%

No

David H. Johnson2004

32VS.35 VS.32

62.5% VS. 45.7% VS.75%

46.9% VS. 50.0% VS.54.3%

Unclear

DENG Tao2014

120VS. 120

82% VS. 84%

59.3 ± 7.3 VS. 58.8 ± 6.9

Not-mentioned

Not-mentioned

Not-mentioned

Unclear

E4599

417VS.433

50% VS. 58%

 ≥ 65y(42% VS. 44%)

Not-mentioned

40% VS. 40%

Not-mentioned

Unclear

Empower-lung1

356VS.354

87.6%VS.83.1%

63.0(31.0–79.0)VS.64.0(40.0–84.0)

Not-mentioned

27%VS.27.1%

12.4%VS.11.0%

Yes

ERACLE

58vs.60

70%VS.78%

60 (35–72)VS 62 (41–71)

70%VS.60%

78%VS.79%

Not-mentioned

Unclear

ESCAPE

464VS.462

63% VS. 62%

62(34–86) VS. 63(34–82)

84%VS. 86%

41% VS. 41%

OVS.0

Unclear

GEMSTONE-302

320VS.159

79.4% VS. 81.1%

62.0(29–75) VS.64.0(36–75)

72.5%VS.74.8%

18.4% VS. 15.7%

15.6% VS. 10.7%

Unclear

Govindan2017

388VS.361

84% VS 85%

64(28–84) VS.64(28–85)

87%VS. 88%

35%vs.34%

0 VS 0

Unclear

HANB2011

63VS.63

—

—

—

—

—

Unclear

HANL2009

37VS.31

—

—

—

—

–

Unclear

Impower110

277VS. 277

70.8% VS. 69.7%

64(30–81)VS. 65 (30–87)

86.6%VS.87.3%

35.0%VS.36.8%

No mention

No

IMpower130

483VS. 240

57% VS 58%

64 (18–86)VS. 65 (38–85)

87% VS 92%

42%VS.39%

No mention

Yes

IMpower131

338VS. 343VS .340

82.2% VS 81.6% VS 81.5%

66 (43–85)VS. 65 (23–83)VS. 65 (38–86)

91.1% VS 90.7%VS.92.9%

32.2%vs.33.5%VS.32.4%

No mention

No

IMpower132

292VS. 286

65.8% VS 67.1%

64.0 (31–85)VS. 63.0 (33–83)

87.3% VS 89.5%

43.2%vs.40.1%

No mention

No

IMpower150

400VS.400VS.402

60%VS.59.8%

63 (31 − 89)VS. 63 (31 − 90)

79.5%VS.80.8%

40.1%VS.45.1%

No-mention

No

JO19907

121 VS. 59

64% VS.64%

61 (34–74)VS. 60 (38–73)

69% VS.68%

51% VS. 49%

0VS.0

Unclear

JSLCG-001

94 VS. 94

—

—

—

—

—

Unclear

KEYNOTE-021G

60 VS 63

37% VS. 41%

62.5(40–77)VS.66.0(37–80)

75% VS. 86%

40%VS.46%

20% VS. 11%

Yes

KEYNOTE-024

154VS. 151

59.7% VS 62.9%

64.5 (33–90)VS. 66.0 (38–85)

96.8% VS. 87.4%

35.1%vs.35.1%

11.7% VS.6.6%

Unclear

KEYNOTE-042

637VS.637

71%VS.71%

63.0 (57.0–69.0) VS.63.0 (57.0–69.0)

78%VS.78%

31%VS.30%

5%VS.5%

No

KEYNOTE-042China

—

—

—

—

—

—

No

KEYNOTE-189

410VS.206

62.0% VS. 52.9%

65.0 (34.0–84.0)VS. 63.5 (34.0–84.0)

88.3% VS. 87.9%

45.4% VS. 38.8%

17.8% VS. 17.0%

Yes

KEYNOTE-407

278VS.281

79.1% VS. 83.6%

65.0 (29‒87)VS. 65.0 (36‒88)

92.1% VS.93.2%

26.3%VS.32.0%

7.2% VS. 8.2%

Yes

Keynote-407 China Extension

65vs.60

—

—

—

—

—

—

Keynote-598

284VS.284

71.1%VS.67.3%

64 (35–85)VS.65 (35–85)

89.8%VS.91.2%

35.6%VS.36.6%

10.9%VS.10.2%

Unclear

LOGIK1201

20 VS. 20

60% VS.55%

77.5(75–82)VS.78.5(75–83)

60% VS. 50%

25% VS. 30%

Not-mentioned

Unclear

Luis G2012

385VS.387

59.2% VS. 63.3%

59(28–81) VS. 58(22–77)

72.6% VS. 74.7%

37.9% VS. 37.0%

0VS.0

Unclear

Lynch2012

70vs.68vs.66

76% VS. 72% VS. 74%

59(36–82) VS. 61(36–88) VS. 62(36–82)

Not-mention

27% VS 37% VS 23%

Not mention

Unclear

MONET1-NSQ

541VS.549

62% VS. 61%

60.0 (23–87)VS. 60.0 (21–84)

72% VS. 72%

35% VS.38%

Not-mentioned

Unclear

MONET1-SQ

182VS.178

80% VS. 84%

62.0 (31─79)VS. 59.5 (32─81)

84% VS. 89%

35% VS. 37%

5% VS. 5%

Unclear

MONET-A

197VS.204

71.6% VS. 72.1%

65 (59, 70)VS. 64 (58, 69)

75.1% VS. 68.6%

47.2% VS. 43.6%

Not-mentioned

Unclear

Murakami2010

121.VS. 59

64% VS.64%

61 VS. 60

Not-mentioned

51% vs. 49%

0VS.0

Unclear

MYSTIC

163VS. 163VS.162

69.3%VS.72.4% VS.65.4%

64.0 (32–84)VS. 65.0 (34–87) VS64.5 (35–85)

85.3% VS.84.7% VS.87%

35.0% VS.39.9% VS. 43.2%

Not-mentioned

Unclear

ONO-4538–52/TASUKI-52

237VS.275

—

—

—

—

—

Unclear

ORIENT-11

266VS.131

76.7% VS. 75.6%

61 (30, 75)VS 61 (35, 75)

64.3% VS. 66.4%

28.6% VS. 26.0%

Not mention

Yes

ORIENT-12

179VS.178

91.1% VS. 92.1%

64 (39–75)VS. 62 (33–75)

86.6% VS. 82.6%

16.8% VS. 12.4%

Not mention

Yes

Prounce

179VS.182

58.1% VS. 57.7%

65.4 (41.2–86.2)VS.65.8 (38.4–84.1)

90.1% VS. 96.1%

46.7% VS. 46.9%

12.6% VS.17.9%

Unclear

Qun Chen2017

62 VS. 56

—

—

—

—

––

Unclear

RATIONALE304

223VS 111

75.3% VS 71.2%

60(27,75) VS. 61(25,74)

65.9% VS. 59.5%

24.2% VS 21.6%

4.9% VS. 6.3%

Yes

RATIONALE307

120VS.119 VS 121

89.2%VS94.1% VS 91.7%

60 (41–74)VS. 63 (38–74)VS. 62 (34–74)

80.0% VS 89.9% VS 81.0%

25.8% VS. 18.5% VS 26.4%

1.7% VS. 2.5% VS. 0.8%

Yes

Robert C. Doebele2015

69 VS.71

52.2% VS. 63.4%

 ≥ 65y(46.4% VS. 47.9%)

22.5% VS. 15.9%

-

Not-mentioned

Unclear

S. Thomas2018

71 VS. 69

—

—

—

—

—

Unclear

Siow Ming Lee2009

372VS.350

65% VS. 64%

63(35–84) VS. 62(33–84)

Not-mentioned

30% VS. 31%

Not-mentioned

Unclear

Wang2006

230VS.117

—

—

—

—

—

Unclear

Xin Zhao2012

33 VS. 36

63.64%VS.69.44%

61(37–73)VS. 60 (35–72)

Not-mentioned

12.12% VS. 13.89%

Not-mentioned

No