First-line treatment | | | | | | | | | | | |
Inoue [26] | NEJ002 | III | Stage IIIB/IV NSCLC | 114 | CBDCA/PTX | | | 5.4 | <0.001 | 26.6 months | 0.483 |
| | | EGFR muted | 114 | Gefitinib | | | 10.8 | | 27.7 months | |
Lee [27] | TOPICAL | III | Unselected stage IIIB/IV NSCLC | 350 | Erlotinib | 4.0 | | 2.8 | 0.019 | 3.7 months | 0.46 |
| | | Unsuitable for conventional chemotherapy | 320 | Placebo | 2.0 | | 2.6 | | 3.6 months | |
Gridelli [28] | TORCH | III | Unselected stage IIIB/IV NSCLC | 380 | Erlotinib | 8.7 | <0.001 | 6.4 | <0.05# | 8.7 months | <0.05# |
| | | Unselected stage IIIB/IV NSCLC | 380 | CDDP-GEM | 25.6 | | 8.9 | | 11.6 months | |
Sequist [29] | LUX-LUNG3 | III | Stage IIIB/IV ADC EGFR muted | 230 | Afatinib | 56.0 | 0.001 | 11.1 | 0.001 | 16.6 months | 0.60 |
| | | Stage IIIB/IV ADC EGFR muted | 115 | CDDP-PEM | 23.0 | | 6.9 | | 14.8 months | |
Second-line treatment | | | | | | | | | | | |
Garassino [30] | TAILOR | III | Advanced NSCLC | 110 | DOC | 15.5 | 0.003 | 2.9 | 0.02 | 8.2 months | 0.05 |
| | | Wild-type EGFR | 109 | Erlotinib | 3.0 | | 2.4 | | 5.4 months | |
Sun [31] | CONSORT | III | Asian never-smoker stage IIIB/IV ADC | 68 | Gefitinib | 58.8 | <0.001 | 9 | 0.0013 | 22.2 months | 0.37 |
| | | Asian never-smoker stage IIIB/IV ADC | 67 | PEM | 22.4 | | 3 | | 18.9 months | |
| | | EGFR muted | | | | | HR 0.30 | 0.005 | | |
| | | Wild-type EGFR | | | | | HR 0.56 | 0.099 | | |
Lee [32] | | IIR | Stage III/IV never-smokers non-squamous NSCLC | 76 | PEM-erlotinib | 44.7 | <0.001 | 7.4 | 0.003 | 20.5 months | 0.194 |
| | | Stage III/IV never-smokers non-squamous NSCLC | 82 | Erlotinib | 29.3 | | 3.8 | | 22.8 months | |
| | | Stage III/IV never-smokers non-squamous NSCLC | 80 | PEM | 10.0 | | 4.4 | | 17.7 months | |
Karamapeazis [33] | | III | Unselected stage IIIB/IV NSCLC | 166 | PEM | 11.4 | 0.469 | 2.9 | 0.136 | 10.1 months | 0.986 |
| | | Unselected stage IIIB/IV NSCLC | 166 | Erlotinib | 9.0 | | 3.6 | | 8.2 months | |
Shaw [34] | | III | ALK positive advanced NSCLC | 173 | Crizotinib | 65.0 | <0.001 | 7.7 | <0.001 | 20.3 months | 0.54 |
| | | ALK positive advanced NSCLC | 174 | PEM or DOC | 20.0 | | 3.0 | | 22.8 months | |
Maintenance treatment | | | | | | | | | | | |
Perol [24] | | III | Unselected stage IIIB/IV NSCLC nonprogressing after 4 cycles of CDDP-GEM | 155 | Observation | | | 1.9 | | 10.8 months | |
| | | Unselected stage IIIB/IV NSCLC nonprogressing after 4 cycles of CDDP-GEM | 154 | GEM | | | 3.8 | <0.001 | 12.1 months | 0.37 |
| | | Unselected stage IIIB/IV NSCLC nonprogressing after 4 cycles of CDDP-GEM | 155 | Erlotinib | | | 2.9 | 0.003 | 11.4 months | 0.30 |
Johnson [35] | ATLAS | III | Unselected stage IIIB/IV NSCLC nonprogressing after 4 cycles of chemotherapy-bevacizumab | 373 | Bevacizumab | | | 3.7 | <0.001 | 13.3 months | 0.53 |
| | | Unselected stage IIIB/IV NSCLC nonprogressing after 4 cycles of chemotherapy-bevacizumab | 370 | Bevacizumab-erlotinib | | | 4.8 | | 14.4 months | |
Zhang [36] | INFORM | III | Unselected stage IIIB/IV NSCLC nonprogressing after 4 cycles of platinum doublet | 148 | Gefitinib | 24.0 | 0.0001 | 4.8 | <0.001 | 18.7 months | 0.26 |
| | | Unselected stage IIIB/IV NSCLC nonprogressing after 4 cycles of platinum doublet | 148 | Observation | 1.0 | | 2.6 | | 16.9 months | |
| | | EGFR muted | | | | | HR 0.17 | <0.05# | | |
| | | Wild-type EGFR | | | | | HR 0.86 | ns | | |
Goss [37] | NCIC CTG BR19 | III | Unselected completely resected stage I–IIIA NSCLC | 251 | Gefitinib | | | | | 5.1 years | 0.14 |
| | | Unselected completely resected stage I–IIIA NSCLC | 252 | Observation | | | | | NR | |
TKI intercalated with chemotherapy | | | | | | | | | | | |
Wu [38] | FASTACT-2 | III | Unselected stage IIIB/IV NSCLC and chemotherapy (platinum-GEM); first line | 226 | Erlotinib | 42.9 | <0.001 | 10.0 | <0.001 | 18.3 months | 0.04 |
| | | Unselected stage IIIB/IV NSCLC and chemotherapy (platinum-GEM); first line | 225 | Placebo | 18.2 | | 7.4 | | 15.2 months | |
| | | EGFR muted | | | 84¶/15+ | <0.001 | HR 0.25 | <0.001 | HR 0.48 | 0.009 |
| | | Wild-type EGFR | | | 26¶/19+ | 0.35 | HR 0.97 | 0.85 | HR 0.77 | 0.16 |
Aerts [39] | NVALT-10 | IIR | Unselected advanced NSCL; salvage chemotherapy | 115 | Erlotinib | 7 | | 4.9 | 0.06 | 5.5 months | 0.01 |
| | | Unselected advanced NSCL; salvage chemotherapy | 116 | Erlotinib+PEM or DOC | 13 | | 6.1 | | 7.8 months | |
Salvage TKI after failure of previous EGFR TKI | | | | | | | | | | | |
Miller [40] | LUX-LUNG1 | IIB/III | Stage IIIB/IV ADC | 390 | Afatinib | 7.0 | 0.007 | 3.3 | <0.0001 | 10.8 months | 0.74 |
| | | Stage IIIB/IV ADC | 195 | Placebo | <1.0 | | 1.1 | | 12.0 months | |