Pemetrexed/Erlotinib as a Salvage Treatment in Patients with High EGFR-Expressing Metastatic Colorectal Cancer Following Failure of Standard Chemotherapy: A Phase II Single-Arm Prospective Study.
Population pharmacokinetics and covariate analysis of Sym004, an antibody mixture against the epidermal growth factor receptor, in subjects with metastatic colorectal cancer and other solid tumors.
The development of monoclonal antibodies (mAbs) cetuximab and panitumumab, which target the transmembrane protein epidermal growth factor receptor (EGFR), mark a major step forward in the treatment of metastatic colorectal cancer (mCRC).
Patients with <i>HER2</i>-amplified/overexpressed metastatic colorectal cancer (mCRC) harbor a driver actionable molecular alteration that has been shown in preclinical models to hamper efficacy of the anti-epidermal growth factor receptor (EGFR) targeted therapies.
Cetuximab and panitumumab are two distinct monoclonal antibodies (mAbs) targeting the epidermal growth factor receptor (EGFR), and both are widely used in combination with chemotherapy or as monotherapy to treat patients with <i>RAS</i> wild-type metastatic colorectal cancer.
<b>:</b> Targeting the epidermal growth factor receptor (EGFR) either alone or in combination with chemotherapy in patients with RAS wild type metastatic colorectal cancer (mCRC) has revolutionized the treatment of CRC, but with less results than initially envisaged.
Patients with metastatic colorectal cancer (mCRC) who fail treatment with standard therapies, including chemotherapy and monoclonal antibodies targeting vascular endothelial growth factor or epidermal growth factor receptor, have few treatment options.
This review describes the clinical and biological evolution and development of EGFR targeted therapies in mCRC, the challenges in the presence of molecular complexities, the role of cell free (cf)-DNA and future strategies that could lead to further optimal discovery of clinically meaningful biomarkers and application of precision medicine.
Taken together, the superior antitumor efficacy of GC1118 alone or in combination with PI3K/mTOR/AKT inhibitors shows great therapeutic potential for the treatment of <i>KRAS</i>-mutant mCRC with elevated ratios of high- to low-affinity EGFR ligands and PI3K-AKT pathway activation.
Treatments in this setting can include regorafenib (an oral multikinase inhibitor), trifluridine/tipiracil hydrochloride (TAS-102), antibodies that target epidermal growth factor receptor for patients with RAS wild-type tumors (if no prior exposure), and, where approved, anti-programmed cell death protein 1 inhibitors for patients with microsatellite instability-high mCRC.
<b>Expert commentary:</b> Fruquintinib was approved for patients with metastatic colorectal cancer (RAS wild type) who have previously received fluorouracil, oxaliplatin, and irinotecan-based chemotherapy and who have received or are not suitable for anti- VEGF therapy and anti- EGFR therapy.
Therefore, we performed this review to summarize the available data regarding the optimal sequential treatment of anti-EGFR and -VEGF mAb for RAS or KRAS WT mCRC and discuss the potential mechanisms that may explain this phenomenon.
KRAS and NRAS mutations are identified resistance mutations to anti-epidermal growth factor receptor monoclonal antibodies in patients with metastatic colorectal cancer.
The present study focuses on the involvement of EGFR positive and negative feedback genes in the establishment of cetuximab (CTX) resistance in metastatic Colorectal Cancer (CRC) patients.
Monoclonal antibodies targeting epidermal growth factor receptor (EGFR) or vascular endothelial growth factor (VEGF) have demonstrated efficacy with chemotherapy (CT) as second line treatment for metastatic colorectal cancer (mCRC).
Combining tivantinib, an inhibitor of the MET receptor tyrosine kinase, and cetuximab may be effective in patients with epidermal growth factor receptor-resistant MET-high mCRC.