Table 3.
Efficacy of anti-PD-1/PD-L1 agents for advanced NSCLC in second line and third line.
| Study | Histologies | 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 3–4 AE% | Refences |
|---|---|---|---|---|---|---|---|---|---|---|
| Checkmate 017 (second) | Squamous | III | Any | Nivolumab | 135 | 20 (14–28) | 3.5 (2.1–4.0) | 9.2 (7.3–13.3) | 7 | Brahmer et al.69; Reck et al.70 |
| Docetaxel | 137 | 9 (5–15) p = 0.008 | 2.8 (2.1–3.5) p < 0.01 | 6.0 (5.1–7.3) p < 0.001 | 55 | |||||
| Checkmate 057 (second) | Non-squamous | III | Any | Nivolumab | 292 | 19 (15–24) | 2.3 (2.2–3.3) | 12.2 (9.7–15.0) | 10 | Borghaei et al.71; Reck et al.72 |
| Docetaxel | 290 | 12 (7–17) p = 0.02 | 4.2 (3.5–4.9) p = 0.39 | 9.4 (8.1–10.7) p = 0.002 | 54 | |||||
| Checkmate 078 (second) | Squamous or non- squamous | III | Any | Nivolumab | 338 | 16.6 (12.2–21.0) | 2.8 (2.4–3.4) | 12.0 (10.4–14.0) | 10 | Wu et al.74 |
| Docetaxel | 166 | 4.2 (1.7–8.5) p < 0.0001 | 2.8 (1.6–2.9) p = 0.0147 | 9.6 (7.6–11.2) p = 0.0006 | 48 | |||||
| Keynote-010 (second) | Squamous or non- squamous | II/III | ⩾1% | Pembrolizumab 2 mg/kg | 345 | 18 | 3.9 (3.1–4.1) p = 0.07 | 10.4 (9.4–11.9) p = 0.0008 | 13 | Herbst et al.77,78 |
| Pembrolizumab 10 mg/kg | 346 | 18 | 4.0 (2.7–4.3) p = 0.004 | 12.7 (10.0–17.3) p < 0.0001 | 16 | |||||
| Docetaxel | 343 | 9 (p = 0.0005) | 4.0 (3.1–4.2) | 8.5 (7.5–9.8) | 35 | |||||
| ⩾50% | Pembrolizumab 2 mg/kg | 139 | 30 | 5.0 (4.0–6.5) p = 0.0002 | 14.9 (10.4–NR) p = 0.0002 | NA | ||||
| Pembrolizumab 10 mg/kg | 151 | 29 | 5.2 (4.1–8.1) p < 0.0001 | 17.3 (11.8–NR) p < 0.0001 | NA | |||||
| Docetaxel | 152 | 8 (p < 0.0001) | 4.1 (3.6–4.3) | 8.2 (6.4–10.7) | NA | |||||
| Keynote-025 (second) | Squamous or non- squamous | Ib | ⩾1% | Pembrolizumab | 38 | 22 (10–38) | 3.9 (2.0–6.2) | 19.2 (8.0–26.7) | 29 | Nishio et al.79 |
| ⩾50% | 12 | 27 (6–61) | 4.1 (1.6–19.1) | 17.9 (5.9–NR) | NA | |||||
| Keynote-021 (⩾2) | NSCLC | I/II | Any | Pembrolizumab plus ipilpmumab | 44 | 30 | 4.1 (1.4–5.8) | 10.9 (6.1–23.7) | 29 | Gubens et al.80 |
| OAK (second) | Squamous or non- squamous | III | Any | Atezolizumab | 425 | 14 | 2.8 (2.6–3.0) | 13.8 (11.8–15.7) | 15 | Rittmeyer et al.81; von Pawel et al.82 |
| Docetaxel | 425 | 13 | 4.0 (3.3–4.2) p = 0.049 | 9.6 (8.6–11.2) p = 0.0003 | 43 | |||||
| POPLAR (second) | Squamous or non- squamous | II | Any | Atezolizumab | 144 | 17 (11.0–23.8) | 2.7 | 12.6 (9.7–16.4) | 11 | Fehrenbacher et al.83 |
| Docetaxel | 143 | 15 (9.3–21.4) | 3.0 HR: 0.94; (0.72–1.23) | 9.7 (8.6–12.0) p = 0.04 | 39 | |||||
| BIRCH (second) | Squamous or non- squamous | NA | ⩾5% | Atezolizumab | 268 | 19 | 2.8 (1.5–3.9) | 15.5 (12.3–NR) | NA | Peters et al.59 |
| BIRCH (third) | Squamous or non- squamous | NA | ⩾5% | Atezolizumab | 252 | 18 | 2.8 (1.5–3.9) | 13.2 (10.3–17.5) | NA | Peters et al.59 |
| ATLANTIC (third) | Squamous or non- squamous | II | ⩾25% | EGFR and ALK positivity (durvalumab) | 74 | 12.2 (5.7–21.8) | 1.9 (1.803.6) | 13.3 (8.1–NR) | 6 | Garassino et al.87 |
| EGFR and ALK negativity (durvalumab) | 146 | 16.4 (10.8–23.5) | 3.3 (1.9–3.7) | 10.9 (8.6–13.6) | 9 | |||||
| ⩾90% PD-L1 expression (durvalumab) | 68 | 30.9 (20.2–43.3) | 2.4 (1.8–5.5) | NR (9.5–NR) | 18 | |||||
| ARCTIC (⩾3) | Squamous or non- squamous | III | ⩾25 | durvalumab | 62 | 35.5 | 3.8 (1.9–5.6) | 11.7 (8.2–17.4) | 9.7 | Planchard et al.88 |
| Standard of care | 64 | 12.5 | 2.2 (1.9–3.7) HR: 0.71 (0.49–1.04) | 6.8 (4.9–10.2) HR: 0.63 (0.42–0.93) | 44.4 | |||||
| <25 | Durvalumab + tremelimumab | 174 | 14.9 | 3.5 (2.3–4.6) | 11.5 (8.7–14.1) | 22.0 | ||||
| Standard of care | 118 | 6.8 | 3.5 (1.9–3.9) p = 0.056 | 8.7 (6.5–11.7) p = 0.109 | 36.4 |
AE, adverse event; ALK, anaplastic lymphoma kinase; CI, confidence interval; EGFR, epidermal growth-factor receptor; 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; TMB, tumour mutational burden; TPS, tumour proportion score.