Ramucirumab as second-line treatment in patients with advanced hepatocellular carcinoma: Japanese subgroup analysis of the REACH trial
Tóm tắt
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.
Tài liệu tham khảo
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.
Torre LA, Bray F, Siegel RL, et al. Global cancer statistics, 2012. CA Cancer J Clin. 2015;65:87–108.
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.
Ikeda M, Mitsunaga S, Shimizu S, et al. Current status of hepatocellular carcinoma in Japan. Chin Clin Oncol. 2013;2:40.
Bruix J, Gores GJ, Mazzaferro V. Hepatocellular carcinoma: clinical frontiers and perspectives. Gut. 2014;63:844–55.
Kudo M. Surveillance, diagnosis, treatment, and outcome of liver cancer in Japan. Liver Cancer. 2015;4:39–50.
Kudo M. Clinical practice guidelines for hepatocellular carcinoma differ between Japan, United States and Europe. Liver Cancer. 2015;4:85–95.
Llovet JM, Ricci S, Mazzaferro V, et al. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med. 2008;359:378–90.
Cheng AL, Kang YK, Chen Z, et al. Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: a phase III randomised, double-blind, placebo-controlled trial. Lancet Oncol. 2009;10:25–34.
Lencioni R, Kudo M, Ye SL, et al. GIDEON (Global Investigation of therapeutic DEcisions in hepatocellular carcinoma and Of its treatment with sorafeNib): second interim analysis. Int J Clin Pract. 2014;68:609–17.
Iavarone M, Cabibbo G, Piscaglia F, et al. Field-practice study of sorafenib therapy for hepatocellular carcinoma: a prospective multicenter study in Italy. Hepatology. 2011;54:2055–63.
Sullivan LA, Brekken RA. The VEGF family in cancer and antibody-based strategies for their inhibition. MAbs. 2010;2:165–75.
Tugues S, Koch S, Gualandi L, et al. Vascular endothelial growth factors and receptors: anti-angiogenic therapy in the treatment of cancer. Mol Asp Med. 2011;32:88–111.
Amini A, Masoumi Moghaddam S, Morris DL, et al. The critical role of vascular endothelial growth factor in tumor angiogenesis. Curr Cancer Drug Targets. 2012;12:23–43.
Zhu AX, Duda DG, Sahani DV, et al. HCC and angiogenesis: possible targets and future directions. Nat Rev Clin Oncol. 2011;8:292–301.
Spratlin JL, Cohen RB, Eadens M, et al. Phase I pharmacologic and biologic study of ramucirumab (IMC-1121B), a fully human immunoglobulin G1 monoclonal antibody targeting the vascular endothelial growth factor receptor-2. J Clin Oncol. 2010;28:780–7.
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.
Bruix J, Raoul JL, Sherman M, et al. Efficacy and safety of sorafenib in patients with advanced hepatocellular carcinoma: subanalyses of a phase III trial. J Hepatol. 2012;57:821–9.
Cheng AL, Kang YK, Lin DY, et al. Sunitinib versus sorafenib in advanced hepatocellular cancer: results of a randomized phase III trial. J Clin Oncol. 2013;31:4067–75.
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.
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.
Fuchs CS, Tomasek J, Yong CJ, et al. Ramucirumab monotherapy for previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (REGARD): an international, randomised, multicentre, placebo-controlled, phase 3 trial. Lancet. 2014;383:31–9.
Zhu AX, Finn RS, Mulcahy M, et al. A phase II and biomarker study of ramucirumab, a human monoclonal antibody targeting the VEGF receptor-2, as first-line monotherapy in patients with advanced hepatocellular cancer. Clin Cancer Res. 2013;19:6614–23.