Ramucirumab as second-line treatment in patients with advanced hepatocellular carcinoma: Japanese subgroup analysis of the REACH trial
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.
An analysis was performed with the subset of the intent-to-treat population enrolled in Japan (n = 93).
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].
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.
Keywordsα-Fetoprotein Clinical trial Japan Liver neoplasms Vascular endothelial growth factor receptor 2
- 1.Ferlay J, Soerjomataram I, Ervik M, et al. GLOBOCAN 2012 v1.0. Estimated cancer incidence, mortality and prevalence worldwide in 2012: liver cancer. CancerBase no. 11. Lyon: International Agency for Research on Cancer. Available via http://globocan.iarc.fr/Pages/fact_sheets_cancer.aspx. Accessed 13 Feb 2015.
- 3.Kudo M, Lencioni R, Marrero JA, et al. Regional differences in sorafenib-treated patients with hepatocellular carcinoma: GIDEON observational study. Liver Int. 2016. doi:10.1111/liv.13096.
- 17.Zhu AX, Park JO, Ryoo BY, et al. Ramucirumab versus placebo as second-line treatment in patients with advanced hepatocellular carcinoma following first-line therapy with sorafenib (REACH): a randomised, double-blind, multicentre, phase 3 trial. Lancet Oncol. 2015;16:859–70.CrossRefPubMedGoogle Scholar
- 20.Hironaka S, Shimada Y, Sugimoto N, et al. RAINBOW: a global, phase III, randomized, double-blind study of ramucirumab (RAM) plus paclitaxel (PTX) versus placebo (PL) plus PTX in the treatment of metastatic gastroesophageal junction and gastric adenocarcinoma (mGC) following disease progression on first-line platinum- and fluoropyrimidine-containing combination therapy—efficacy analysis in Japanese and Western patients. J Clin Oncol. 2014;32(15 Suppl):4005.Google Scholar
- 21.Muro K, Cheul Oh S, et al. Subgroup analysis of East Asians in RAINBOW: a phase 3 trial of ramucirumab plus paclitaxel for advanced gastric cancer. J Gastroenterol Hepatol. 2015. doi: 10.1111/jgh.13153.