Marco Miroddi is a PhD Student in Department of Clinical and Experimental Medicine at University of Messina. He is a Visiting Research Fellow in Department of Health Sciences at The University of York


Background: Cancer patients have a thrombophilic condition predisposing to thromboembolic events such as pulmonary embolism (PE), drug-exposure can increase this risk. Anti-Epidermal Growth Factor Receptor monoclonal antibodies (anti-EGFR MoAbs), Cetuximab and Panitumumab, are beneficial in the treatment of various malignancies, but are burdened by severe and life-threatening harms including PE. We conducted a systematic review and meta-analysis in order to determine the incidence and the risk of PE in cancer patients treated with Cetuximab and Panitumumab. Material & Methods: Medline, Embase, Web of Science, CENTRAL databases were searched for articles published until October 2014. Eligible studies were randomized phase II and III trials comparing anti-EGFR MoAbs containing regimens with the same regimens without anti-EGFR to treat cancer. Data on PE were extracted. Statistical analyses calculated the incidence of PE, RR and 95% confidence intervals (CIs) by using either random effects or fixed effect models with Mantel-Haenszel method. Subgroup analysis according kind of MoAb was performed. Also, we re-expressed RR in Number Needed to Treat to Harm (NNTH). We used funnel plot to assess potential publication bias. Results: Bibliographic search provided 6,777 records, after a selection process 6 articles were eligible. A total number of 6,773 patients were considered in our analysis. Patients receiving anti-EGFR MoAbs had a significantly increased risk of severe PE (RR:1.56; 95% CI 1.20 to 2.04) and a a incidence of 4.3% (95% CI 2.7 to 6.0%) vs. 2.7% (95% CI 1.6 to 3.8%). NNTH was 63 (95% CI 35 to 173). Statistical heterogeneity was irrelevant (I²=0%). Subgroups analyses revealed no differences between Cetuximab and Panitumumab. No publication bias was detected. Conclusions: The addition of anti-EGFR MoAbs increased the risk of PE by the 56%. Prevention, early recognition and appropriate clinical management of these severe and life-threatening AEs may optimize clinical outcomes reducing morbidity and mortality in cancer patients.