非小细胞肺癌：免疫检查点抑制剂：汇总🔢

研究组

对照组

人群

主要终点

ORR

MPFS,月

PFS,HR

mOS,月

OS, HR

mOS,月*

OS,HR(95% CI)*

PFS,HR(95% CI)*

Keynote 024

帕博利珠单抗 forup to 2 years

含铂双药化疗; 非鳞癌+培美曲塞维持治疗

PD-L1 ≥50%

PFS

46%

7·7

0·50

26·3

0·62

NA

NA

NA

Keynote 598

帕博利珠单抗 plus 伊匹木单抗

帕博利珠单抗加安慰剂

PD-L1 ≥50%

OS和 PFS

45%

8·2

1·06

21·4

1·08

NA

NA

NA

Empower-Lung 1

Cemiplimab 直至进展或2年

含铂双药化疗; 非鳞癌+培美曲塞维持治疗

PD-L1 ≥50%

OS和 PFS

39%

8·2

0·54

23·4

0·56

NA

NA

NA

CheckMate 026

纳武利尤单抗至进展或不耐受

含铂双药化疗; 4-6周期，q3w

PD-L1 ≥5%

PFS

26%

4·2

1·15

14·4

1·02

NA

NA

NA

Keynote 042

帕博利珠单抗 for up to 2 years

含铂双药化疗; 非鳞癌+培美曲塞维持治疗

PD-L1 ≥1%

OS

27%

5·5

1·05

16·4

0·8

NA

NA

NA

Impower-110

阿替利珠单抗至进展或不耐受

含铂双药化疗 加支持治疗或者非鳞癌+培美曲塞维持治疗

PD-L1 ≥1%

OS

40%

5·8

0·72

18·9

0·85 (NS)‡

NA

NA

NA

CheckMate 227

纳武利尤单抗 plus 伊匹木单抗 for upto 2 years

含铂双药化疗

Any PD-L1

OS in PD-L1 ≥1%

36%

5·1§

0·79

17·1

0·79¶

17·2

0·62 (0·48–0·78)

0·73 (0·56–0·95)

Keynote 189

帕博利珠单抗 plus platinum plus pemetrexed followed by 帕博利珠单抗 plus pemetrexed; every 3 weeks up to 31 cycles

Placebo plus platinum plus pemetrexed followed by placeboplus pemetrexed, up to 31 cycles

Any PD-L1

OS, PFS

48%

9·0

0·50

22·0

0·60

17·2

0·59 (0·36–0·74)

0·75 (0·53–1·05)

IMpower-132

Atezolizumab plus platinum plus pemetrexed followed by atezolizumab plus pemetrexed, untilPD or toxicity

Platinum plus pemetrexed followed by pemetrexed; every3 weeks until progressive disease or toxicity

Any PDL-L1

OS和 PFS

47%

7·6

0·60

17·5

0·86 (NS)

15·9

0·67 (0·46–0·96)

0·45 (0·31–0·64)

IMpower-150

Atezolizumab, bevacizumab, carboplatin, and paclitaxel, followed by atezolizumab plus bevacizumab until progressive diseaseor toxicity

Bevacizumab, carboplatin, and paclitaxel, followed by bevacizumab until progressive diseaseor toxicity

Any PD-L1‖

OS和 PFS

64%

8·4

0·57

19·5

0·8

16·9

0·90 (0·71–1·14)

0·77 (0·61–0·99)

IMpower-130

Atezolizumab plus carboplatin plus nab-paclitaxel followed by atezolizumab until progressive diseaseor toxicity

Carboplatin plus nab-paclitaxel followed by or pemetrexed until progressive diseaseor toxicity

Any PD-L1

OS和 PFS

49%

7·0

0·64

18·6

0·79

12·0

0·79 (0·64–0·98)

0·72 (0·56–0·91)

CheckMate 9LA

纳武利尤单抗 plus 伊匹木单抗with 2 cycles of platinum doublet chemotherapy followed by 纳武利尤单抗 plus 伊匹木单抗

含铂双药化疗

Any PD-L1

OS

38%

6·7

0·68**

14·1

0·69**

NR

0·62 (0·45–0·85)

0·71 (0·53–0·94)

POSEIDON

度伐利尤单抗加化疗后度伐利尤单抗维持

含铂方案化疗

Any PD-L1

OS

48%

5·5

0·74

13·3

0·86 (NS)

NR

0·97 (0·73–1·28)

NR

POSEIDON

Tremelimumab +度伐利尤单抗 plus 化疗，度伐利尤单抗维持至进展, 在第16周加一剂tremelimumab

含铂方案化疗

Any PD-L1

PFS

46%

6·2

0·72

14

0·77

NR

0·78 (0·59–1·03)

NR

Empower-Lung 3

Cemiplimab plus 含铂双药化疗 followed by cemiplimab for up to 2years

含铂方案化疗

Any PD-L1

OS

43%

8·2

0·56

21·9

0·71

NR

1·01 (0·63–1·60)

0·76 (0·51–1·15)

MYSTIC

Durvalumab

含铂方案化疗

Any PD-L1††

OS in PD-L1 ≥25%

36%

4·7

0·87 (NS)

16·3

0·76 (NS)

NA

NA

NA

MYSTIC

Durvalumab plus tremelimumab

含铂方案化疗

Any PD-L1††

OS和 PFS in PD-L1 ≥25%

34%

3·9

1·05

11·9

0·85 (NS)

NA

NA

NA

ORIENT-11

Sintilimab plus platinum plus pemetrexed followed by sintilimab plus pemetrexed for up to 2 years

Placebo plus platinum plus pemetrexed followed by placeboplus pemetrexed for up to2 years

Any PD-L1

PFS

52%

8·9

0·48

24·2

0·65

NR

0·75 (0·48–1·19)

0·66 (0·41–1·09)

RATIONALE-304

Tislelizumab plus platinum plus pemetrexed, followed by tislelizumab plus pemetrexed until progressive diseaseor toxicity

Platinum plus pemetrexed followed by pemetrexed until progressive diseaseor toxicity

Any PD-L1

PFS

52%

9·8

0·61

NR

NR

NR

NR

0·76 (0·47–1·22)

Camel

Camrelizumab plus carboplatin plus pemetrexed followed by camrelizumab plus pemetrexed until progressive diseaseor toxicity for up to 2 yearsfor camrelizumab

Carboplatin plus pemetrexed followed by pemetrexed until progressive disease or toxicity

Any PD-L1

PFS

61%

11·3

0·60

27·1

0·72

19

0·84 (0·55–1·27)

0·75 (0·5–1·13)

Keynote 407

帕博利珠单抗 plus carboplatin plus nab-paclitaxel followed by 帕博利珠单抗 up to 31 cycles

Placebo plus carboplatin plus nab-paclitaxel followed by placebo up to 31 cycles

Squamous, any PD-L1

OS和 PFS

63%

8·0

0·59

17·2

0·71

15

0·83 (0·61–1·13)

0·70 (0·52–0·95)

Impower-131

Atezolizumab, carboplatin, or nab-paclitaxel followed by atezolizumab until progressive diseaseor toxicity

Carboplatin and nab-paclitaxel

Squamous, any PD-L1

OS和 PFS

49%

6·3

0·71

14·2

0·88 (NS)

14

0·87 (0·67–1·13)

0·82 (0·65–1·04)

Camel-Sq

Camrelizumab, carboplatin, or paclitaxel followed by camrelizumab until progressive diseaseor toxicity

Placebo plus carboplatin plus paclitaxel followed by placebo untilprogressive diseaseor toxicity

Squamous, any PD-L1

PFS

65%

8·5

0·37

27·4

0·57

NR

NR

NR

RATIONALE-307

Tislelizumab plus carboplatin plus paclitaxel followed by tislelizumab until progressive diseaseor toxicity

Carboplatin plus paclitaxel

Squamous, any PD-L1

PFS

73%

7·6

0·52

NR

NR

NR

NR

0·64 (0·37–1·10)

ORIENT-12

Sintilimab plus platinum plus gemcitabine followed by sintilimab for upto 2 years

Placebo plus platinumplus gemcitabine followed by placebo for up to 2 years

Squamous, any PD-L1

PFS

45%

5·5

0·54

NR

0·57

NR

0·55 (0·37–0·81)

NR

GEMSTONE-302

Sugemalimab plus carboplatine and paclitaxel (squamous) or pemetrexed (non-squamous) followed by sugemalimab (plus pemetrexed for non-squamous)

Placebo plus carboplatine and paclitaxel (squamous) or pemetrexed (non-squamous) followed by placebo (pluspemetrexed for non-squamous)

Squamous or non-squamous, any PD-L1

PFS

61%

9·0

0·48

NR

NR

NR

NR

0·56 (0·40–0·77)

ORIENT-31

Sintilimab, IBI305 (biosimilar anti-VEGF), pemetrexed and cisplatin, followed by sintilimab, IBI305, and pemetrexedfor up to 2 years

Pemetrexed and cisplatin, followed by pemetrexed

EGFR mutation, progressed after 研究组 with EGFR TKI

PFS

44%

7·2

0·51

21·1

0·98 (NS)

NR

NR

NR

CheckMate 722

纳武利尤单抗 plus platinum and pemetrexed followed by 纳武利尤单抗 (for upto 2 years) plus pemetrexed

Platinum and pemetrexed followed by pemetrexed

EGFR, progressed after 研究组 with EGFR TKI and no exon 20 Thr790Met mutation

PFS

31%

5·6

0·75 (NS)

19·4

0·82 (NS)

NR

NR

0·91

IPSOS

Atezolizumab until progression

Vinorelbine or gemcitabine

Unsuitable for platinum-based chemotherapy

OS

17%

4·2

0·87 (NS)

10·3

0·78

NR

NR

NR

For full references see appendix. HR=hazard ratio. NR=Not reported. NS=not statistically significant. TKI=tyrosine kinase inhibitor. *PD-L1 <1%. †Negative trial. ‡Positive and statistically significant for PD-L1 ≥50%. §For PD-L1 ≥1%. ¶HR (97·72% CI) for overall survival in those who were PD-L1 negative; crossing of the curves for progression-free survival. ‖EGFR and ALK authorised. **HR (97·72% CI). ††488 patients with PD-L1 ≥25% were included in the analysis.
Table 2: Main trials and approval for immune checkpoint inhibitors for patients with advanced NSCLC
Meyer ML, Fitzgerald BG, Paz-Ares L, Cappuzzo F, Jänne PA, Peters S, Hirsch FR. New promises and challenges in the treatment of advanced non-small-cell lung cancer. Lancet. 2024 Aug 24;404(10454):803-822. doi: 10.1016/S0140-6736(24)01029-8. Epub 2024 Aug 6. PMID: 39121882.