Risk of High-grade skin rash in cancer patients treated with cetuximab - An antibody against epidermal growth factor receptor: Systemic review and Meta-analysis

Background: Cetuximab, a chimeric antibody against epidermal growth factor receptor has emerged as an effective therapy for advanced colorectal cancer (CRC) and head-neck cancer. However, severe skin toxicity may limit its use. Its efficacy in the treatment of other cancers is also undergoing extensive investigation. We performed a systemic review and meta-analysis of published clinical trials to quantify the overall incidence and risk of severe skin rash. Methods: Databases Medline (OVID 1998 to July 2008), Web of Science, and abstracts presented at the American Society of Clinical Oncology conferences from 2004 through July 2008 were searched to identify relevant studies. Eligible studies include phase II and III clinical trials in which patients were treated with a single agent, i.e. cetuximab at 400 mg/m² as initial dose followed by 250 mg/m² weekly. Incidence, relative risk (RR), and 95% confidence intervals (CI) were calculated using a fixed-effects or random-effects model based on the heterogeneity of included studies. Results: A total of 2,037 patients with a variety of solid tumors from 16 trials were included for analysis. The overall incidence of all-grade skin rash was 88.2% (95% CI: 84.8-91.0%), with11.3% (95% CI: 8.8-14.3%) being high-grade (grade 3 or above). The overall incidence of all-grade acne-like skin rash was 81.6% (95% CI: 75.4-86.6%) with 6.5% (95% CI: 4.1-10.0%) being high-grade. Notably, patients with CRC exhibited a significantly higher incidence of high-grade skin rash (12.6%, 95% CI: 9.7-16.4%) than those with non-CRC (6.6%, 95% CI: 3.6-11.8%) with a risk ratio of 1.9 (95% CI: 1.0-3.6, p = 0.049). From randomized controlled studies, patients who received cetuximab had a significantly increased risk of developing high-grade skin rash in comparison with controls (RR 21.8, 95% CI: 6.9-68.8, p < 0.001). Conclusion: Cancer patients who received cetuximab have a substantial risk of developing high-grade skin rash. The risk may be particularly increased in patients with CRC. Further studies are strongly recommended for the prevention and treatment of high-grade skin rash.