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Second-line treatments have also been designed over the past few years, including regorafenib (antiangiogenesis) (Bruix et al., 2017), nivolumab [against the programed cell death-1 (PD1) immune checkpoint] (El-Khoueiry et al., 2017), and ramucirumab (against VEGFR2) (Zhu et al., 2019)