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Most of patients with hepatocellular carcinoma (HCC), are diagnosed at an advanced-stage explaining the poor prognosis of this cancer with a median survival without treatment around 8 months (1-3). Currently, two systemic multi-kinase inhibitors with anti-proliferative and antiangiogenic effects are available as first line treatments in advanced HCC. The first one, Sorafenib, was the only available systemic treatment available during one decade and was associated with an improvement of overall survival of around 3 months compared to placebo (4,5). The second one, lenvatinib, showed a similar median overall survival compared to Sorafenib in a non-inferiority phase-3 trial (6). No second line was available during several years due to toxicity or absence of efficacy of the different drugs tested in multicentric phase 3 randomized controlled trials.