Objectives: Bevacizumab and erlotinib exhibit beneficial effects in the treatment of non-small-cell lung cancer (NSCLC). However, the efficacy of bevacizumab in combination with erlotinib remains controversial. Therefore, we conducted a meta-analysis to compare combination treatment with bevacizumab and erlotinib to bevacizumab or erlotinib monotherapy in the treatment of NSCLC.
Methods: Randomized controlled trials (RCTs) published in PubMed, Web of Science, and Embase were systematically reviewed. The main outcome measures included overall survival (OS), progression-free survival (PFS), the overall response rate (ORR), and adverse events. Results were expressed as hazard ratios (HRs) or risk ratios (RRs) with 95% confidence intervals (CIs).
Results: Five RCTs involving a total of 1736 patients met the inclusion criteria, and these studies were included in this meta-analysis. The combination of bevacizumab and erlotinib significantly improved PFS (HR=0.63, 95%CI: 0.53–0.75; P=0.000) and the ORR (RR=1.91, 95%CI: 1.19–3.06; P=0.007) in the second-line treatment of NSCLC compared with bevacizumab or erlotinib alone. However, no significant difference in OS was observed between the combination and monotherapy groups (HR=0.96, 95%CI: 0.83–1.11; P=0.573). Subgroup analysis revealed that the greatest PFS benefit was associated with an age of less than 65years(HR=0.74, 95%CI: 0.57–0.96; P=0.026), Asian/Pacific Islander ethnicity (HR=0.23, 95%CI: 0.10–0.54; P=0.001), Eastern Cooperative Oncology Group performance status(ECOG PS) 1 (HR=0.82, 95%CI: 0.68–0.98; P=0.033), stage IIIB or IV disease(HR=0.68, 95%CI: 0.57–0.82; P=0.000), and no history of smoking (HR=0.48, 95%CI: 0.32–0.71; P=0.000). The incidence of grade 3/4 adverse events such as rash and diarrhea was higher in the combination group than in the monotherapy group.
Conclusion: The addition of bevacizumab to erlotinib can significantly improve PFS and the ORR in the second-line treatment of NSCLC with an acceptable and manageable risk of rash and diarrhea. Further well-conducted, large-scale trials are needed to validate these findings.
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