A phase 2 study of the efficacy and biomarker on the combination of transarterial chemoembolization and axitinib in the treatment of inoperable hepatocellular carcinoma

Cancer. 2017 Oct 15;123(20):3977-3985. doi: 10.1002/cncr.30825. Epub 2017 Jun 22.

Abstract

Background: A surge of vascular endothelial growth factor (VEGF) after transarterial chemoembolization (TACE) may contribute to tumor progression. Axitinib is a potent antiangiogenic agent with main activity against VEGF receptors 1 to 3. To the authors' knowledge, its role in combination with TACE for the treatment of patients with inoperable hepatocellular carcinoma (HCC) is unclear.

Methods: A phase 2 clinical trial (ClinicalTrials.gov identifier NCT01352728) was conducted to evaluate the combination treatment. Patients with inoperable HCC who were potential candidates for TACE initiated treatment with axitinib at a dose of 5 mg twice daily and were evaluated for the need for TACE every 8 weeks. Axitinib was withheld 24 hours before TACE, and resumed 24 hours afterward when fulfilling predefined criteria. Radiologic assessment was conducted every 8 weeks. The primary endpoint was the 2-year overall survival (OS) rate.

Results: A total of 50 patients were recruited from March 2011 to April 2014. The mean age of the patients was 61.8 years, and 46 patients (92%) had hepatitis B infection. The Barcelona Clinic Liver Cancer stage B/C percentage was 76% (38 cases)/24% (12 cases). The 2-year OS rate was 43.7%, and the median OS was 18.8 months in the intention-to-treat population. Among the evaluable population (44 patients), 40.9% (18 patients) and 27.3% (12 patients) achieved complete and partial responses, respectively. Common grade 3 or above axitinib-related complications included hand-foot skin reaction (14%) and hypertension (24%). The presence of hypertension during treatment was found to be an independent prognosticator (hazard ratio, 0.563; P = .0073) suggestive of a contributory role of axitinib to efficacy.

Conclusions: The combination of axitinib and TACE was potentially efficacious for patients with inoperable HCC with a high radiologic response rate. Cancer 2017;123:3977-85. © 2017 American Cancer Society.

Keywords: cancer; drug development; hypertension; interventional radiology; liver.

Publication types

  • Clinical Trial, Phase II

MeSH terms

  • Aged
  • Alanine Transaminase / metabolism
  • Alkaline Phosphatase / metabolism
  • Antineoplastic Agents / administration & dosage*
  • Axitinib
  • Bilirubin / metabolism
  • Carcinoma, Hepatocellular / metabolism
  • Carcinoma, Hepatocellular / pathology
  • Carcinoma, Hepatocellular / therapy*
  • Chemoembolization, Therapeutic / methods*
  • Disease Progression
  • Disease-Free Survival
  • Female
  • Humans
  • Imidazoles / therapeutic use*
  • Indazoles / therapeutic use*
  • International Normalized Ratio
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / pathology
  • Liver Neoplasms / therapy*
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Proportional Hazards Models
  • Protein Kinase Inhibitors / therapeutic use*
  • Receptors, Vascular Endothelial Growth Factor / antagonists & inhibitors
  • Survival Rate
  • Treatment Outcome
  • Tumor Burden

Substances

  • Antineoplastic Agents
  • Imidazoles
  • Indazoles
  • Protein Kinase Inhibitors
  • Axitinib
  • Alanine Transaminase
  • Receptors, Vascular Endothelial Growth Factor
  • Alkaline Phosphatase
  • Bilirubin

Associated data

  • ClinicalTrials.gov/NCT01352728