Incidence and risk of severe infections associated with aflibercept in cancer patients: a systematic review and meta-analysis

Aims: Aflibercept is an engineered humanized vascular endothelial growth factor (VEGF)-targeted agent. Severe infections are serious adverse event associated with aflibercept. However, the contribution of aflibercept to infection is still unknown. We thus conducted this meta-analysis to investigate the overall incidence and risk of developing severe infections in cancer patients treated with aflibercept.

Methods: Electronic databases including PubMed, Embase and abstracts presented at American Society of Clinical Oncology (ASCO) and European Society of Medical Oncology (ESMO) meeting were searched. Eligible studies were phase II and III prospective clinical trials of aflibercept in cancer patients with toxicity profile on infections. Summary incidences, relative risk (RR), odds ratio (OR) and 95% confidence intervals (95% CIs) were calculated by using either random effects or fixed effect models according to the heterogeneity of included studies.

Results: A total of 4310 patients with a variety of solid tumours from 10 prospective clinical trials were included in the meta-analysis. The incidence of high grade infections associated with aflibercept was 7.3% (95% CI 4.3, 12.0%), with a mortality of 2.2% (95% CI 1.5, 3.1%). In addition, patients treated with aflibercept had a significantly increased risk of developing high grade (RR 1.87, 95% CI 1.52, 2.30; P < 0.001) and fatal (OR 2.16, 95% CI 1.14, 4.11; P = 0.018) infections. No evidence of publication bias was observed. Furthermore, the risk of infections with aflibercept was substantially higher than bevacizumab.

Conclusions: Aflibercept is associated with a significant increased risk of developing severe infections in patients with solid tumours. Frequent clinical monitoring and appropriate management for infections should be emphasized during aflibercept treatment.