Risk of Serious Neutropenic Events in Cancer Patients Treated with Bevacizumab: A Meta-analysis

Bevacizumab has been approved for use in combination with chemotherapy to treat many types of cancerbut associated neutropenic events, including febrile neutropenia, have been reported. To estimate the incidenceand relative risk of neutropenic events in cancer patients treated with bevacizumab combination therapy, wesearched PubMed, EMBASE, and Web of Science literature databases, as well as abstracts presented at theAmerican Society of Clinical Oncology conferences, to identify relevant studies published from January 1966 toDecember 2011. Studies that compared bevacizumab plus chemotherapy or biological therapy with chemotherapyor biological therapy alone, and that had adequate safety data profiles, were selected for analysis. Statisticalanalyses were conducted to calculate the summary incidence rates, relative risks (RRs), and 95% confidenceintervals (CIs) using fixed- or random-effects models. A total of 22 clinical trials involving 15,056 patients wereincluded in the analysis. The summary incidences of high-grade neutropenia (HGN) and high-grade febrileneutropenia (HGFN) in patients receiving bevacizumab was 27.3% (95% CI: 26.4%-28.3%) and 3.91% (95%CI: 3.51%-4.37%), respectively. The risks of HGN (RR=1.10; 95% CI: 1.02-1.19; P=0.02) and HGFN (RR=1.31;95% CI: 1.08–1.59; P=0.005) were significantly increased in bevacizumab-treated patients, compared to those whodid not receive bevacizumab. The RR of bevacizumab-associated HGN, but not HGFN, varied significantly withtumor types (P=0.005). The increased risk of bevacizumab-associated neutropenic events was dose-dependent,as the RR was greater at a dose of 5 mg/kg/week than at 2.5 mg/kg/week. Our findings suggest that bevacizumabaddition to cancer therapy significantly increases the risk of serious neutropenic events, and this risk may bedose-dependent.