The Role of Anti-EGFR Monoclonal Antibody in mCRC Maintenance Therapy

Abstract

Background: Epidermal growth factor receptor (EGFR) monoclonal antibodies (mAbs) combined with chemotherapy in patients with RAS (rat sarcoma viral oncogene homolog) wild-type metastatic colorectal cancer (mCRC) can alleviate and stabilize the disease, effectively prolong the progression-free survival (PFS) and overall survival (OS), and improve the overall response rate (ORR), which is the first-line treatment standard scheme for RAS wild-type mCRC currently. However, whether anti-EGFR mAb can be used for the maintenance treatment after the first-line treatment of mCRC remains controversial. We reviewed the recent studies on anti-EGFR mAb. The contents include five parts, introduction, anti-EGFR mAb in mCRC and its status in first-line therapy, establishment of the maintenance treatment pattern after the standard first-line treatment for mCRC, research progress of anti-EGFR mAb in mCRC maintenance therapy, and conclusion. More studies support the maintenance treatment of anti-EGFR mAb, but some researchers raise the problems about high cost and drug resistance. Despite lack of the maintenance evidence of anti-EGFR mAb, especially lack of large-scale phase III prospective clinical trials, with the emergence of new evidence and more accurate screening of treatment-dominant groups, maintenance therapy with anti-EGFR mAb monotherapy or anti-EGFR mAb combined with fluorouracil-based schemes after first-line chemotherapy combined with anti-EGFR mAb therapy might strive for more treatment opportunities, optimize treatment strategies and prolong treatment continuity, and finally, lead to more survival benefit for suitable patients.

Overcoming EGFR Resistance in Metastatic Colorectal Cancer Using Vitamin C: A Review

“…Combination chemotherapy has been regarded as the cornerstone for mCRC management [ 9 ]. Furthermore, anti-EGFR monoclonal antibodies (mAbs), such as Cetuximab, have proven to be an effective clinical therapy for mCRC patients with wild type KRAS tumors, and prolonged survival for 10–20% of patients [ 4 ]. One particular trial (CRYSTAL), revealed that the application of cetuximab and FOLFIRI can increase overall survival (OS) by 8.2 months and reduce the risk of progression by 15% in patients with KRAS wild type mCRC compared to FOLFIRI alone [ 10 ].…”

“…Specifically, in RAS, BRAF wild and MSS tumors, cytotoxic/cytostatic chemotherapy (5-FU), Vascular Endothelial Growth Factor Inhibitor (VEGF), and Multi-Kinase targeted agents, in addition to targeted monoclonal antibodies (against Epidermal Growth Factor Receptor (EGFR), have been widely used as the leading treatment modality against metastatic CRC (mCRC) [ 2 , 3 ]. Indeed, EGFR targeted therapy was found to increase overall survival by 10–20% in colorectal cancer [ 4 ]. However, resistance to this therapy was inevitable with the emergence of KRAS and BRAF mutations, driven by intrinsic and extrinsic mechanisms affecting both cellular pathways and tumor microenvironment, respectively.…”

Publication trends and hotspots of drug resistance in colorectal cancer during 2002-2021: A bibliometric and visualized analysis

“…Therefore, EGFR can regulate the activity of a variety of genes and participate in the occurrence, development and apoptosis and other physiological processes of tumors. Although anti-RGFR monoclonal antibody therapy represented by cetuximab and panitumumab has achieved expected clinical efficacy, most CRC patients develop varying degrees of drug resistance after 5-8 months of treatment, which significantly reduces the clinical benefit of anti-RGFR therapy ( 26 ). Since then, experts in this field have shifted their research focus to the molecular mechanism and prevention strategies of anti-EGFR drug resistance.…”

SEOM-GEMCAD-TTD clinical guidelines for the systemic treatment of metastatic colorectal cancer (2022)

“…After induction chemotherapy combined with bevacizumab, fluoropyrimidine maintenance with or without bevacizumab significantly improves PFS and reveals a trend toward prolonged OS and, hence, should be considered [I, B] [ 59 ]. Randomized phase II studies have shown an increase in efficacy with 5-fluorouracil with anti-EGFR MoAb maintenance versus anti-EGFR or 5-fluorouracil in monotherapy (II, B) [ 60 ].…”