Table 2.
Pivotal randomised controlled trials of Epidermal Growth Factor Receptor (EGFR) TKIs in patients with Stage IIIB/IV non-small cell lung cancer.
| Author, Year Trial Name |
Country | Population | Intervention n |
Control n |
Median Overall Survival (Months) HR (95% CI) |
Median Progression-Free Survival (Months) HR (95% CI) |
Response Rate |
|---|---|---|---|---|---|---|---|
| First line treatment | |||||||
| Mok, 2009 [30,31] IPASS |
East Asia | Non-smokers Phase III |
Gefitinib 609 |
Carboplatin and paclitaxel 608 |
18.6 vs. 17.3 HR 0.91 (0.76 to 1.10) |
5.7 vs. 5.8 HR 0.75 (0.65 to 0.85) |
43% vs. 32.2% |
| Subgroup: EGFR mutant Subgroup: EGFR wildtype |
HR 0.78 (0.50 to 1.20), NS HR 1.38 (0.92 to 2.09), NS |
HR 0.48 (0.36 to 0.64) HR 2.85 (2.05 to 3.98) |
71.2% vs. 47.3% 1.1% vs. 23.5% |
||||
| Mitsudomi, 2010 [5,32] WJTOG3405 |
Japan |
EGFR mutation + Phase III |
Gefitinib 86 |
Cisplatin and docetaxel 86 |
38.4 vs. 37.3 HR 1.25 (0.88 to 1.78) |
9.2 vs. 6.3 HR 0.49 (0.34 to 0.71) |
62.1% vs. 32.2% |
| Maemondo, 2010 [33,38] NEJ002 |
Japan |
EGFR mutation + Phase III |
Gefitinib 115 |
Carboplatin & paclitaxel 115 |
27.7 vs. 26.6 HR 0.89 (0.63 to 1.24), NS |
10.8 vs. 5.4 HR 0.32 (0.24 to 0.44) |
73.7% vs. 30.7% |
| Zhou, 2011 [34,35] OPTIMAL/CTONG-0802 |
China |
EGFR mutation + Phase III |
Erlotinib 82 |
Carboplatin and gemcitabine 72 |
22.8 vs. 27.2 HR 1.19 (0.83 to 1.71), NS |
13.1 vs. 4.6 HR 0.16 (0.10 to 0.26) |
83% vs. 36% |
| Rosell, 2012 [36] EURTAC |
Europe |
EGFR mutation + Phase III |
Erlotinib 86 |
Cisplatin and docetaxel or gemcitabine 87 |
19.3 vs. 19.5 HR 1.04 (0.65 to 1.68), NS |
9.7 vs. 5.2 HR 0.37 (0.25 to 0.54) |
58% vs. 15% |
| Wu, 2015 [6] ENSURE |
Asia |
EGFR mutation + Phase III |
Erlotinib 110 |
Cisplatin and gemcitabine 107 |
26.3 vs. 25.5 HR 0.91 (0.63 to 1.31), NS |
11.0 vs. 5.5 HR 0.34 (0.22 to 0.51) |
62.7% vs. 33.6% |
| Sequist, 2013 [7,39] LUX-Lung 3 |
International |
EGFR mutation + Phase III |
Afatinib 230 |
Cisplatin and pemetrexed 115 |
28.2 vs. 28.2 HR 0.88 (0.66 to 1.17), NS |
11.1 vs. 6.9 HR 0.58 (0.43 to 0.78) |
56% vs. 23% |
| Wu, 2014 [7,40] LUX-Lung 6 |
Asia |
EGFR mutation + Phase III |
Afatinib 242 |
Cisplatin and gemcitabine 122 |
23.1 vs. 23.5 HR 0.93 (0.72–1.22), NS |
11 vs. 5.6 HR 0.28 (0.20 to 0.39) |
66.9% vs. 23% |
| Park, 2016 [41] LUX-Lung 7 [42] |
International |
EGFR mutation + Phase II |
Afatinib 160 |
Gefitinib 159 |
27.9 vs. 24.5 HR 0.86 (0.66 to 1.12), NS |
11.0 vs. 10.9 HR 0.73 (0.57 to 0.95) |
70% vs. 56% |
| Wu, 2017 ARCHER 1050 [43,44] |
Asia |
EGFR mutation + Phase III |
Dacomitinib 227 |
Gefitinib 225 |
34.1 vs. 26.8 HR 0.76 (0.58 to 0.99) |
14.7 vs. 9.2 HR 0.59 (0.47 to 0.74) |
75% vs. 72% |
| Shi, 2017 CONVINCE [37] |
China |
EGFR mutation + Phase III |
Icotinib 148 |
Cisplatin and pemetrexed 137 |
Data immature | 11.2 vs. 7.9 HR 0.61 (0.43 to 0.87) |
64.8% vs. 33.8% |
| Soria, 2018 [45] FLAURA |
International |
EGFR mutation + Phase III |
Osimertinib 279 |
Gefitinib or erlotinib 277 |
Data immature | 18.9 vs. 10.2 HR 0.46 (0.37 to 0.57) |
80% vs. 76% (NS) |
| Second line treatment | |||||||
| Mok, 2017 [46] AURA3 |
International | T790M mutation + PD after EGFR TKI Phase III |
Osimertinib 279 |
Platinum and pemetrexed 140 |
Data immature | 10.1 vs. 4.4 HR 0.30 (0.23 to 0.41) |
71% vs. 31% |
HR: hazard ratio; NS: not significant; PD: progressive disease. IPASS: Iressa Pan-Asia Study; WJTOG: West Japan Thoracic Oncology Group; NEJ: North East Japan Study Group; CTONG: Chinese Thoracic Oncology Group; EURTAC: European Randomised Trial of Tarceva vs Chemotherapy. All trials used consistent dosing of gefitinib 250 mg, erlotinib 150 mg, afatinib 40 mg daily, dacomitinib 45 mg daily, icotinib 125 mg three times a day, and osimertinib 80 mg daily.