Table 2.
Results of landmark phase III trials evaluating Immune Checkpoint Inhibitors in metastatic non-small-cell lung cancer
| Clinical Trial/Phase | Patients | Line of treatment | Treatment | No. of pts | ORR (%) | Median PFS (months) | HR (95% CI); P | Median OS (months) | HR (95% CI); P |
|---|---|---|---|---|---|---|---|---|---|
| NCT01642004 (Checkmate017) | Metastatic squamous NSCLC | Second line | Nivolumab Docetaxel |
135 137 |
20.0 8.8 |
3.5 2.8 |
HR=0.62 (0.47–0.81) P<0.001 |
9.2 6.0 |
HR=0.59 (0.43–0.81) P<0.001 |
| NCT01673867 (Checkmate057) | Metastatic nonsquamous NSCLC | Second or third line | Nivolumab Docetaxel |
292 290 |
19.2 12.4 |
2.3 4.2 |
HR=0.92 (0.77–1.11) P=0.3932 |
12.2 9.4 |
HR=0.73 (0.59–0.89) P=0.002 |
| NCT 01905657 (KEYNOTE010) | Metastatic NSCLC with PD-L1 positive | More than second line | Pembrolizumab (2 mg/kg) Pembrolizumab (10 mg/kg) Docetaxel |
344 346 343 |
18.0 18.5 9.3 |
3.9 4.0 4.0 |
HR=0.88 (0.73–1.04) P=0.06758; HR=0.79 (0.66–0.94) P<0.001; |
10.4 12.7 8.5 |
HR=0.71 (0.58–0.88) P<0.001 HR=0.61 (0.49–0.75) P=0.00462 |
| NCT 02142738 (KEYNOTE024) | Metastatic NSCLC with PD-L1 ≥50% | First line | Pembrolizumab SOC Chemotherapy |
154 151 |
44.8 27.8 |
-- | - | 30.0 14.2 |
HR=0.63 (0.47–0.86) P=0.002 |
| NCT 02220894 (KEYNOTE042) | PD-L1 positive advanced or metastatic NSCLC | First line | Pembrolizumaba SOC treatmenta Pembrolizumabb SOC treatmentb Pembrolizumabc SOC treatmentc |
299 300 413 405 637 637 |
39.5 32.0 33.4 28.9 27.3 26.5 |
7.1 6.4 6.2 6.6 5.4 6.5 |
HR=0.81 (0.67–0.99) P=0.0170; HR=0.94 (0.80–1.11) P=0.2331; HR=1.07 (0.94–1.21) P=0.8445; |
20.0 12.2 17.7 13.0 16.7 12.1 |
HR=0.69 (0.56–0.85) P=0.0003 HR=0.77 (0.64–0.92) P=0.0020 HR=0.81 (0.71–0.93) P=0.0018 |
| NCT 02775435 (KEYNOTE407) | Metastatic squamous NSCLC | First line | Pembrolizumab+PC PC |
278 281 |
57.9 38.4 |
6.4 4.8 |
HR=0.56 (0.45–0.70) P<0.001; |
15.9# 11.3 |
HR=0.64 (0.49–0.85) P=0.0008 |
| NCT 02578680 (KEYNOTE189) | Metastatic non-squamous NSCLC | First line | Pembro+AC/AP Placebo+AC/AP |
410 206 |
47.6 18.9 |
8.8 4.9 |
HR=0.52 (0.43–0.64) P<0.001 | NA 11.3 |
HR=0.49 (0.38–0.64) P<0.001 |
| NCT 02008227 (OAK) | Pre-treated LA or metastatic NSCLC | Second or third line | Atezolizumab Docetaxel |
612 613 |
13.6 13.4 |
2.8 4.0 |
HR=0.93 (0.81–1.08) P=0.3596 |
13.8 9.6 |
HR=0.73 (0.62–0.86) P<0.001 |
| NCT 02366143 (IMpower150) | Stage IV NSCLC | First line | ACPd ABCPd BCPd |
402 400 400 |
40.6 56.4 40.2 |
6.7 8.4 6.8 |
HR=0.91 (0.78–1.06) HR=0.59 (0.50–0.69) |
19.4 19.8 14.9 |
HR=0.85 (0.71–1.03) HR=0.76 (0.63–0.93) |
| NCT 02367781 (IMpower130) | Metastatic non-squamous NSCLC | First line | Atezo+Nab-PacC Nab-PacC |
483 240 |
-- | 7.0 5.5 |
HR=0.64 (0.54–0.77) P<0.001 |
18.6 13.9 |
HR=0.79 (0.64–0.98) P=0.0331 |
| NCT 02367794 (IMpower131) | Stage IV squamous NSCLC | First line | Atezo+PacC Atezo+Nab-PacC Nab-PacC |
338 343 340 |
-32 16 |
NR 6.3 5.6 |
HR=0.72 (0.60–0.85) P＝0.0001 |
-14.0 13.9 |
HR=0.96 (0.78–1.18) P=0.6931 |
| NCT 02657434 (IMpower132) | Stage IV non-squamous NSCLC | First line | Atezo+Cis/Car+Pem Cis/Car+Pem |
292 286 |
47 32 |
7.6 5.2 |
HR=0.60 (0.49–0.72) P<0.0001 |
18.1 13.6 |
HR=0.81 (0.64–1.03) P=0.0797 |
Notes: #OS upper limit not reached; aPatients with PD-L1 Tumor Proportion Score≥50%; bPatients with Tumor Proportion Score≥20%; cPatients with Tumor Proportion Score≥1%; dIntention-to-treat population.
Abbreviations: SOC, standard of care; NA, median OS not reached; LA, locally advanced; ACP, Atezolizumab + Carboplatin + Paclitaxel; ABCP, Atezolizumab + Bevacizumab + Carboplatin + Paclitaxel; BCP, Bevacizumab + Carboplatin + Paclitaxel; PC, nab-paclitaxel or paclitaxel + carboplatin; Cis/Car, Cisplatin or Carboplatin; NR, not reached.