Modern strategy for treatment of metastatic colorectal cancer as key to increasing life expectancy of patients with metastatic colorectal cancer without mutations in RAS genes

Abstract

The review is devoted to the place of cetuximab in the treatment of metastatic colorectal cancer (mCRC) without mutations in the RAS (RAS wt) and BRAF (BRAF wt) genes, depending on the goals of therapy, as well as to the analysis of the inflence of various factors, including the localization of the primary tumor, on the effectiveness of treatment. Randomized clinical trials and meta-analyses conducted on their basis allow us to conclude that cetuximab in combination with an infusion doublet or triplet provides the maximum frequency of deep and early objective responses, regardless of the location of the primary tumor. The drug is superior in this parameter to both a single chemotherapy (CT) and a combination of CT with bevacizumab which is important in terms of achieving resectability in patients with potentially resectable metastases. For patients with left-sided localization of the primary tumor and RAS wt, cetuximab, prescribed in the 1st line, provides a reliable and clinically signifiant increase in life expectancy. Postponing the start of its use until 2–4 cycles of CT (until the result of a molecular genetic study is obtained) does not negatively affect the effectiveness of the 1st line of therapy for mCRC RAS wt, and with left-sided localization of the primary tumor, CT with delayed cetuximab exceeds the usage of CT with bevacizumab from the fist cycle for ORR, OS and PFS. The optimal duration of induction chemo-targeted therapy is 3–4 months (6–8 courses), after which it is advisable to switch to maintenance treatment with one cetuximab. The new mode of administration of cetuximab once every 2 weeks at a dosage of 500 mg/m 2 IV provides maximum convenience of its use.