Vandetanib in patients with inoperable hepatocellular carcinoma: a phase II, randomized, double-blind,
Chiun Hsu1, Tsai-Sheng Yang2, Teh-Ia Huo3
1Departments of Oncology and Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
Background & Aims:
Inhibitors of vascular endothelial growth factor receptor (VEGFR) and epidermal growth factor receptor (EGFR) have shown anti-tumor activities in advanced hepatocellular carcinoma (HCC). The present study evaluated the efficacy and safety of vandetanib, an oral inhibitor of both VEGFR and EGFR, in patients with unresectable advanced HCC.
Methods:
Eligible patients were randomized 1:1:1 to receive vandetanib 300mg/day, vandetanib 100mg/day, or placebo. Upon disease progression, all patients had the option to receive open-label vandetanib 300mg/day. The primary objective was to evaluate tumor stabilization rate (complete response+partial response+stable disease ⩾4months). Secondary assessments included progression-free survival (PFS), overall survival (OS) and safety. Biomarker studies included circulating pro-angiogenic factors and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI).
Results:
Sixty-seven patients were randomized to vandetanib 300mg (n=19), vandetanib 100mg (n=25) or placebo (n=23) groups. Twenty-nine patients entered open-label treatment. Vandetanib induced a significant increase in circulating VEGF and decrease in circulating VEGFR levels. In both vandetanib arms, tumor stabilization rate was not significantly different from placebo: 5.3% (vandetanib 300mg), 16.0% (vandetanib 100mg) and 8.7% (placebo). DCE-MRI did not detect significant vascular change after vandetanib treatment. Although trends of improved PFS and OS after vandetanib treatment were found, they were statistically insignificant. The most common adverse events were diarrhea and rash, whose incidence did not differ significantly between treatment groups.
Conclusions:
Vandetanib has limited clinical activity in HCC. The safety profile was consistent with previous studies.
Insights
Vandetanib, an inhibitor of VEGFR and EGFR, showed limited efficacy in advanced hepatocellular carcinoma (HCC). The drug did not significantly improve tumor stabilization, progression-free survival, or overall survival compared to placebo.
Area of Science:
- Oncology
- Pharmacology
Background:
- Vascular endothelial growth factor receptor (VEGFR) and epidermal growth factor receptor (EGFR) inhibitors demonstrate anti-tumor activity in advanced hepatocellular carcinoma (HCC).
- Vandetanib is an oral inhibitor targeting both VEGFR and EGFR.
Purpose of the Study:
- To evaluate the efficacy and safety of vandetanib in patients with unresectable advanced HCC.
- To assess tumor stabilization rate, progression-free survival (PFS), and overall survival (OS).
Main Methods:
- Randomized, double-blind trial comparing vandetanib (300mg or 100mg daily) to placebo.
- Patients could receive open-label vandetanib upon disease progression.
- Primary endpoint: tumor stabilization rate (≥4 months). Secondary endpoints: PFS, OS, safety, and biomarker analysis (circulating factors, DCE-MRI).
Main Results:
- No significant difference in tumor stabilization rate between vandetanib arms and placebo.
- Vandetanib increased circulating VEGF and decreased VEGFR levels, but DCE-MRI showed no significant vascular changes.
- Trends towards improved PFS and OS were observed but not statistically significant. Adverse events (diarrhea, rash) were similar across groups.
Conclusions:
- Vandetanib demonstrated limited clinical activity in advanced HCC.
- The safety profile of vandetanib in this study was consistent with prior research.
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