Table 1.
Seminal studies of immune checkpoint inhibitors in NSCLC
| Study name | Phase | Population | Line of treatment | Design | SOC Outcome (95% CI) | Intervention Outcome (95% CI) | Hazard ratio (95% CI; P value) |
|---|---|---|---|---|---|---|---|
| Later line metastatic disease | |||||||
| CheckMate 017 | III | Squamous | 2nd or later | Nivolumab vs. docetaxel | mOS 6.0 months (5.1–7.3) |
mOS 9.2 months (7.3–12.6) | 0.62 (0.47–0.80) |
| CheckMate 057 | III | Nonsquamous | 2nd or later | Nivolumab vs. docetaxel | mOS 12.2 months (9.5–15.1) |
mOS 9.5 months (8.1–10.7) | 0.75 (0.63–0.91) |
| KEYNOTE-010 | II/III | NSCLC PD-L1 TPS ≥ 1% |
2nd or later | Pembrolizumab 2 mg/kg or 10 mg/kg vs. docetaxel | mOS 8.5 months (7.5–9.8) |
mOS 2 mg/kg 10.4 months (9.4–11.9) mOS 10 mg/kg 12.7 months (10.0–17.3) |
2 mg/kg vs. docetaxel: 0.71 (0.58–0.88); P=0.0008 10 mg/kg vs. docetaxel: 0.61 (0.49–0.75); P<0.0001 |
| POPLAR | II | NSCLC | 2nd or later | Atezolizumab vs. docetaxel | mOS 9.7 months (8.6–12.0) |
mOS 12.6 months (9.7–16.4) |
0.73 (0.53–0.99); P=0.04 |
| OAK | III | NSCLC | 2nd or later | Atezolizumab vs. docetaxel | mOS 9.6 months (8.6–11.2) |
mOS 13.8 months (11.8–15.7) |
0.73 (0.62–0.87); P=0.0003 |
| First line metastatic disease | |||||||
| KEYNOTE-024 | III | NSCLC PD-L1 TPS ≥ 50% |
Previously untreated | Pembrolizumab vs. chemotherapy | mOS 14.2 months (9.8–19.0) |
mOS 30.0 months (18.3-NR) |
0.63 (0.47–0.86); P=0.002 |
| KEYNOTE-042 | III | NSCLC PD-L1 TPS ≥ 1% |
Previously untreated | Pembrolizumab vs. chemotherapy | mOS 12.1 months (11.3–13.3) |
mOS 16.7 months (13.9–19.7) |
0.85 (0.71–0.93); P=0.0018 |
| CheckMate 026 | III | NSCLC PD-L1 TPS ≥ 1% |
Previously untreated | Nivolumab vs. chemotherapy | mOS 13.2 months (10.7–17.1) |
mOS 14.4 months (11.7–17.4) |
1.02 (0.80–1.30) |
| MYSTIC | III | NSCLC OS reported for PD-L1 TPS ≥ 25% |
Previously untreated | Durvalumab vs. Durvalumab + Tremelimumab vs. Chemotherapy | mOS 12.9 months (10.5–15.0) | mOS 16.3 months D (12.2–20.8) OS 11.9 months D +Tr (9.9–17.7) |
D vs. chemo: 0.76 (.56–1.02) D + Tr vs. chemo: 85 (0.61–1.17) |
| First line chemotherapy-checkpoint inhibitor combinations | |||||||
| KEYNOTE-189 | III | Nonsquamous | Previously untreated | C/Pem +/− pembrolizumab vs. placebo | 12 month OS 49.4% (42.1–56.2) |
12 month OS 69.2% (64.1–73.8) |
0.49 (0.38–0.64); P<0.001 |
| IMpower 150 | III | Nonsquamous; allowed EGFR/ALK alterations | Previously untreated | B/C/Pac +/− atezolizumab | mOS 14.7 months (13.3–16.9) |
mOS 19.2 months (17.0–23.8) |
0.78 (0.64–0.96); P=0.02 |
| IMpower 132 | III | Nonsquamous | Previously untreated | Pem/P +/− atezolizumab | mPFS 5.2 months (4.3–5.6) |
mPFS 7.6 months (6.6–8.5) |
0.60 (0.49–0.73); P<0.0001 |
| KEYNOTE-407 | III | Squamous | Previously untreated | C/T +/− pembrolizumab | mOS 11.3 months (9.5–14.8) |
mOS 15.9 months (13.2-NR) |
0.64 (0.49–0.85); P<0.001 |
| IMpower 131 | III | Squamous | Previously untreated | C/Nab +/− atezolizumab | mPFS 5.6 months (5.5–5.7) |
mPFS 6.3 months (5.7–7.1) |
0.715 (0.603–0.848); P=0.0001 |
| Adjuvant setting | |||||||
| PACIFIC | III | Stage III NSCLC | After definitive chemoRT | Durvalumab vs. placebo | 24 month OS 55.6% (48.9–61.8) |
24 month OS 66.3% (61.7–71.4) |
0.68 (99.73% CI 0.47–0.997); P=0.0025 |
C, carboplatin; chemoRT, chemoradiation; B, bevacizumab; D, durvalumab; mOS, median overall survival; Nab, nab-paclitaxel; NSCLC, non-small cell lung cancer; NR, not reached; P, platinum; Pac, paclitaxel; Pem, pemetrexed; T, taxane; Tr, tremilimumab