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Development of sunitinib in hepatocellular carcinoma: rationale, early clinical experience, and correlative studies

Andrew X Zhu1, Dan G Duda, Dushyant V Sahani

  • 1Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USA. azhu@partners.org

Cancer Journal (Sudbury, Mass.)
|August 13, 2009
PubMed

Insights

Sunitinib, a multitargeted kinase inhibitor, shows early promise for advanced hepatocellular carcinoma (HCC). Ongoing trials are evaluating its efficacy and safety compared to sorafenib in HCC patients.

Area of Science:

  • Oncology
  • Pharmacology
  • Molecular Biology

Background:

  • Sorafenib, a multitargeted receptor tyrosine kinase inhibitor, marked the advent of targeted therapy for advanced hepatocellular carcinoma (HCC).
  • Sunitinib malate is an oral multitargeted inhibitor targeting kinases crucial for tumor growth, angiogenesis, and metastasis.

Purpose of the Study:

  • To review the current progress and future directions for sunitinib development in advanced HCC.
  • To assess the early evidence of antitumor activity and safety profile of sunitinib in advanced HCC.

Main Methods:

  • Phase II trials in United States, European, and Asian patients with advanced HCC.
  • Correlative studies utilizing imaging and circulating biomarkers to understand sunitinib's mechanism of action.
  • Ongoing Phase II studies evaluating sunitinib as a single agent or in combination with chemotherapy.
  • An active Phase III trial comparing sunitinib with sorafenib in advanced HCC.

Main Results:

  • Early evidence from single-arm Phase II trials indicates antitumor activity for sunitinib in advanced HCC.
  • Sunitinib demonstrates a promising safety profile in diverse patient populations.
  • Biomarker studies offer insights into the potential mechanisms underlying sunitinib's efficacy.

Conclusions:

  • Sunitinib represents a potential new therapeutic option for advanced HCC.
  • Further clinical development, including combination therapies and head-to-head trials with sorafenib, is warranted.
  • Understanding the mechanism of action through biomarker studies will aid in optimizing sunitinib treatment strategies.

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