Therapy | Target | Agents | Setting | Species | Subpopulation | Treatment regimen | Efficiency | Reference |
---|---|---|---|---|---|---|---|---|
New anti-EGFR mAbs | EGFR S468R | necitumumab | Phase II | mCRC | Unselected | Necitumumab plus mFOLFOX6 | mPFS:10.0m; mOS:22.5m | [21] |
EGFR ECD | Sym004 | Phase I | mCRC | KRAS WT | Sym004 or investigator’s choice | mOS: 12.8m VS 7.3m | [22] | |
EGFR-TK | Erlotinib | Phase II | mCRC | KRAS WT | Erlotinib+ cetuximab | ORR:42%; mPFS:5.6m | [23] | |
RAS inhibitors | RAS | Dasatinib | Phase IB/II | mCRC | KRAS mutation | Dasatinib + FOLFOX +cetuximab | Not reached | [24] |
 | BRAF | Vemurafenib | Phase IB | mCRC | BRAF V600E mutation | Vemurafenib + Irinotecan + cetuximab | ORR:35%; mPFS:7.7m | [25] |
RAF inhibitors | Phase II | mCRC | Unselected | Vemurafenib+ cetuximab VS cetuximab | ORR:0 VS 4%; mPFS3.7 VS 4.5m; mOS:7.1m VS 9.3m | [26] | ||
 | Encorafenib | Phase III | mCRC | BRAF V600E mutation | Encorafenib + binimetinib + cetuximab VS cetuximab chemotherapy | ORR: 26% VS 2%, mOS: 9.0m VS 5.4m | ||
MEK inhibitors | MEK | Binimetinib | Phase III | mCRC | BRAF V600E mutation | Encorafenib + binimetinib + cetuximab VS cetuximab chemotherapy | ORR: 26% VS 2%, mOS: 9.0m VS 5.4m | [28] |
Selumetinib | Phase I | mCRC | KRAS mutation | Selumetinib + cetuximab | Not reached | |||
ERBB2 inhibitors | ERBB2 | Neratinib | Phase II | mCRC | KRAS, NRAS, BRAF, PIK3CA WT | Neratinib + cetuximab | Not reached | [31] |
PI3K inhibitors | PI3K | PX-866 | Phase II | mCRC | KRAS WT | PX-866 + cetuximab VS cetuximab | mPFS:59d VS 104d; mOS:266d VS 333d | [32] |
MET inhibitors | MET | Tivantinib | Phase II | mCRC | KRAS mutation | Tivantinib + cetuximab | ORR: 9.8%, mPFS: 2.6m,mOS:9.2m | [33] |
Capmatinib | Phase II | mCRC | MET amplification | Capmatinib + gefitinib | ORR: 47% | [34] | ||
IGF-1R inhibitors | IGF-1R | Dalotuzumab | Phase II/III | mCRC | KRAS WT | Dalotuzumab + Irinotecan + cetuximab VS placebo + Irinotecan + cetuximab | mPFS: 5.4m VS 5.6m;mOS:11.6 VS 14.0m | [35] |
IMC-A12 | Phase II | mCRC | Unselected | IMC-A12 + cetuximab VS IMC-A12 | Non response | [36] | ||
Metabolic regulators | SGLT2 | Dapagliflozin | Case report | mCRC | SGLT2+ | Dapagliflozin + cetuximab | CEA dropped and tumor regression | [37] |
Immune checkpoint inhibitors | PD-L1 | Avelumab | Phase II | mCRC | RAS WT | Avelumab + cetuximab | mPFS:3.6m; mOS:11.6m | [38] |
Antiangiogenic agents | VEGFR | Regorafenib | Phase I | mCRC | At least 4-line treatment | Regorafenib + cetuximab | PR:1/17; SD: 7/17 | [39] |