Treatments involving monoclonal antibodies used in patients with metastatic colorectal cancer as a strategy to decrease drug resistance caused by mutations in the KRAS/NRAS genes. Protocol for systematic review

Colorectal cancer (CRC) is the most common type of cancer that occurs in the digestive system. In recent years, the incidence of this type of cancer has increased significantly. Currently, most patients with this type of cancer are prescribed conventional cytotoxic drugs; these drugs are the main chemotherapeutic agents against cancer, however, they have serious side effects. For the treatment of CRC, the most common chemotherapeutic drugs are monoclonal antibodies (mAbs), such as Cetuximab, Panitumumab and Bevacizumab, which act by blocking epidermal growth factor signaling. The disadvantage is that these mAbs are usually very expensive, in addition, several patients with CRC show drug resistance when treated with these drugs [1]. Metastasis is the main cause of death in CRC patients. In recent years, the application of chemotherapy and molecular targeted therapies, including mAbs against epidermal growth factor receptor (EGFR) and mAbs against vascular endothelial growth factor, has improved the prognosis of patients with metastatic colorectal cancer (mCRC) [2]. As a first-line treatment, cetuximab in combination with chemotherapy has been recommended, however, drug resistance to cetuximab exists widely. Clinical studies show that cetuximab is effective for only about 10 % of patients with mCRC. Many efforts have been made to find biomarkers or drivers of cetuximab drug resistance in order to increase its efficacy and improve the treatment of mCRC. Drug resistance to cetuximab can be classified into acquired resistance, which often occurs 3 to 12 months after effective response to treatment. Mutations in the KRAS and NRAS genes are the most common causes of acquired resistance to cetuximab [2]. In 2019, E. Elez, et al. performed a phase 2 study where panitumumab plus irinotecan is used to improve EGFR-targeted therapy, this because the first treatment with irinotecan in the 46 patients with KRAS exon-2 wild-type had failed because they presented resistance to the drug. In this article, we aimed to evaluate the safety, overall survival (OS) and progression-free survival (PFS) of the treatment applied to the patients. [3]. Mutations in KRAS/NRAS are important biomarkers in mCRC that predict lack of benefit from epidermal growth factor receptor antibodies and occur in approximately 60% of mCRC cases. Identification of these alterations is important not only to avoid the potential toxicity of ineffective therapy, but RAS mutations may also predict a worse outcome after anti-EGFR treatment. Because of the strength of RAS mutations as a predictive biomarker, testing for these alterations has become essential prior to treatment with cetuximab or panitumumab [4]. Molecular profiling of colorectal tumors has better defined patients who may benefit from targeted therapy. In patients with KRAS wild-type (WT) tumors, treatment with cetuximab compared with supportive care significantly improved median OS 9.5 months vs. 4.8 months; hazard ratio 0.55; 95 % confidence interval (CI) 0.41 to 0.74; p