TABLE 1.
Large randomized phase 3 trials of ICBs in squamous and nonsquamous NSCLC
| Study | N | Histology | Design | ORR | mPFS | mOS | HR for OS (95%CI) |
PD‐L1 subgroup HR for OS (95%CI) |
|---|---|---|---|---|---|---|---|---|
| First‐line | ||||||||
|
PD‐L1≥50% |
305 | Squamous/ Nonsquamous |
1. Pembro 2. Plat‐based Chemo |
44.8% 27.8% |
10.3 m 6.0 m |
30.0 m 14.2 m |
0.60 (0.41‐0.89) | — |
|
Keynote 042 12 PD‐L1≥1% |
1274 | Squamous/ Nonsquamous |
1. Pembro 2. Plat‐based Chemo |
27% 27% |
5.4 m 6.5 m | 16.7 m 12.1 m | 0.81 (0.71‐0.93) |
≥50%, 0.69 (0.56‐0.85) 1–49%, 0.92 (0.77‐1.11) |
|
CheckMate 026 12 PD‐L1≥5% |
423 | Squamous/ Nonsquamous |
1. Nivo 2. Plat‐based Chemo |
26% 33% |
4.2 m 5.9 m | 14.4 m 13.2 m | 1.02 (0.80‐1.30) | ≥50%, 0.90 (0.63‐1.29) |
| Keynote 407 13 | 559 | Squamous |
1. Pembro+Pacl/Nab‐Pacl+Carbo 2. Placebo+Pacl/Nab‐Pacl+Carbo |
57.9% 38.4% |
6.4 m 4.8 m | 15.9 m 11.3 m | 0.64 (0.49‐0.85) |
≥50%, 0.64 (0.37‐1.10) 1‐49%, 0.57 (0.36‐0.90) <1%, 0.61 (0.38‐0.98) |
| Keynote 189 14 | 616 | Nonsquamous |
1. Pembro+Pem+Plat 2. Placebo+Pem+Plat |
47.6% 18.9% |
8.8 m 4.9 m |
NR 11.3 m |
0.49 (0.38‐0.64) |
≥50%, 0.42 (0.26‐0.68) 1‐49%, 0.55 (0.34‐0.90) <1%, 0.59 (0.38‐0.92) |
| IMpower131 15 | 683 | Squamous |
1. Atezo+Nab‐Pacl+Carbo 2. Nab‐Pacl+Carbo |
49% 41% |
6.3 m 5.6 m | 14.0 m 13.9 m | 0.96 (0.78‐1.18) |
HR for PFS TC3 or IC3, 0.44 (0.27‐0.71) TC1/2 or IC1/2, 0.70 (0.53‐0.92) TC0 and IC0, 0.81 (0.64‐1.03) |
| IMpower132 16 | 578 | Nonsquamous |
1. Atezo+Pem+Plat 2. Placebo+Pem+Plat |
47% 32% |
7.6 m 5.2 m | 18.1 m 13.6 m | 0.81 (0.64‐1.03) |
HR for PFS TC3 or IC3, 0.46 (0.22‐0.96) TC1/2 or IC1/2, 0.80 (0.56‐1.16) TC0 and IC0, 0.45 (0.31‐0.64) |
| IMpower150 17 | 800 | Nonsquamous |
1. Atezo+Bev+Pacl+Carbo 2. Bev+Pacl+Carbo |
63.5% 48.0% |
8.3 m 6.8 m | 19.2 m 14.7 m | 0.78 (0.64‐0.96) |
TC3 or IC3, 0.39 (0.25‐0.60) TC1/2 or IC1/2, 0.56 (0.41–0.77) TC0 and IC0, 0.77 (0.61–0.99) |
| CheckMate 227 18 | 1166 | Squamous/ Nonsquamous |
1. Nivo+ipi 2. Chemo |
‐ | ‐ |
17.1 m 13.9 m |
0.73 (0.64–0.84) |
≥50%, 0.70 (0.55–0.90) 1–49%, 0.94 (0.75–1.18) <1%, 0.62 (0.49–0.79) |
| Second‐line and beyond | ||||||||
|
Keynote 010 19 PD‐L1≥1% |
1034 | Squamous/ Nonsquamous |
1. Pembro 2 mg/kg 2. Pembro 10 mg/kg 3. Docetaxel |
18% 18% 9% |
3.9 m 4.0 m 4.0 m |
10.4 m 12.7 m 8.5 m |
1:3 0.71 (0.58–0.88) 2:3 0.61 (0.49–0.75) |
≥50%, 0.53 (0.40–0.70) 1–49%, 0.76 (0.60–0.96) |
| OAK 20 | 1225 | Squamous/ Nonsquamous |
1. Atezo 2. docetaxel |
14% 13% |
2.8 m 4.0 m |
13.8 m 9.6 m |
0.73 (0.62–0.87) |
TC3 or IC3, 0.41 (0.27–0.64) TC1/2/3 or IC1/2/3, 0.74 (0.58–0.93) TC0 and IC0, 0.75 (0.59–0.96) |
| CheckMate 017 21 | 272 | Squamous |
1. Nivo 2. Docetaxel |
20% 9% |
3.5 m 2.8 m |
9.2 m 6.0 m |
0.59 (0.44–0.79) |
≥10%, 0.50 (0.28–0.89) ≥5%, 0.53 (0.31–0.89) ≥1%, 0.69 (0.45–1.05) |
| CheckMate 057 22 | 582 | Nonsquamous |
1. Nivo 2. Docetaxel |
19% 12% |
2.3 m 4.2 m |
12.2 m 9.4 m |
0.73 (96%CI, 0.59–0.89) |
‐ |
| Consolidation | ||||||||
| PACIFIC 23 , 24 | 709 | Squamous/ Nonsquamous |
1. CRT+Durva 2. CRT+Placebo |
28.5% 20% |
17.2 m 5.6 m |
NR 28.7 m |
0.68 (99.73%CI, 0.47–0.997) |
HR for PFS ≥25%, 0.41 (0.26–0.65) <25%, 0.59 (0.43–0.82) |
Abbreviations: Atezo, atezolizumab; Bev, bevacizumab; Carbo, carboplatin; Chemo, chemotherapy; CI, confidential interval; CRT, chemoradiotherapy; Durva, durvalumab; HR, hazard ratio; Nab‐Pacl, nanoparticle albumin‐bound–paclitaxel; Nivo, nivolumab; ORR, objective response rate; OS, overall survival; Pacl, paclitaxel; Pem, pemetrexed; Pembro, pembrolizumab; PFS, progression‐free survival; Plat, platinum.