Source | Period | Sex and mean age | Prior-treatment* | Arm 1 (number) | Arm 2 (number) | Outcome† | Study design (registration information) |
Sequist et al, 2013 (America) [4] | 2009-2011 | M/F, 61.6 | not assigned | 40 mg/d afatinib (20) | 75 mg/m2 cisplatin + 500 mg/m2 pemetrexed every 3 weeks (15) | OS: HR, 1.14 (95% CI, 0.55-2.30); PFS: HR 0.54 (95% CI, 0.23-1.25) | phase II RCT (NCT01121393) |
Wu et al, 2014 (multi nations) [5] | 2010-2011 | M/F, 54.1 | not assigned | 40 mg/d afatinib (28) | 75 mg/m2 cisplatin + 1000 mg/m2 gemcitabine every 3 weeks (18) | OS: HR, 1.13 (95% CI, 0.56-2.26); PFS: HR 0.47 (95% CI, 0.18-1.21) | phase III RCT (NCT00949650) |
Scagliotti et al, 2015 (multi nations) [6] | 2011-2012 | M/F, 61.2 | not assigned, part with EGFR-TKI or MET-TKI-naive regimes history | 150 mg/d erlotinib + 720 mg/d tivantinib (56) | 150 mg/d erlotinib (53) | OS: HR, 0.72 (95% CI, 0.35-1.48) | phase III RCT (NCT01244191) |
Soria et al, 2015 (multinations) [7] | 2012-2013 | M/F, 59.0 | not assigned, part with chemotherapy-naive regimen history, CR or PR after at least 6 months first-line gefitinib | 250 mg/d gefitinib + 75 mg/m2 cisplatin and 500 mg/m2 pemetrexed (44) | 75 mg/m2 cisplatin and 500 mg/m2 pemetrexed every 3 weeks (31) | OS: HR, 1.55 (95% CI, 1.00-2.41); PFS: HR 0.80 (95% CI, 0.61-1.06) | phase III RCT (NCT01544179) |
Magnuson et al, 2016 (America) [8] | 2008-2014 | M/F,59.3 | not assigned | upfront 150 mg/d erlotinib followed by SRS/WBRT (17) | upfront SRS/WBRT followed by 150 mg/d erlotinib (33) | OS: HR, 2.48 (95% CI, 1.34-4.60); PFS: HR, 2.13 (95% CI, 1.57-2.69) | phase II RCT (NCT01763385) |
Park et al, 2016 (multinations) [9] | 2011-2013 | M/F, NA | not assigned | 40 mg/d afatinid (26) | 250 mg/d gefitinib (24) | PFS: HR, 0.73 (95% CI, 0.58-0.92) | phase II b RCT (NCT01466660) |
Schuler et al, 2016 (Germany) [10] | 2009-2012 | M/F, 57.3 | not assigned; part with WBRT history | 40 mg/d afatinid (48) | 75 mg/m2 cisplatin + 500 mg/m2 pemetrexed or 1000 mg/m2 gemcitabine every 3 weeks (33) | OS: HR, 1.14 (95% CI, 0.66-1.94); PFS: HR, 0.50 (95% CI, 0.27-0.95) | phase III RCT (NA) |
Fan et al, 2017 (China) [11] | 2011-2014 | M/F,58.0 | not assigned, part with platinum-based chemotherapy history | 375 mg/d icotinib + SRS/WBRT (WBRT (46) and SRS (10)) (56) | 375 mg/d icotinib alone (41) | OS: HR, 0.47 (95% CI, 0.24-0.95); PFS: HR, 0.63 (95% CI, 0.35-1.14) | phase II RCT (NCT01516983) |
Mok et al, 2017 (Multinations) [12] | 2014-2016 | M/F, 62.3 | not assigned | 80 mg/d osimertinib (93) | 500 mg/m2 pemetrexed + carboplatin or 75 mg/m2 cisplatin every 3 weeks (51) | PFS: HR, 0.32 (95% CI, 0.21-0.49) | phase III RCT (NCT02151981) |
Mok et al (2), 2017 (Multinations) [13] | 2012-2015 | M/F, NA | not assigned, precautionary premedication regimens (antiemetic, hydration, corticosteroid treatment) were taken to reduce toxicity in platinum group | 250 mg/d gefitinib + 75 mg/m2 cisplatin and 500 mg/m2 pemetrexed (44) | 75 mg/m2 cisplatin and 500 mg/m2 pemetrexed every 3 weeks (31) | OS: HR, 1.31 (95% CI, 0.97-1.77), PFS: HR, 0.79 (95% CI, 0.60-1.05) | phase III RCT (NCT01544179) |
Yang et al, 2017 (China) [14] | 2012-2016 | M/F, 57.5 | not assigned | 375 mg/d icotinib (85) | WBRT alone 10 fractions (73) | OS: HR, 0.93 (95% CI, 0.60-1.44), PFS: HR, 0.56 (95% CI, 0.36-0.90) | phase III RCT (NCT01724801) |
Zhu et al, 2017 (China) [15] | 2011-2015 | M/F, 56.0 | not assigned | 250 mg/d gefitinib or 150 mg/d erlotinib (66) | EGFR-TKI + SRS/WBRT (67)‡ | OS: HR, 1.82 (95% CI, 1.11-2.98), PFS: HR, 1.62 (95% CI, 1.07-2.45) | phase III RCT (approved by the institutional review board) |
Reungwetwattana et al, 2018 (multinations) [16] | 2015-2017 | M/F, 63.0 | not assigned | 80 mg/d osimertinib (61) | 250 mg/d gefitinib or 150 mg/d erlotinib (67) | PFS: HR, 0.48 (95% CI, 0.26-0.86) | phase III RCT (NCT02296125) |
Soria et al, 2018 (multinations) [17] | 2015-2017 | M/F, 64.0 | not assigned, part with definitive treatment or glucocorticoid therapy history§ | 80 mg/d osimertinib (53) | 250 mg/d gefitinib or 150 mg/d erlotinib (63) | PFS: HR, 0.47 (95% CI, 0.30-0.74) | phase III RCT (NCT02296125) |
Wu et al, 2018 (multinations) [18] | 2014-2016 | M/F, 58.0 | not assigned | 80 mg/d osimertinib (75) | cisplatin or 75 mg/m2 carboplatin + 500 mg/m2 Pemetrexed every 3 weeks (41) | PFS: HR, 0.32 (95% CI, 0.15-0.69) | phase III RCT (NCT02151981) |
Yang et al, 2018 (China) [19] | 2013-2016 | M/F, NA | not assigned, part with EGFR-TKI and brain RT-naive regimen history | 150 mg/d erlotinib + WBRT (55) | WBRT alone (54) | OS: HR, 0.91 (95% CI, 0.68-1.23); PFS: HR, 0.97 (95% CI, 0.74-1.28) | phase III RCT (NCT01887795) |
Saito et al, 2019 (Japan) [20] | 2015-2017 | M/F, 67.5 | not assigned | 150 mg/d erlotinib + bevacizumab 15mg/kg every 3 weeks (36) | 150 mg/d erlotinib (36) | PFS: HR, 0.78 (95% CI, 0.42-1.43) | phase III RCT (UMIN000017069) |
Ramalingam et al, 2019 (multinations) [21] | 2015-2019 | M/F, 64.0 | not assigned | 80 mg/d osimertinib (53) | 250 mg/d gefitinib or 150 mg/d erlotinib (63) | OS: HR, 0.83 (95% CI, 0.53-1.30) | phase III RCT (NCT02296125) |