{Reference Type}: Clinical Trial, Phase III
{Title}: Ramucirumab as second-line treatment in patients with advanced hepatocellular carcinoma: Japanese subgroup analysis of the REACH trial.
{Author}: Kudo M;Hatano E;Ohkawa S;Fujii H;Masumoto A;Furuse J;Wada Y;Ishii H;Obi S;Kaneko S;Kawazoe S;Yokosuka O;Ikeda M;Ukai K;Morita S;Tsuji A;Kudo T;Shimada M;Osaki Y;Tateishi R;Sugiyama G;Abada PB;Yang L;Okusaka T;Zhu AX;
{Journal}: J Gastroenterol
{Volume}: 52
{Issue}: 4
{Year}: Apr 2017
{Factor}: 6.772
{DOI}: 10.1007/s00535-016-1247-4
{Abstract}: <B>BACKGROUND: </B>REACH evaluated ramucirumab in the second-line treatment of patients with advanced hepatocellular carcinoma. In the intent-to-treat population (n = 565), a significant improvement in overall survival (OS) was not observed. In patients with an elevated baseline α-fetoprotein (AFP) level (400 ng/mL or greater), an improvement in OS was demonstrated. An analysis of the Japanese patients in REACH was performed.<BR><B>METHODS: </B>An analysis was performed with the subset of the intent-to-treat population enrolled in Japan (n = 93).<BR><B>RESULTS: </B>The median OS was 12.9 months for the ramucirumab arm (n = 45) and 8.0 months for the placebo arm (n = 48) [hazard ratio (HR) 0.621 (95 % confidence interval (CI) 0.391-0.986); P = 0.0416]. The median progression-free survival was 4.1 months for the ramucirumab arm and 1.7 months for the placebo arm [HR 0.449 (95 % CI 0.285-0.706); P = 0.0004]. The objective response rates were 11 % for the ramucirumab arm and 2 % for the placebo arm (P = 0.0817). The grade 3 or higher treatment-emergent adverse events occurring in more than 5 % of patients with a higher incidence for the ramucirumab arm (n = 44) than for the placebo arm (n = 47) were ascites (7% vs 2 %), hypertension (7 % vs 2 %), and cholangitis (7 % vs 0 %). In patients with a baseline AFP level of 400 ng/mL or greater, the median OS was 12.9 months for the ramucirumab arm (n = 20) and 4.3 months for the placebo arm (n = 22) [HR 0.464 (95 % CI 0.232-0.926); P = 0.0263].<BR><B>CONCLUSIONS: </B>In the Japanese patients in REACH, ramucirumab treatment improved OS, including in patients with a baseline AFP level of 400 ng/mL or greater; improvements in progression-free survival and objective response rate were also demonstrated. The safety profile of ramucirumab was acceptable and well tolerated in Japanese patients. ClinicalTrials.gov identifier NCT01140347.