Ramucirumab Treatment for Unresectable Advanced Hepatocellular Carcinoma-A Review of Clinical Trial Data and Real-World Evidence in Japan

Ramucirumab was approved in June 2019 in Japan for the treatment of patients with unresectable advanced hepatocellular carcinoma(HCC)with serum alpha-fetoprotein ≥400 ng/mL, whose disease had worsened following chemotherapy. According to the Japan Society of Hepatology clinical practice guidelines for HCC revised in 2021, treatment with ramucirumab is recommended as second-line or subsequent systemic therapy for patients with Child-Pugh class A liver function and serum alpha-fetoprotein ≥400 ng/mL who have discontinued treatment with sorafenib because of radiologic progression or adverse events. To assess the efficacy and safety of treatment with ramucirumab in Japanese clinical practice for patients with unresectable advanced HCC, we reviewed evidence from original articles published after 2019, when ramucirumab was approved as a treatment for HCC in Japan. In addition, we evaluated a pooled data analysis of 2 global phase 3 studies(REACH and REACH-2), in which ramucirumab was administered as second-line therapy after the treatment of sorafenib in patients with unresectable advanced HCC, and the results of the REACH-2 expansion cohort of patients who received ramucirumab after systemic therapy other than sorafenib.