| Objectives: Epidermal growth factor receptor(EGFR) is a large family of receptor tyrosine kinases. EGFR is a protein receptor expressing on the cell membrane with a molecular weight of 170 k Da. The structural parts conclude out-cell domain binding with ligands, domain transferring cell membrane, intracellular domain containing the tyrosine kinase which can be activated, and the C-domain. It is reported that EGFR overexpress in many types of cancer, including breast, lung, esophagus, and head and neck. EGFR and its family members are the major contributors of a complex signaling cascade that modulates proliferation, anti-apoptosis, differentiation, adhesion, migration and survival of cancer cells. Anti-EGFR monoclonal antibodies(Mo Abs) cetuximab and panitumumab have emerged as an effective targeted therapy in the treatment of cancer patients, and these two kinds of drugs have been approved by the United States Food and Drug Administration(FDA). However, the overall incidence and risk of fatal adverse events(FAEs) associated with these agents is still unclear. FAEs are defined as deaths that are usually secondary to the use of the pharmaceutical agent. Patients with cancer may be at an increased risk because of the progressive nature of malignancy as well as the adverse events profiles of chemotherapeutic agents. Usually clinical trials have the disadvantages that lower number of subjects, big deviation, and difficulties to test the difference. Hence, we performed a Meta-analysis to evaluate the incidence and risk of EGFR-Mo Abs associated FAEs.Methods: Databases from Pub Med, Web of Science and abstracts presented at ASCO meeting up to May 31, 2013 were searched to identify relevant studies. Key words used for searching were “cetuximab”, “C-255”, “Erbitux”, “panitumumab”, “Vectibix”, “randomized”, and “cancer”. Eligible studies included prospective randomized controlled trials evaluating Mo Abs in cancer patients with adequate data on FAEs. The following information was extracted: author’s name, year of publication, trial phase, number of enrolled subjects, treatment arms, number of patients in treatment and control groups, median age, median treatment duration, FAEs, name and dosage of EGFR-Mo Abs and the dosing schedules used. Statistical analyses were conducted to calculate the summary incidence, odds ratio and 95% confidence intervals(CIs) by using either random effects or fixed effect models according to the heterogeneity of included studies.Results: A total of 14,776 patients with a variety of solid tumors from 21 clinical trials were included in our analysis. The overall incidence of Mo Abs associated FAEs was 1.7%(95%CI: 1.1-2.5%), and the incidence of cetuximab-related FAEs was higher than that of panitumumab(2.0% verses 0.9%). Compared with the controls, the use of Mo Abs was associated with a significantly increased risk of FAEs, with an OR of 1.37(95%CI: 1.04-1.81, P=0.024). Subgroup analysis based on EGFR-Mo Abs drugs, phase of trials and tumor types demonstrated a tendency to increase the risk of FAEs, but the risk did not increase in breast cancer, esophagus cancer and phase Ⅱ trials.Conclusions: With present evidence, the use of EGFR-Mo Abs is associated with an increased risk of FAEs in patients with advanced solid tumors. This study can guide the administration of targeted drug in clinic. |
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