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This quadruple combination therapy is being investigated for the treatment of unresectable hepatocellular carcinoma (HCC). It integrates Selective Internal Radiation Therapy (SIRT) using yttrium-90 (Y90) microspheres with a dual immune checkpoint inhibitor regimen (nivolumab and ipilimumab) and a multi-kinase inhibitor (lenvatinib). Y90 microspheres are administered intra-arterially to provide localized beta radiation, which induces tumor necrosis and immunogenic cell death. Nivolumab and ipilimumab are monoclonal antibodies that block the PD-1 and CTLA-4 pathways, respectively, to enhance systemic T-cell activation against tumor cells. Lenvatinib is an oral small molecule that inhibits multiple receptor tyrosine kinases, including VEGFR1-3 and FGFR1-4, thereby suppressing tumor angiogenesis and proliferation. This multi-modal approach, led by West China Hospital, aims to leverage the potential synergy between local radiation, systemic immunotherapy, and anti-angiogenic therapy to improve outcomes in patients with advanced HCC.
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