Table 1.
Clinical characteristics of included trials.
| Trial/Year | Phase | Treatment line | Primary endpoint | Median follow-up (months) | Treatment | Size (with/without BMs) | ICIs class | With BMs | Without BMs | ||
|---|---|---|---|---|---|---|---|---|---|---|---|
| OS | PFS | OS | PFS | ||||||||
| HR (95% CI) | HR (95% CI) | HR (95% CI) | HR (95% CI) | ||||||||
| Keynote-010/2016 (3) | 3 | ≥2 | OS, PFS | 13·1 | Pembrolizumab | 104/586 | Anti-PD-1 | 0.83 (0.62–1.10) | 0.96 (0.73–1.25) | 0.78 (0.71–0.85) | 0.91 (0.84–0.99) |
| Doctaxel | 48/295 | ||||||||||
| Keynote-024/2016 (4) | 3 | 1 | PFS | 11.2 | Pembrolizumab | 18/136 | Anti-PD-1 | 0.83 (0.62–1.10) | 0.96 (0.73–1.25) | 0.78 (0.71–0.85) | 0.91 (0.84–0.99) |
| PP/GP/PC | 10/141 | ||||||||||
| Keynote-042/2019 (5) | 3 | 1 | OS | 12.8 | Pembrolizumab | 35/602 | Anti-PD-1 | 0.83 (0.62–1.10) | 0.96 (0.73–1.25) | 0.78 (0.71–0.85) | 0.91 (0.84–0.99) |
| PC/PP | 35/602 | ||||||||||
| Keynote-021/2016 (6) | 2 | 1 | ORR | 10.6 | Pembrolizumab+PP | 9/51 | Anti-PD-1 | 0.48 (0.32–0.70) | 0.44 (0.31–0.62) | 0.63 (0.53–0.75) | 0.55 (0.48–0.63) |
| PP | 6/57 | ||||||||||
| Keynote-189/2018 (7) | 3 | 1 | OS, PFS | 10.5 | Pembrolizumab+PP | 73/337 | Anti-PD-1 | 0.48 (0.32–0.70) | 0.44 (0.31–0.62) | 0.63 (0.53–0.75) | 0.55 (0.48–0.63) |
| PP | 35/171 | ||||||||||
| Keynote-407/2018 (8) | 3 | 1 | OS, PFS | 7.8 | Pembrolizumab+PC/CnP | 20/258 | Anti-PD-1 | 0.48 (0.32–0.70) | 0.44 (0.31–0.62) | 0.63 (0.53–0.75) | 0.55 (0.48–0.63) |
| PC/CnP | 24/257 | ||||||||||
| CheckMate-057/2015 (9) | 3 | ≥2 | OS | 13.2 | Nivolumab | 34/258 | Anti-PD-1 | 1.04 (0.62–1.76) | 0.80 (0.47–1.36) | 0.71 (0.58–0.88) | 0.92 (0.76–1.12) |
| Doctaxel | 34/256 | ||||||||||
| CheckMate-078/2019 (10) | 3 | ≥2 | OS | 8.8 | Nivolumab | 45/293 | Anti-PD-1 | 0.82 (0.42–1.60) | 0.62 (0.35–1.10) | 0.70 (0.53–0.92) | 0.79 (0.62–1.00) |
| Doctaxel | 27/139 | ||||||||||
| CheckMate-227/2019 (11, 12) | 3 | 1 | OS | 28.3 | Nivolumab+Ipilimumab | 64/519 | Anti-PD-1+Anti-CTLA-4 | 0.64 (0.42–0.98) | NR | 0.75 (0.64–0.88) | NR |
| Platinum-based | 52/532 | ||||||||||
| CheckMate-9LA/2020 (13) | 3 | 1 | OS | 8·1 | Nivolumab+Ipilimumab+CT | 65/296 | Anti-PD-1+Anti-CTLA-4 | 0.38 (0.24–0.61) | NR | 0.75 (0.61–0.92) | NR |
| CT | 57/301 | ||||||||||
| OAK/2019 (14, 15) | 3 | ≥2 | OS | 21 | Atezolizumab | 61/364 | Anti-PD-L1 | 0.74 (0.49–1.13) | 0.38 (0.16–0.91) | 0.74(0.63-0.88) | 0.99 (0.50–1.97) |
| Doc | 62/363 | ||||||||||
| SHR-1210-303/2019 (16) | 3 | 1 | PFS | 11.9 | Camrelizumab+PC | 10/194 | Anti-PD-1 | NR | 0.14 (0.01–0.88) | NR | 0.61 (0.46–0.81) |
| PC | 6/201 | ||||||||||
| ORIENT-11/2020 (17) | 3 | 1 | PFS | 8.9 | Sintilimab+PP | 36/230 | Anti-PD-1 | NR | 0.58 (0.28–1.18) | NR | 0.47 (0.34–0.64) |
| PP | 22/109 | ||||||||||
| EMPOWER-Lung1/2020 (18) | 3 | 1 | PFS、OS | 10.8 | Cemiplimab | 44/312 | Anti-PD-1 | 0.44 (0.19–1.07) | 0.49 (0.27–0.90) | 0.71(0.54-0.92) | 0.62 (0.51–0.76) |
| CT | 39/315 | ||||||||||
| Lee/2020 (19) | 3 | 1 | PFS | 7.4 | Nivolumab+PC+Bev | 36/239 | Anti-PD-1 | NR | 0.65 (0.36–1.18) | NR | NR |
| PC+Bev | 41/234 | ||||||||||
OS, overall survival; PFS, progression-free survival; ORR, objective response rate; HR, hazard ratio; 95%CI, confidence interval; ICIs, immune checkpoint inhibitors; BMs, brain metastases; CT, chemotherapy; PP, pemetrexed-cisplatin/carboplatin; PC, paclitaxel-carboplatin; CnP, paclitaxel-nanoparticle albumin-bound-carboplatin; GP, gemcitabine-cisplatin; Bev, bevacizumab; NR, not reported.