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

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.

• Authors: Ann-Lii Cheng, Yoon-Koo Kang, Aiwu Ruth He, Ho Yeong Lim, Baek-Yeol Ryoo, Chao-Hung Hung, I-Shyan Sheen, Namiki Izumi, TaShara Austin, Qiang Wang, Jonathan Greenberg, Shinichi Shiratori, Robert A Beckman, Masatoshi Kudo, Investigators’ Study Group
• Journal: Journal of hepatology (J Hepatol) Vol. 63 Issue 4 Pg. 896-904 (Oct 2015) ISSN: 1600-0641 [Electronic] Netherlands
• PMID: 26071796 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Chemical References

• Antibodies, Monoclonal, Humanized
• Antineoplastic Agents
• Phenylurea Compounds
• tigatuzumab
• Niacinamide
• Sorafenib
• Receptors, Vascular Endothelial Growth Factor

Topics

• Adult
• Aged
• Aged, 80 and over
• Antibodies, Monoclonal, Humanized (administration & dosage)
• Antineoplastic Agents (administration & dosage)
• Carcinoma, Hepatocellular (drug therapy, pathology)
• Disease-Free Survival
• Dose-Response Relationship, Drug
• Drug Administration Schedule
• Drug Therapy, Combination
• Female
• Follow-Up Studies
• Humans
• Liver Neoplasms (drug therapy, pathology)
• Male
• Middle Aged
• Neoplasm Staging
• Niacinamide (administration & dosage, analogs & derivatives)
• Phenylurea Compounds (administration & dosage)
• Receptors, Vascular Endothelial Growth Factor
• Retrospective Studies
• Sorafenib
• Time Factors
• Treatment Outcome