Efficacy of anti-VEGF agents in the treatment of elderly hepatocellular carcinoma: a systematic review

PURPOSE: We aimed to investigate the role of anti-vascular endothelial growth factor (VEGF) agents, including tyrosine-kinase inhibitors or monoclonal anti-bodies, in the treatment of elderly hepatocellular carcinoma (HCC) patients. MATERIALS AND METHODS: Databases from PubMed, Web of Science and abstracts presented at ASCO meeting up to March 31, 2017 were searched to identify relevant studies. The endpoints were overall survival (OS) and progression-free survival (PFS). Data were examined using age cutoffs of 65 years. RESULTS: A total of 1,309 elderly (aged ≥ 65 years) HCC patients from seven trials were included for analysis. Our results demonstrated that the use of anti-VEGF agents MTAs in patients aged ≥ 65 years significantly improved PFS (HR 0.65, 95% CI: 0.55–0.76, p < 0.001) but not for OS (HR 0.87, 95% CI: 0.73–1.05, p = 0.15). Sub-group analysis according to treatment line showed that the use of anti-VEGF agents as second-line treatment significantly improved PFS (HR 0.55, 95% CI: 0.45–0.67, p < 0.001) and marginally improved OS (HR 0.83, 95% CI: 0.68–1.01, p = 0.061). Additionally, no survival benefits were observed in elderly HCC received first-line anti-VEGF treatments in terms of PFS (HR 0.87, 95% CI: 0.67–1.13, p = 0.29) and OS (HR 1.19, 95% CI: 0.74–1.36, p = 0.47). No publication bias was detected by Begg's and Egger's tests for OS. CONCLUSIONS: The findings of this study show that elderly HCC patients who relapsed after a first-line sorafenib treatment obtains a survival benefits from anti-VEGF agents rechallenge. Further studies are recommended to search for predictors of good responders in these patients received anti-VEGF agents.