Centre Hospitalier Régional Universitaire (CHU) de Montpellier, Université Montpellier, Département d’Oncologie médicale, 80 avenue Augustin Fliche, 34295 Montpellier
Université Montpellier, Institut du Cancer de Montpellier (ICM), Département d’Oncologie Médicale
Over the past decade, sorafenib has been the only systemic agent with proven clinical efficacy for patients with unresectable hepatocellular carcinoma (HCC). Recently, lenvatinib was shown to be non inferior to sorafenib, while regorafenib, cabozantinib, and ramucirumab were shown to be superior to placebo in patients failing sorafenib. Last year, trials of immune checkpoint inhibitors (PD-1, PD-L1 ou CTLA-4) reported encouraging efficacy signals but are not yet approved (in part due to the lack of predictive biomarkers for immunotherapy response). Indeed, apart from alpha-fetoprotein, which is used to select patients for ramucirumab, no biomarkers are available to identify patients that may respond to a specific treatment. Different synergisms have been postulated based on the potential interplay between antiangiogenic drugs and immunotherapy, with several clinical trials currently testing this hypothesis. Thus, encouraging preliminary results of phase I, III studies of bevacizumab plus atézolizumab will etablish antiangiogenics and immune checkpoint inhibitors combination in the front-line setting. In this review, we discuss the most recent data on novel strategies and targets, as well as looking ahead to the future role of molecular therapies in the treatment of patients with advanced HCC.