Table 2.
Summary of key phase III trials using immune checkpoint inhibitors as first-line monotherapy or combination therapy for NSCLC.
| Study | Cohort size | PD-L1 expression | Treatment arms | NSCLC histological type | Median PFS (months) | Median OS (months) | ORR (%) | OS rate (%) a | Ref |
|---|---|---|---|---|---|---|---|---|---|
| ICI monotherapy | |||||||||
| KEYNOTE-024 | 305 | PD-L1 ≥ 50% | Pembrolizumab vs. platinum-based chemotherapy | NSQ+SQ | 10.3 vs. 6.0 b | 26.3 vs. 13.4 | 44.8 vs. 27.8 | 31.9 vs. 16.3 (5-year rate) | (60, 61) |
| KEYNOTE-042 | 1274 | PD-L1 ≥ 1% | Pembrolizumab vs. platinum-based chemotherapy | NSQ+SQ | 5.4 vs. 6.5 | 16.4 vs. 12.1 b | 27.0 vs. 27.0 | 25 vs. 17 (3-year rate) | (34, 35) |
| PD-L1 ≥ 20% | 6.2 vs. 6.6 | 18.0 vs. 13.0 b | 33 vs. 29 | 28 vs. 19 (3-year rate) | |||||
| PD-L1 ≥ 50% | 7.1 vs. 6.4 | 20.0 vs. 12.2 b | 39 vs. 32 | 31 vs. 18 (3-year rate) | |||||
| KEYNOTE-042 China extension | 262 | PD-L1 ≥ 1% | Pembrolizumab vs. platinum-based chemotherapy | NSQ+SQ | 6.3 vs. 6.7 | 20.2 vs. 13.5 b | 31.3 vs. 24.6 | 43.8 vs. | (36) |
| PD-L1 ≥ 20% | 6.2 vs. 7.2 | 21.9 vs. 13.5 b | 33.7 vs. 24.3 | 28.2 (2-year rate) | |||||
| PD-L1 ≥ 50% | 8.3 vs. 6.5 | 24.5 vs. 13.8 b | 40.3 vs. 24.3 | 46.5 vs. | |||||
| 28.7 (2-year rate) | |||||||||
| 50.0 vs. | |||||||||
| 29.7 (2-year rate) | |||||||||
| IMpower110 | 554 | TC 1/2/3/and IC 1/2/3 (analysis in TC 3/IC 3) | Atezolizumab vs. chemotherapy | NSQ+SQ | 8.1 vs. 5.0 | 20.2 vs. 14.7 b | 38.3 vs. 28.6 | (40, 41) | |
| EMPOWER Lung 1 | 563 | PD-L1 ≥ 50% | Cemiplimab vs. chemotherapy | NSQ+SQ | 8.2 vs. 5.7 b | NR vs. 14.2 b | 39 vs. 20 | (46) | |
| CheckMate 026 | 423 | PD-L1 ≥ 1% (primary endpoint assessed in PD-L1 ≥ 5%) | Nivolumab vs. chemotherapy | NSQ+SQ | 4.2 vs. 5.9 b | 14.4 vs. 13.2 | 26.0 vs. 33.0 | (62) | |
| ICI plus chemotherapy | |||||||||
| KEYNOTE-189 | 616 | PD-L1 unselected | Pembrolizumab/PC vs. PC | NSQ | 9.0 vs. 4.9 b | 22.0 vs. 10.7 b | 48.0 vs. 19.4 | 31.3 vs. 17.4 (3-year rate) | (33) |
| IMpower130 | 723 | PD-L1 unselected | Atezolizumab/chemotherapy vs. chemotherapy | NSQ | 7.0 vs. 5.5 b | 18.6 vs. 13.9 b | 49.2 vs. 31.9 | 39.6 vs. 30.0 (2-year rate) | (44, 45) |
| CameL | 412 | PD-L1 unselected | Camrelizumab/ chemotherapy vs. chemotherapy | NSQ | 11.3 vs. 8.3 b | 27.9 vs. 20.5 | 60.5 vs. 38.6 | (48, 49) | |
| ORIENT-11 | 397 | PD-L1 unselected | Sintilimab/ chemotherapy vs. chemotherapy | NSQ | 8.9 vs. 5.0 b | Not reported | 51.9 vs. 29.8 | (53) | |
| ORIENT-12 | 357 | PD-L1 unselected | Sintilimab/chemotherapy vs. chemotherapy | SQ | 5.5 vs. 4.9 b | Not reached | 44.7 vs. 35.4 | (54) | |
| RATIONALE 304 | 332 | PD-L1 unselected | Tislelizumab/chemotherapy vs. chemotherapy | NSQ | 9.7 vs. 7.6 b | Not reached | 57.4 vs. 36.9 | (52) | |
| KEYNOTE-407 | 559 | PD-L1 unselected | Pembrolizumab/chemotherapy vs. carboplatin/ nab-paclitaxel | SQ | 8.0 vs. 5.1 b | 17.1 vs. 11.6 b | 62.6 vs. 38.4 | 29.7 vs. 18.2 (3-year rate) | (37, 38) |
| KEYNOTE-407 China extension | 125 | PD-L1 unselected | pembrolizumab/chemotherapy vs. carboplatin/ (nab-) paclitaxel | SQ | 8.3 b vs. 4.2 | 17.3 vs. 12.6 b | 78.5 vs. 41.7 | (63) | |
| CameL-sq | 390 | PD-L1 unselected | Camrelizumab/ chemotherapy vs. chemotherapy | SQ | 8.5 vs. 4.9 b | NR vs. 14.5 | 64.8 vs. 36.7 | (64) | |
| RATIONALE 307 | 360 | PD-L1 unselected | Tislelizumab/PC or nab-PC vs. PC | SQ | 7.6, 7.6 vs. 5.5 b | Not reported | 73,75 vs. 50 | (50, 51) | |
| GEMSTONE-302 | 479 | PD-L1 unselected | Sugemalimab/chemotherapy vs. chemotherapy | NSQ+SQ | 7.8 vs. 4.9 b | Not reported | 61.4 vs. 39.2 | (65) | |
| ICI plus chemotherapy and antiangiogenic therapy | |||||||||
| IMpower150 | 1202 | Analysis in PD-L1 unselected, EGFR/ALK | Chemotherapy plus bevacizumab ± atezolizumab | NSQ | 8.3 vs. 6.8 b | 19.5 vs. 14.7 b | 63.5 vs. 48.0 | 43.4 vs. 33.7 (2-year rate) | (42, 43) |
| WT (study included any EGFR/ALK status) | |||||||||
| Dual ICI | |||||||||
| KEYNOTE-598 | 568 | PD-L1 ≥ 50% | Pembrolizumab ± ipilimumab | NSQ+SQ | 8.2 vs. 8.4 b | 21.4 vs. 21.9 b | 45.4 vs. 45.4 | (66) | |
| CheckMate 227 part 1a | 1189 | PD-L1 ≥ 1% | Ipilimumab/ nivolumab vs. chemotherapy | NSQ+SQ | 5.1 vs. 5.6 b | 17.1 vs. 14.9 b | 35.9 vs. 30.0 | 40.0 vs. 32.8 (2-year rate) | (47) |
| Dual ICI plus chemotherapy | |||||||||
| CheckMate 9LA | 719 | PD-L1 unselected | Ipilimumab/ nivolumab/chemotherapy vs. chemotherapy | NSQ+SQ | 6.8 vs. 5.0 | 15.6 vs. 10.9 b | 37.7 vs. 25.1 | (45) | |
IC, tumor-infiltrating immune cells covering % of the tumor area; ICI, immune checkpoint inhibitor; NSQ, nonsquamous cell carcinoma; OS, overall survival; PFS, progression-free survival; PC, carboplatin/pemetrexed; ORR, objective response rate; SQ, squamous cell carcinoma; TC, expression of PD-L1 on tumor cells.
a
Only survival rates ≥ 2 years are shown.
b
Primary endpoint.