Table 2. Randomised clinical trials conducted with tyrosine kinase inhibitors (TKI) in 2012 and 2013.
| First author [ref.] | Study name | Study phase | Population | Patients n | Treatment | RR (%) | p-value | PFS months | p-value | Survival | p-value |
| 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 |
RR: response rate; PFS: progression-free survival; EGFR: epidermal growth factor receptor; NEJ002: North East Japan 002; TOPICAL: Tarceva or Placebo in Clinically Advanced Lung Cancer; TORCH: Tarceva or Chemotherapy; TAILOR: Tarceva Italian Lung Optimization Trial; ATLAS: Avastin Tarceva Lung Adenocarcinoma Study; INFORM: Iressa in NSCLC for Maintenance; NCIC CTG BR13: National Cancer Institute of Canada Clinical Trials Group; FASTACT-2: First-Line Asian Sequential Tarceva and Chemotherapy Trial; NVALT: Nederlandse Vereniging van Artsen voor Longziekten Tuberculose; NSCLC: nonsmall cell lung cancer; ADC: adenocarcinoma; ALK: anaplastic lymphoma kinase; CDDP: cisplatin; GEM: gemcitabine; CBDCA: carboplatin; PTX: paclitaxel; DOC: docetaxel; PEM: pemetrexed; HR: hazard ratio ns: not statistically significant; NR: not reached. #: statistically significant; ¶: patients who responded to the combination of erlotinib and chemotherapy; +: patients who responded to chemotherapy alone.