Angiogenesis inhibitors rechallenge in patients with advanced non-small-cell lung cancer: a pooled analysis of randomized controlled trials

PURPOSE: Data on the role of angiogenesis inhibitors (AIs) rechallenge in the treatment of advanced non-small-cell lung cancer (NSCLC) patients who previously received bevacizumab remain limited. We aim to investigate the efficacy of AIs in the treatment of advanced NSCLC in this setting. METHODS: Studies from PubMed, Web of Science, and abstracts presented at American Society of Clinical Oncology meeting up to December 1, 2014 were searched to identify relevant studies. Eligible studies included prospective randomized controlled trials evaluating AIs in advanced NSCLC, with survival data on patients who previously received bevacizumab. The end points were overall survival and progression-free survival. Statistical analyses were conducted by using either random effects or fixed effect models according to the heterogeneity of included studies. RESULTS: A total of 452 patients with advanced NSCLC who previously received bevacizumab were identified for analysis. The meta-analysis results demonstrated that AI rechallenge significantly improved progression-free survival (hazard ratio: 0.72, 95% confidence interval: 0.58–0.89, P=0.002) when compared to non-AI containing regimens. Additionally, a nonsignificant improvement in overall survival was also observed in advanced NSCLC in this setting (hazard ratio: 0.82, 95% confidence interval: 0.65–1.03, P=0.087). Similar results were also observed in subgroup analysis according to treatment regimens. CONCLUSION: The findings of this study suggest that NSCLC patients who relapsed after a first-line bevacizumab-containing chemotherapy obtain improved clinical benefits from AI rechallenge. Prospective clinical trials investigating the role of AI rechallenge in this setting are recommended.