Table 2.
Efficacy of anti-PD-1/PD-L1 agents for advanced NSCLC in first line.
| Study | Histology | Phase | PD-L1 TPS (%) | Arms | Case number | ORR% (95% CI or p value) | mPFS (95% CI or p value, months) | mOS (95% CI or p value, months) | Grade 3–5 AE% | References |
|---|---|---|---|---|---|---|---|---|---|---|
| KEYNOTE-001 | Squamous or non- squamous | Ib | ⩾50 | Pembrolizumab | 27 | 51.9 (31.9–71.3) | 12.5 (6.2–NR) | NR (22.1–NR) | 11.9 | Hui et al.40 |
| 1–49 | 52 | 17.3 (8.2–30.3) | 4.2 (3.1–6.4) | 19.5 (10.7–22.2) | ||||||
| <1 | 12 | 8.3 (0.2–38.5) | 3.5 (2.1–19.0) | 14.7 (3.4–NR) | ||||||
| KEYNOTE-189 | Non- squamous | III | Any | Pembrolizumab plus chemotherapy | 410 | 47.6 (42.6–52.5) | 8.8 (7.6–9.2) | NR | 67.2 | Gandhi et al.42 |
| Chemotherapy | 206 | 18.9 (13.8–25.0) p < 0.001 | 4.9 (4.7–5.5) p < 0.001 | 11.3 (8.7–15.1) | 65.8 | |||||
| KEYNOTE-189 | Non- squamous | III | Any | Pembrolizumab plus chemotherapy | 410 | 48.0 (43.1–53.0) | 9.0 (8.1–9.9) | 22.0 (19.5–25.2) | 71.9 | Gadgeel et al.43 |
| Chemotherapy | 206 | 19.4 (14.2–22.0) | 4.9 (4.7–5.5) HR: 0.48; (0.40–0.58) | 10.7 (8.7–13.6) HR: 0.56; (0.45–0.70) | 66.8 | |||||
| KEYNOTE-407 | Squamous | III | Any | Pembrolizumab plus chemotherapy | 278 | 57.9 (51.9–63.8) | 6.4 (6.2–8.3) | 15.9 (13.2–NR) | 69.8 | Paz-Ares et al.44 |
| Chemotherapy | 281 | 38.4 (32.7–44.4) | 4.8 (4.3–5.7) p < 0.001 | 11.3 (9.5–14.8) p < 0.001 | 68.2 | |||||
| KEYNOTE-407 | Squamous | III | Any | Pembrolizumab plus chemotherapy | 278 | 62.6 (56.6–68.3) | 8.0 (6.3–8.4) | 17.1 (14.4–19.9) | 74.1 | Paz-Ares et al.45 |
| Chemotherapy | 281 | 38.4 (32.7–44.4) | 5.1 (4.3–6.0) HR: 0.57; (0.47–0.69) | 11.6 (10.1–13.7) HR: 0.71; (0.58–0.88) | 69.6 | |||||
| KEYNOTE-021 | Squamous or non- squamous | I/II | Any | Pembrolizumab plus carboplatin plus paclitaxel | 25 | 48 | 10.3 (6.1–14.6) | 21.4 (10.5–NR) | 40 | Gadgeel et al.46 |
| Carboplatin plus paclitaxel plus bevacizumab | 25 | 56 | 7.1 (4.2–14.3) | 16.7 (8.5–NR) | 42 | |||||
| Carboplatin plus pemetrexed | 24 | 75 | 10.2 (6.5–13.9) | 16.7 (13.9–29.2) | 46 | |||||
| KEYNOTE-021 | Non-squamous | II | Any | Pembrolizumab and chemotherapy | 60 | 55 (42.0–68.0) | 13.0 (8.3–NR) | NR | 39 | Langer et al.47 |
| Chemotherapy alone | 63 | 29 (18.0–41.0) p = 0.0016 | 8.9 (4.4–10.3) p = 0.010 | NR p = 0.39 | 26 | |||||
| KEYNOTE-021 | Non-squamous | II | Any | Pembrolizumab and chemotherapy | 60 | 58 | 24.5 (9.7–36.3) | 34.5 (24.0–NR) | 39 | Awad et al.48 |
| Chemotherapy alone | 63 | 33 | 9.0 (6.2–15.2) HR: 0.54; (0.35–0.83) | 21.1 (14.9–35.6) HR: 0.71; (0.45–1.12) | 31 | |||||
| KEYNOTE-024 | Squamous or non- squamous | III | ⩾50 | Pembrolizumab | 154 | 44.8 (36.8–53.0) | 10.3 (6.3–NR) | 30.0 (18.3–NR) | 31.2 | Reck et al.49,50 |
| Chemotherapy | 151 | 27.8 (20.8–35.7) | 6.0 (4.2–6.2) p < 0.001 | 14.2 (9.8–19.0) p = 0.002 | 53.3 | |||||
| KEYNOTE-042 | Squamous or non- squamous | III | ⩾50 | Pembrolizumab | 299 | 39 | 7.1 (5.9–9.0) | 20.0 (15.4–24.9) | 18 | Mok et al.51 |
| Chemotherapy | 300 | 32 | 6.4 (6.1–6.9) p = 0.0170 | 12.2 (10.4–14.2) p = 0.0003 | 41 | |||||
| HOPE-001 | Squamous or non- squamous | Real-word study | ⩾50 | Pembrolizumab | 213 | 51.2 | 8.3 (6.0–10.7) | 17.8 (17.8–NR) | 18.3 | Tamiya et al.52 |
| CheckMate 012 | Squamous or non- squamous | I | Any | Nivolumab | 52 | 23 (12.0–52.0) | 3.6 (0.1–28.0) | 19.4 (0.2–35.8) | 19 | Gettinger et al.53 |
| CheckMate 012 | Squamous or non- squamous | I | Any | 2 weeks nivolumab plus 12 weeks ipilimumab | 38 | 47 (31–64) | NA | NR | 37 | Hellmann et al.54 |
| 2 weeks nivolumab plus 6 weeks ipilimumab | 40 | 38 (23–55) | NA | NR | 33 | |||||
| CheckMate 568 | Squamous or non- squamous | II | Any | Nivolumab (TMB ⩾10) | 48 | 44 | 7.1 (3.6–11.3) | NR | 29 | Ready et al.57 |
| Nivolumab (TMB <10) | 50 | 12 | 2.6 (1.4–5.4) | NR | ||||||
| CheckMate 026 | Squamous or non- squamous | III | ⩾5 | Nivolumab | 211 | 26 (20–33) | 4.2 (3.0–5.6) | 14.4 (11.7–17.4) | 18 | Carbone et al.58 |
| Chemotherapy | 212 | 33 (27–40) | 5.9 (5.4–6.9) p = 0.25 | 13.2 (10.7–17.1) HR: 1.01; (0.80–1.30) | 51 | |||||
| BIRCH | Squamous or non- squamous | NA | ⩾5 | Atezolizumab | 139 | 22 | 5.4 (3.0–6.9) | 20.1 (20.1–NR) | 40 | Peters et al.59 |
| IMpower150 | Non- squamous | III | Any | ACP | 402 | 49.2 | 7.0 | 18.6 | NA | Socinski et al.60 |
| BCP | 400 | 53.5 | 6.8 | 14.7 | 47.7 | |||||
| ABCP | 400 | 69.3 | 8.3 (p < 0.001) | 19.2 (p = 0.02) | 57.7 | |||||
| IMpower132 | Non- squamous | III | Any | APP | 292 | 49.6 | 7.6 (6.6–8.5) | 18.1 (13.0–NR) | 53.6 | Papadimitrakopoulou et al.61 |
| PP | 286 | 32.2 | 5.2 (4.3–5.6) p < 0.0001 | 13.6 (11.4–15.5) p = 0.0797 | 39.1 | |||||
| IMpower130 | Non- squamous | III | Any | Atezolizumab plus chemotherapy | 451 | 49.2 | 7.0 (6.2–7.3) | 18.6 (16.0–21.2) | 81.0 | Planchard et al.62 |
| Chemotherapy | 228 | 31.9 | 5.5 (4.4–5.9) p < 0.0001 | 13.9 (12.0–18.7) p = 0.033 | 71.0 | |||||
| IMpower131 | Squamous | III | Any | Atezolizumab + CnP | 343 | 49.7 | 6.3 | 14.2 | 69.2 | Jotte et al.63 |
| CnP | 340 | 41.0 | 5.6 (p = 0.0001) | 13.5 (p = 0.16) | 58.4 | |||||
| Impower110 | Squamous or non- squamous | III | ⩾50 | Atezolizumab | 107 | 38.3 | 8.1 | 20.2 (16.5–NR) | 33.9 | Herbst et al.64 |
| Chemotherapy | 98 | 28.6 | 5.0 HR: 0.63; (0.45–0.88) | 13.1 (7.4–16.5) p = 0.01) | 56.7 |
ABCP, atezolizumab plus BCP; AE, adverse event; ACP, atezolizumab plus carboplatin plus paclitaxel; APP, atezolizumab plus pemetrexed plus carboplatin or cisplatin; BCP, bevacizumab plus carboplatin plus paclitaxel; CI, confidence interval; CnP, carboplatin + nab-paclitaxel; HR, hazard ratio; mOS, median overall survival; mPFS, median progression-free survival; NA, not applicable; NSCLC, non-small-cell lung cancer; NR, not reached; ORR, objective response rate; PD-1, programmed cell-death protein 1; PD-L1, programmed cell-death ligand 1; PP, pemetrexed plus carboplatin or cisplatin; TMB, tumour mutational burden; TPS, tumour proportion score.