Table 1 The EGFR-independent mechanisms of EGFR-TKIs resistance and relevant clinical trials
From: EGFR-TKIs resistance via EGFR-independent signaling pathways
Mechanism | Frequency | Agents | Clinical Trials | Phase | Status | Reference |
|---|---|---|---|---|---|---|
Secondary RTKs | Â | |||||
MET amplification | 5%–22% | Crizotinib | NCT02737501 (NSCLC) NCT00932893 (NSCLC) | III III | Ongoing Has results | |
Tivantinib (ARQ197) | NCT01244191 (NSCLC) NCT01575522 (breast cancer) | III II | Completed Has results | |||
Cabozantinib (XL184) | NCT00596648 (NSCLC) NCT01834651 (prostate cancer) | I/II II | Completed Has results | |||
Capmatinib (INC280) | NCT01870726 (glioblastoma) NCT03040973 (solid tumors) | I/II IV | Completed Recruiting | |||
Onartuzumab (METMab) | NCT01456325 (NSCLC) | III | Completed | |||
LY2875358 | NCT01874938 (gastric cancer) | II | Completed | |||
MSC2156119J | NCT01014936 (solid tumors) | I | Has results | |||
HGF overexpression | 29%–61% | Rilotumumab (AMG102) | NCT01233687 (NSCLC) | I/II | Has results | |
ErbB2 amplification | 12%–37% | Afatinib | NCT02044380 (NSCLC) | III | Has results | |
Lapatinib | NCT00320385 (breast cancer) | III | Has results | |||
Trastuzumab | NCT01419197 (breast cancer) NCT00004883 (NSCLC) | III II | Has results Completed | |||
ErbB3 activation | 17%–52% | MM-121 | NCT00994123 (NSCLC) | I/II | Has results | |
IGF1R activation | 39–84% | Linsitinib (OSI-906) | NCT01533181 (SCLC) | II | Has results | |
Figitumumab | NCT00673049 (NSCLC) | III | Has results | |||
AXL activation | 20% | TP-0903 | NCT02729298 (solid tumors) | I | Recruiting | [70] |
FGFR activation | 10%–20% | BGJ398 | NCT01928459 (solid tumors) | I | Completed | |
Alternative downstream components | ||||||
PTEN loss | 9% | Ipatasertib | NCT02301988 (breast cancer) | II | Completed | [109] |
PIK3CA mutation | 5% | BYL719 | NCT01708161 (solid tumors) | I/II | Completed | [84] |
BRAF mutation | 1% | Dabrafenib | NCT01619774 (melanoma) | II | Has results | |