Safety and efficacy of tigatuzumab plus sorafenib as first-line therapy in subjects with advanced hepatocellular carcinoma: A phase 2 randomized study

被引：51

作者：

Cheng, Ann-Lii ^{[1
]}

Kang, Yoon-Koo ^{[2
]}

He, Aiwu Ruth ^{[3
]}

Lim, Ho Yeong ^{[4
]}

Ryoo, Baek-Yeol ^{[2
]}

Hung, Chao-Hung ^{[5
]}

Sheen, I-Shyan ^{[6
]}

Izumi, Namiki ^{[7
]}

Austin, TaShara ^{[8
]}

Wang, Qiang ^{[9
]}

Greenberg, Jonathan ^{[9
]}

Shiratori, Shinichi ^{[9
]}

Beckman, Robert A. ^{[10
,11
,12
,13
]}

Kudo, Masatoshi ^{[14
]}

机构：

[1] Natl Taiwan Univ Hosp, Dept Oncol, Taipei, Taiwan

[2] Univ Ulsan, Coll Med, Asan Med Ctr, Dept Oncol, Seoul, South Korea

[3] Georgetown Univ, Med Ctr, Lombardi Comprehens Canc Ctr, Washington, DC 20007 USA

[4] Sungkyunkwan Univ, Samsung Med Ctr, Seoul, South Korea

[5] Chang Gung Med Fdn Kaohsiung, Kaohsiung, Taiwan

[6] Chang Gung Med Fdn Linkuo, Taoyaun, Taiwan

[7] Japan Red Cross Musashino Hosp, Tokyo, Japan

[8] Novartis Pharmaceut, E Hanover, NJ USA

[9] Daiichi Sankyo Pharma Dev, Edison, NJ USA

[10] Georgetown Univ, Med Ctr, Dept Oncol, Lombardi Comprehens Canc Ctr, Washington, DC 20007 USA

[11] Georgetown Univ, Med Ctr, Innovat Ctr Biomed Informat, Washington, DC 20007 USA

[12] Georgetown Univ, Med Ctr, Dept Biostat Bioinformat & Biomath, Lombardi Comprehens Canc Ctr, Washington, DC 20007 USA

[13] Georgetown Univ, Med Ctr, Innovat Ctr Biomed Informat, Washington, DC 20007 USA

[14] Kinki Univ Hosp, Osaka, Japan

来源：

JOURNAL OF HEPATOLOGY | 2015年 / 63卷 / 04期

关键词：

Advanced hepatocellular carcinoma; Combination therapy; CS-1008; Monoclonal antibody; Sorafenib; Tigatuzumab; MULTIKINASE INHIBITOR; TRAIL SENSITIZATION; CLINICAL-TRIALS; SOLID TUMORS; ANTIBODY; CELLS; CS-1008; CANCER; MCL-1; CHEMOTHERAPY;

D O I：

10.1016/j.jhep.2015.06.001

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

摘要：

Background & Aims: Tigatuzumab is a humanized monoclonal antibody that acts as a death receptor-5 agonist and exerts tumour necrosis factor-related apoptosis-inducing ligand-like activity. In this phase II study, safety and tolerability of the combination of tigatuzumab and sorafenib was evaluated in patients with advanced hepatocellular carcinoma. Methods: Adults with advanced hepatocellular carcinoma, measurable disease, and an Eastern Cooperative Oncology Group performance score <= 1 were enrolled. Eligible subjects were randomly assigned 1: 1: 1 to tigatuzumab (6 mg/kg loading, 2 mg/kg/week maintenance) plus sorafenib 400 mg twice daily; tigatuzumab (6 mg/kg loading, 6 mg/kg/week maintenance) plus sorafenib 400 mg twice daily; or sorafenib 400 mg twice daily. The primary end point was time to progression. Secondary end points included overall survival and safety. Results: 163 subjects were randomized to treatment. Median time to progression was 3.0 months in the tigatuzumab 6/2 mg/kg combination group (p = 0.988 vs. sorafenib), 3.9 months in the tigatuzumab 6/6 mg/kg combination group (p = 0.586 vs. sorafenib), and 2.8 months in the sorafenib alone group. Median overall survival was 12.2 months in the tigatuzumab 6/6 mg/kg combination group (p = 0.659 vs. sorafenib), vs. 8.2 months in both other treatment groups (p = 0.303, tigatuzumab 6/2 mg/kg combination vs. sorafenib). The most common treatment-emergent adverse events were palmar-plantar erythrodysesthesia syndrome, diarrhea, and decreased appetite. Conclusions: Tigatuzumab combined with sorafenib vs. sorafenib alone in adults with advanced hepatocellular carcinoma did not meet its primary efficacy end point, although tigatuzumab plus sorafenib is well tolerated in hepatocellular carcinoma. (C) 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

引用

页码：896 / 904

页数：9

共 29 条

[1] Hepatocellular Carcinoma Incidence, Mortality, and Survival Trends in the United States From 1975 to 2005 [J].