Incidence and risk of severe infections associated with anti-epidermal growth factor receptor monoclonal antibodies in cancer patients: a systematic review and meta-analysis

Abstract

Background: Anti-epidermal growth factor receptor (EGFR)-monoclonal antibodies (MoAbs) have been widely used in a variety of malignancies. Severe infections (≥grade 3) are potentially life-threatening adverse events with these drugs. However, the contribution of anti-EGFR MoAbs to infections is still unknown. We performed this meta-analysis to determine the overall incidence and risk of severe infections in cancer patients treated with these drugs. Methods: The databases of PubMed and abstracts presented at oncology conferences and published in the proceedings were searched for relevant studies from January 2000 to May 2014. Summary incidences, relative risks (RRs) and 95% confidence intervals (CIs) were calculated by using either random effects or fixed effect models according to the heterogeneity of included studies.

Incidence and risk of infections associated with EGFR-TKIs in advanced non-small-cell lung cancer: a systematic review and meta-analysis of randomized controlled trials

“…Rafailidis et al [42] conducted the first systematic review in 2007 and demonstrated that there was an increased risk of developing monoclonal antibodies related severe infections but not for fatal adverse events. In consistent with previous results, two later meta-analyses also showed that EGFR-monoclonal antibodies significantly increased the risk of developing severe infections but not for fatal adverse events [16, 43]. Recently, Qi et al performed another meta-analysis and showed that there was an increased risk of developing all-grade (RR 1.45, p < 0.001) and high-grade (RR 1.59, p < 0.001) infectious events in cancer patients treated with bevacizumab [44].…”

“…Infections have been reported with anti-EGFR agents. In 2014, Qi et al performed a meta-analysis and found a significantly increased risk of severe infectious events associated with the use of anti-EGFR mono-clonal antibodies cetuximab and panitumumab in cancer patients (RR 1.34, p = 0.003) [16]. However, whether EGFR-TKIs increase the risk of infections in NSCLC remains unknown.…”

System-Wide Mapping of Activated Circuitry in Experimental Systemic Inflammatory Response Syndrome

“…The widespread availability and clinical use of EGFR inhibitors as anti-neoplastic therapies provides future opportunities to explore the functional role of this SIRS-associated network hub in severe sepsis through direct pharmacologic targeting. Interestingly, inhibition of the EGF-EGFR axis using anti-EGFR monoclonal antibodies is associated with increased risk of severe infections in cancer patients (31), further implicating this pathway as a key regulator of host response to sepsis. Furthermore, several other network nodes identified from our analysis are druggable sites, further supporting the utility of our approach in systematically identifying new therapeutic targets in MODS (please see Supplementary Table S2).…”

Treatment-related severe and fatal adverse events with molecular targeted agents in the treatment of advanced gastric cancer: a meta-analysis

“…Another meta-analysis also demonstrated that the use of anti-EGFR MoAbs significantly increased the risk of developing severe infections (RR: 1.34, 95% CI: 1.10–1.62, P =0.003) in cancer patients. More importantly, the use of anti-EGFR MoAbs significantly increased the risk of severe sepsis in cancer patients (RR: 4.30, 95% CI: 1.80–10.27, P =0.001) 37. On the basis of these findings, clinicians should pay more attention to severe infections to reduce the risk of FAEs in advanced gastric patients.…”