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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  
MET amplification 5%–22% Crizotinib NCT02737501 (NSCLC) NCT00932893 (NSCLC) III III Ongoing Has results [21, 84, 102, 103]
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 [36, 104]
ErbB2 amplification 12%–37% Afatinib NCT02044380 (NSCLC) III Has results [45, 105]
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 [48, 106]
IGF1R activation 39–84% Linsitinib (OSI-906) NCT01533181 (SCLC) II Has results [64,65,66,67]
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 [107, 108]
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 [85, 110]