Effectiveness and safety of bevacizumab for unresectable non-small-cell lung cancer: a meta-analysis.

BACKGROUND: Non-small-cell lung cancer (NSCLC) accounts for more than 85% of all cases of lung cancer. The 5-year survival of patients presenting with advanced stage NSCLC is less than 15%, indicating that additional treatment options are needed. Bevacizumab is a recombinant humanized version of the murine anti-human vascular endothelial growth factor (VEGF) monoclonal antibody with a high binding specificity for VEGF.
OBJECTIVE: The aim of this meta-analysis was to evaluate the effectiveness and safety of bevacizumab in patients with unresectable non-small-cell lung cancer (NSCLC) on the basis of evidence-based methodology.
METHODS: The electronic database PubMed was searched to identify randomized, controlled trials (RCTs) of bevacizumab for the treatment of unresectable NSCLC. Other databases such as the Cochrane Library Trials Register, the WHO Trial Registration, the National Cancer Institute, ClinicalTrials.gov, the European Organization for Research and Treatment of Cancer, the Southwest Oncology Group, the Eastern Cooperative Oncology Group, the European Society of Clinical Oncology and the American Society of Clinical Oncology were also searched. The meta-analysis was performed using Reviewer Manager Version 5.0 software provided by the Cochrane Collaboration. Outcome measures were overall survival rates, progression-free survival, tumour response rate, incidence of severe adverse events (SAEs) and treatment-related death.
RESULTS: Four eligible studies that included 2101 patients were found; in these studies, bevacizumab was administered to 1237 patients. Neither high-dose (15 mg/kg) nor low-dose (7.5 mg/kg) bevacizumab increased 1-year overall survival rates compared with patients not treated with bevacizumab. However, high-dose bevacizumab, rather than low-dose, increased 2-year overall survival rate (risk ratio [RR] = 1.24; 95% confidence interval [CI] 1.04, 1.49) and tumour response rate (RR = 1.69; 95% CI 1.21, 2.35) compared with patients not treated with bevacizumab. Progression-free survival was also significantly improved in both the low- (hazard ratio [HR] = 0.76; 95% CI 0.64, 0.90) and high-dose groups (HR = 0.73; 95% CI 0.65, 0.81). There was a clear and significant increase in the rate of treatment-related death in the high-dose group (RR = 2.07; 95% CI 1.19, 3.59) compared with patients not treated with bevacizumab. No significant differences were noted in the rate of treatment-related death in the low-dose group or in the incidences of SAE in the low- or high-dose groups compared with patients not treated with bevacizumab. Neutropenia was easily induced in both the low- and high-dose bevacizumab groups. Patients who received high-dose bevacizumab tended to experience hypertension, neutropenia, haemoptysis, rash and headache more frequently than patients not treated with bevacizumab.
CONCLUSIONS: Low-dose bevacizumab may significantly improve progression-free survival in patients with unresectable NSCLC, whereas high-dose bevacizumab may increase 2-year overall survival rates, prolong progression-free survival and improve tumour response rate but at the cost of higher treatment-related death. Larger well designed RCTs should be carried out in the future to clarify the role of bevacizumab in the treatment of NSCLC.