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J Hepatol. 2015 Oct;63(4):896-904. doi: 10.1016/j.jhep.2015.06.001. Epub 2015 Jun 10.

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

Author information

1
Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan. Electronic address: alcheng@ntu.edu.tw.
2
Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
3
Georgetown University Medical Center, Lombardi Comprehensive Cancer Center, Washington, DC, USA.
4
Samsung Medical Center, Sungkyunkwan University, Seoul, Republic of Korea.
5
Chang Gung Medical Foundation-Kaohsiung, Kaohsiung, Taiwan.
6
Chang Gung Medical Foundation-Linkuo, Taoyaun, Taiwan.
7
Japan Red Cross Musashino Hospital, Tokyo, Japan.
8
Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA.
9
Daiichi Sankyo Pharma Development, Edison, NJ, USA.
10
Department of Oncology, Lombardi Comprehensive Cancer Center and Innovation Center for Biomedical Informatics, Georgetown University Medical Center, Washington, DC, USA; Department of Biostatistics, Bioinformatics, and Biomathematics, Lombardi Comprehensive Cancer Center and Innovation Center for Biomedical Informatics, Georgetown University Medical Center, Washington, DC, USA.
11
Kinki University Hospital, Osaka, Japan.

Abstract

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.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT01033240.

KEYWORDS:

Advanced hepatocellular carcinoma; CS-1008; Combination therapy; Monoclonal antibody; Sorafenib; Tigatuzumab

PMID:
26071796
DOI:
10.1016/j.jhep.2015.06.001
[Indexed for MEDLINE]

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