| Background In recent years, numerous large clinical randomized controlled trials of bevacizumab in combination with the traditional two medicine chemotherapy or with other targeted drug were launched in the domestic and overseas for treating recurrence or metastasis of non small cell lung cancer (NSCLC). However, the application dosage, safety, efficacy and the suitable crowd of various combination regimens remains controversial, and the optimal chemotherapy regimens for treating non-squamous non small cell lung cancer (non-squamous NSCLC) is unclear.Purposes In this study, we sought to conduct a systematic review and meta-analysis to primarily estimate the safety, efficacy and the suitable crowd of various combination regimens and compare/select the optimal treatment regimen for non-squamous NSCLC chemotherapy.Methods The Cochrane Library database, PubMed/MEDLINE, Web of Science, and Chinese biomedical literature database (CBM), Chinese National Knowledge Infrastructure (CNKI), Weip database (VIP), Wanfang database were searched for collecting eligible randomized controlled trials (RCT) comparing the combination of bevacizumab with chemotherapy regimens versus chemotherapy alone. Main indicators include objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), treatment related mortality (TRM) and toxic effects, etc. Hazard ratios (HRs) and 95% confidence intervals (CIs) from individual study were pooled through a fixed- or random-effect model, heterogeneity and publication bias analyses were also performed by STATA 12.0.Results 10 eligible trials covering 3540 patients (2014 for bevacizumab and 1526 for controls) were included in the meta-analysis. Meta analysis show that low dose (7.5 mg/kg) and high dose (15mg/kg) of bevacizumab in combination with chemotherapy could improve the objective response rate (ORR) of the tumor (RR=1.605,95%CI: 1.280-2.013, P< 0.001; RR=1.877 95%CI:1.627-2.164, F< 0.001, respectively). Low dose (7.5mg/kg) of bevacizumab in combination with chemotherapy compared with pure chemotherapy for NSCLC as first-line drugs could decrease the risk of disease progression (HR=0.792,95%CI:0.671-0.935, P=0.006), but the reduction of disease death risk (HR=0.905,95%CI:0.776-1.070, P=0.243) was not observed. Regarding high dose (15mg/kg) of bevacizumab in combination with chemotherapy could significantly reduce the disease progression risk (HR=0.647,95%CI:0.596-0.704, P< 0.001) for NSCLC, and the death diseases risk (HR=0.920,95%CI:0.845-1.002, P= 0.057) was also not decreased; First-line administration could reduce the disease progression risk (HR=0.609,95%CI:0.505-0.735, P< 0.001), but the lower risk of disease death (HR=0.921,95%CI:0.835-1.016, P=0.102) was not observed; As second-line treatment, the disease progression risk (HR= 0.624,95%CI:0.524-0.742, P< 0.001) was decreased and disease risk of death (HR=0.936,95%CI:0.780-1.124, P=0.479) was not benefited. Subgroup analysis indicating that bevacizumab combination paclitaxel-carboplatin (Bev+PC) chemotherapy regimens as first-line treatment can statistically significant improve PFS (HR=0.577,95%CI:0.451-0.739, P< 0.001) and prolong OS (HR=0.820,95%CI:0.715-0.941, P=0.005) for non-squamous NSCLC. Additional, high dose (15mg/kg) of bevacizumab in combination with chemotherapy significantly increased treatment-related deaths (RR=2.025,95%CI:1.190-3.455, P= 0.009) and the incidence of related toxic effects such as hemorrhage, hypertension, and proteinuria etc.Conclusion Bevacizumab (7.5mg/kg and 15mg/kg) combined with chemotherapy was found to significantly improve ORR, PFS in patients with NSCLC as first-and second-line administration, only bevacizumab combined with paclitaxel plus carboplatin (Bev+PC) chemotherapy regimens as first-line treatment can significantly improve PFS and prolong OS in patients with non-squamous NSCLC. |
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