The COSMIC-312 study: will it shape future combination therapies for advanced hepatocellular carcinoma?
Mené sur 432 patients atteints d'un carcinome hépatocellulaire de stade avancé, cet essai de phase III compare l'efficacité, du point de vue de la survie sans progression et de la survie globale, et la toxicité d'un traitement de première ligne comportant le cabozantinib en combinaison avec l'atézolizumab et d'un traitement par sorafénib
Thomas Yau and colleagues' final analysis of the COSMIC-312 trial, a phase 3 randomised controlled trial aiming to assess the efficacy of a TKI-based immunotherapy doublet as first-line systemic treatment, in The Lancet Gastroenterology & Hepatology, adds to our knowledge about the use tyrosine kinase inhibitor (TKI) plus immune checkpoint inhibitor (ICI) combinations for treatment of advanced hepatocellular carcinoma. Although the role of ICI plus the VEGF-targeted agent bevacizumab or the combination of two ICIs is well established in advanced hepatocellular carcinoma, the clinical implications of the combination of ICIs plus TKIs remain less clear. The phase 3 LEAP-002 trial showed negative results for the combination of the multi-TKI lenvatinib with pembrolizumab. By contrast, CARES-310 was positive for the combination of camrelizumab and rivoceranib; however, the trial recruited mainly in Asia, and rivoceranib is highly VEGFR2 specific, unlike the multi-TKIs currently approved for hepatocellular carcinoma.