Table 1. Response rates to second and third generation EGFR TKIs in clinical trials.
| Agent | Study | Prior chemo-therapy | Prior EGFR TKI therapy | EGFR mutation required | No. of pts with EGFR mutation | ORR (in all pts, %) | No. pts with T790M | ORR (in T790M+ pts, %) |
|---|---|---|---|---|---|---|---|---|
| Second generation TKI | ||||||||
| Neratinib | NCT00266877 (127) | Yes & no | Yes & no | No | 91 | 3 | 12 | 0 |
| Afatinib | LUX-Lung 3 (128) | No | No | Yes | 345 | 56 | NR | NR |
| LUX-Lung 6 (129,130) | No | No | Yes | 242 | 67 | NR | NR | |
| LUX-Lung 2 (131) | Yes & no | No | Yes | 129 | 61 | 1 | NR | |
| LUX-Lung 1 (132) | Yes | ≥12 weeks E/G | No | 62 | 7 | 4 | NR | |
| LUX-Lung 4 (133) | Yes | ≥12 weeks E/G | No | 56 | 8 | 2 | NR | |
| LUX-Lung 5 (134) | Yes | ≥12 weeks A | No | NR | 32 | NR | NR | |
| Afatinib + cetuximab | NCT01090011 (135) | Yes | Yes | Yes | 126 | 29 | 71 | 32 |
| Dacomitinib | ARCHER 1009 (136) | Yes | Yes | No | 47 | 11 | NR | NR |
| BR26 (137) | Yes | Yes | No | 157 | 7 | NR | NR | |
| Third generation TKI | ||||||||
| AZD9291 | NCT01802632 (138) | Yes | Yes | Yes | 199 | 55 | 132 | 64 |
| HM61713 | NCT01588145 (139) | Yes | Yes | Yes | 93 | 17 | 27 | 66 |
| CO-1686 | NCT01526928 (140) | Yes | Yes | Yes | 88 | 58* | 55 | 58* |
pts, patients; EGFR, epidermal growth factor receptor; NR, not reported; ORR, objective response rate; E/G, erlotinib/gefitinib; A, afatinib; TKI, tyrosine kinase inhibitor; *, ORR was calculated from phase 2 which included only T790M+ pts.