Erlotinib plus bevacizumab versus erlotinib alone in patients with EGFR-positive advanced non-small-cell lung cancer: a systematic review and meta-analysis of randomised controlled trials

OBJECTIVES: Combination treatment with erlotinib plus bevacizumab has the potential to become a standard treatment regimen for patients with epidermal growth factor receptor mutation-positive (EGFRm(+)) advanced non-small cell lung cancer (NSCLC). This study aimed to investigate the efficacy and safety of erlotinib plus bevacizumab in patients with EGFRm(+) advanced NSCLC. DESIGN: Systematic review and meta-analysis. DATA SOURCES: The PubMed, Embase, Web of Science and Cochrane Library databases were searched, from inception to 15 January 2022. ELIGIBILITY CRITERIA: We included randomised controlled trials (RCTs), reported in English, assessing the efficacy of erlotinib plus bevacizumab versus erlotinib monotherapy in patients with EGFRm(+) advanced NSCLC. DATA EXTRACTION AND SYNTHESIS: The main objective was to assess overall survival (OS), progression-free survival (PFS), objective response rate (ORR) and adverse events (AEs). Two independent reviewers extracted data and assessed the risk of bias. A random-effects model was used where there was evidence for homogeneous effects. RESULTS: Four RCTs (reported across six publications) were included in the meta-analysis, with a total of 775 patients included in the pooled analyses of PFS, OS and ORR (387 in the erlotinib plus bevacizumab intervention group and 388 in the erlotinib group). Compared with the erlotinib alone group, the erlotinib plus bevacizumab group achieved a significantly prolonged PFS (HR: 0.59; 95% CI 0.49 to 0.72; p<0.00001; I(2)=0%), but OS (HR: 0.95; 95% CI 0.78 to 1.15; p=0.59; I(2)=0%) and ORR (OR: 1.25; 95% CI 0.89 to 1.74; p=0.19; I(2)=0%) were not significantly prolonged. A total of 776 cases were used for a pooled analysis of AEs. Regarding AEs, combined treatment significantly increased the incidence of diarrhoea (51% vs 43%, 95% CI 1.03 to 1.38; p=0.006), haemorrhagic events (41% vs 20%, 95% CI 1.12 to 6.31; p=0.03), proteinuria (25% vs 3%, 95% CI 4.86 to 17.66; p<0.0001) and hypertension (40% vs 8%, 95% CI 3.66 to 7.88; p<0.0001). CONCLUSIONS: Erlotinib plus bevacizumab for the treatment of patients with EGFRm(+) advanced NSCLC was associated with significantly prolonged PFS compared with erlotinib alone, but the combination did not prolong OS.