Phase II, open-label study of brivanib as second-line therapy in patients with advanced hepatocellular carcinoma

Clin Cancer Res. 2012 Apr 1;18(7):2090-8. doi: 10.1158/1078-0432.CCR-11-1991. Epub 2012 Jan 11.

Abstract

Purpose: Brivanib, a selective dual inhibitor of fibroblast growth factor and VEGF signaling, has recently been shown to have activity as first-line treatment for patients with advanced hepatocellular carcinoma (HCC). This phase II open-label study assessed brivanib as second-line therapy in patients with advanced HCC who had failed prior antiangiogenic treatment.

Experimental design: Brivanib was administered orally at a dose of 800 mg once daily. The primary objectives were tumor response rate, time to response, duration of response, progression-free survival, overall survival (OS), disease control rate, time to progression (TTP), and safety and tolerability.

Results: Forty-six patients were treated. Best responses to treatment with brivanib (N = 46 patients) using modified World Health Organization criteria were partial responses for two patients (4.3%), stable disease for 19 patients (41.3%), and progressive disease for 19 patients (41.3%). The tumor response rate was 4.3%; the disease control rate was 45.7%. Median OS was 9.79 months. Median TTP as assessed by study investigators following second-line treatment with brivanib was 2.7 months. The most common adverse events were fatigue, decreased appetite, nausea, diarrhea, and hypertension.

Conclusion: Brivanib had a manageable safety profile and is one of the first agents to show promising antitumor activity in advanced HCC patients treated with prior sorafenib.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Administration, Oral
  • Adult
  • Aged
  • Aged, 80 and over
  • Alanine / adverse effects
  • Alanine / analogs & derivatives*
  • Alanine / therapeutic use
  • Appetite / drug effects
  • Carcinoma, Hepatocellular / blood
  • Carcinoma, Hepatocellular / drug therapy*
  • Collagen Type IV / blood
  • Disease-Free Survival
  • Drug Administration Schedule
  • Fatigue / chemically induced
  • Female
  • Humans
  • Hypertension / chemically induced
  • Liver Neoplasms / blood
  • Liver Neoplasms / drug therapy*
  • Male
  • Middle Aged
  • Nausea / chemically induced
  • Treatment Outcome
  • Triazines / adverse effects
  • Triazines / therapeutic use*
  • Young Adult
  • alpha-Fetoproteins / analysis

Substances

  • AFP protein, human
  • Collagen Type IV
  • Triazines
  • alpha-Fetoproteins
  • brivanib
  • Alanine