The efficacy and safety of bevacizumab plus erlotinib versus bevacizumab or erlotibib alone in the treatment of non-small cell lung cancer: A systematic review and meta-analysis

Abstract Objective To compare combination treatment with bevacizumab and erlotinib to bevacizumab or erlotinib monotherapy in NSCLC treatment. Methods Randomized controlled trials (RCTs), published in Pubmed, Web of Science, and Embase were systematically reviewed to evaluate the survival benefits and toxicity profile in NSCLC patients treated with bevacizumab and erlotinib. Main outcome measures included overall survival (OS), progression-free survival (PFS), overall response rate (ORR), and adverse events. Results were expressed as the hazard ratio (HR) with 95% confidence intervals (CIs), and risk ratio (RR) with 95%CIs. Pooled estimates were calculated by using a fixed-effects model or a randomized-effects model, according to the heterogeneity among studies. Results Five RCTs involving 1736 patients were included. The combination treatment of bevacizumab and erlotinib significantly improved the PFS and ORR as second-line treatment for NSCLC compared with bevacizumab or erlotinib alone. However, no significant difference in OS was observed between the combination group and monotherapy group. Subgroup analysis showed the highest PFS benefit in patients who were aged less than 65, or Asian/Pacific islanders, or Eastern Cooperative Oncology Group performance status 1, or stage IIIB or IV, or had never smoking. The incidence of grade 3/4 adverse events such as rash and diarrhea was higher in the bevacizuamb combination group than in the monotherapy group. Conclusions The addition of bevacizumab to erlotinib can significantly improve PFS and ORR in the second-line treatment of NSCLC, with an acceptable and manageable risk of rash and diarrhea, which confirmed the use of bevacizumab plus erlotinib in the second-line treatment of patients with NSCLC.