Comparison of efficacy and safety of bevacizumab biosimilar and original bevacizumab in non-squamous non-small cell lung cancer: a systematic review and meta-analysis

BACKGROUND: Bevacizumab (Avastin(®)), a monoclonal antibody targeting vascular endothelial growth factor (VEGF)-A, is widely used in treating a variety of malignant tumors. Several biosimilars of bevacizumab have been developed and marketed with the expiration of bevacizumab’s patent. The objective of this study was to collate available data from head-to-head randomized controlled trials (RCTs) and evaluate the efficacy and safety of biosimilar bevacizumab compared with the bevacizumab (Avastin(®)) in patients with non-squamous non-small cell lung cancer (NSCLC). METHODS: Literature search of Web of Science, PubMed, Cochrane Library, EMBASE, and ClinicalTrials.gov was performed from inception until October 15, 2021. The efficacy outcome indicators were objective response rate (ORR), progression-free survival (PFS) and overall survival (OS). The occurrence of adverse events (AEs) was evaluated for safety outcome. RESULTS: Ten RCTs recruiting 6,416 patients with non-squamous NSCLC were included. All RCTs studies included the biosimilar bevacizumab group as the experimental group and the original bevacizumab group as the control group. The patients in the experimental group and control group received the same dose and duration of chemotherapy combined with carboplatin and paclitaxel. The results of meta-analysis showed that there were no significant differences in ORR [risk ratio (RR): 0.97, 95% confidence interval (95% CI): 0.93–1.02. P=0.841, I(2)=0], PFS (RR: 1.04, 95% CI: 0.98–1.10, P=0.235, I(2)=0) and OS (RR: 1.05, 95% CI: 1.00–1.10, P=0.692, I(2)=0) between the biomarker and original groups. The P values of ORR, PFS and OS were 0.533, 0.970 and 0.916 respectively as shown by Egger's test, suggesting that there was no publication bias. Subgroup analysis showed no significant differences in ORR, PFS, and OS between the Chinese and multicenter trials. The pooled incidence rate of AEs between two groups was similar, and there was also no significant difference between the two groups. DISCUSSION: This is the first study to independently report biosimilar bevacizumab in a meta-analysis on NSCLC treatment. The results showed that biosimilar bevacizumab had similar efficacy and safety compared with the original bevacizumab. TRIAL REGISTRATION: PROSPERO registration No. CRD42021276991.