Abstract
Purpose: Sorafenib is the only approved drug in first-line treatment for hepatocellular carcinoma. Recently, the Phase III REFLECT trial proved lenvatinib not inferior to sorafenib, potentially establishing a new standard of care in this setting. The study showed that both have similar overall survivals, yet with longer time to progression for lenvatinib. Currently, the selection of one or other is not based on clinical or biological parameters for this reason we performed a network meta-analysis and we also analyzed the REFLECT trial and its implications in the current and future clinical practice. Materials and methods: We performed the meta-analysis according to the Prisma statement recommendations. HR was the measure of association for time to progression and overall survival. The pooled analysis of HR was performed using a random effect model, fixing a 5% error as index of statistical significance. Results: For HBV-positive patients, there was a clear trend in favor of lenvatinib over sorafenib (HR 0.82 95% credible interval [CrI] 0.60-1.15). For HCV-positive no differences between lenvatinib and sorafenib were observed (HR 0.91 95% CrI 0.41-2.01). The data showed that lenvatinib could be the best drug for HBV-positive patients in 59% of cases compared to only 1% of patients treated with sorafenib. Conclusion: The identification of clinical or biological markers that could predict response or resistance to treatments is needed to guide treatment decision. This network meta-analysis demonstrates that the etiology is a good candidate and this result should be validated in a specific trial.