Prevalence and Profiles of Ramucirumab-associated Severe Ascites in Patients with Hepatocellular Carcinoma

Severe ascites is an adverse event of ramucirumab (RAM), a second-line treatment for hepatocellular carcinoma (HCC). Ascites can be associated with various factors, including nutritional status and muscle quality. The aim of the present study was to investigate the prevalence and profiles of RAM-associated severe ascites in patients with HCC. This retrospective study enrolled 14 consecutive patients with HCC treated with RAM (median age, 72 years; Barcelona Clinic Liver Cancer stage B/C, 6/8). Nutritional status and muscle quality were evaluated using the controlling nutritional status (CONUT) score and intramuscular adipose tissue (IMAT) content, respectively. Factors associated with severe ascites were evaluated using decision-tree analysis. The median progression-free survival (PFS) time was 2.1 months, and the overall objective response and disease control rates were 14 and 50%, respectively. Severe ascites developed in 57.1% of the patients, and the median onset was 37.5 days (range, 14-61 days) after initiation of RAM treatment. In the decision-tree analysis, the CONUT score and IMAT content were the first and second splitting variables for the development of severe ascites. In patients with a CONUT score ≥5 and IMAT <-0.54, the prevalence of severe ascites was 80 and 100%, respectively. A high incidence of severe ascites was observed in patients treated with RAM. A CONUT score ≥5 and an IMAT <-0.54 were associated with severe ascites. Thus, caution must be taken for severe ascites in patients with HCC treated with RAM, in particular patients with malnutrition and fat infiltration in muscle.