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Abstract
BackgroundAnti-epidermal growth factor receptor (EGFR) monoclonal antibodies (MoAbs) cetuximab and panitumumab have emerged as an effective targeted therapy in the treatment of cancer patients, but the overall incidence and risk of fatal adverse events (FAEs) associated with these agents is still unclear. MethodsDatabases from PubMed, Web of Science and abstracts presented at ASCO meeting up to May 31, 2013 were searched to identify relevant studies. Eligible studies included prospective randomized controlled trials evaluating MoAbs in cancer patients with adequate data on FAEs. 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.ResultsA total of 14,776 patients with a variety of solid tumors from 21 clinical trials were included in our analysis. The overall incidence of MoAbs 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% versus 0.9%). Compared with the controls, the use of MoAbs 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-MoAbs 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. ConclusionsWith present evidence, the use of EGFR-MoAbs is associated with an increased risk of FAEs in patients with advanced solid tumors.
Highlights
Epidermal growth factor receptors (EGFR) are a large family of receptor tyrosine kinases which are overexpressed in many types of cancer[1], including breast[2], lung[3,4], esophageal[5], and head and neck[6]
Our search yielded 913 publications describing the use of cetuximab and panitumumab, and 21 randomized controlled trials (RCTs) were included in the meta-analysis
14,776 patients were investigated in these trials and they had a variety of cancers: colorectal cancer[24,25,26,27,28,29,30,31,32,33,34], non-small-cell lung cancer[35,36,37,38,39], head and neck cancer [40,41], esophagus carcinoma[42], pancreatic cancer[43] and breast cancer[44]
Summary
Epidermal growth factor receptors (EGFR) are a large family of receptor tyrosine kinases which are overexpressed in many types of cancer[1], including breast[2], lung[3,4], esophageal[5], and head and neck[6]. Erlotinib and gefitinib are oral small molecules designed to selectively inhibit the phosphorylation of EGFR intracellular kinase domain [10,11] These four drugs have shown clinical benefits in the treatment of many types of malignancy and have been approved for use in cancer therapy by the United States Food and Drug Administration (FDA)[10,11,12,13]. Anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (MoAbs) cetuximab and panitumumab have emerged as an effective targeted therapy in the treatment of cancer patients, but the overall incidence and risk of fatal adverse events (FAEs) associated with these agents is still unclear. Conclusions: With present evidence, the use of EGFR-MoAbs is associated with an increased risk of FAEs in patients with advanced solid tumors
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