Pazopanib in ovarian cancer

Abstract

The majority of women with ovarian cancer present with advanced disease, and ultimately relapse following primary surgery and platinum-taxane chemotherapy. Despite recent advances in the development of targeted agents in ovarian cancer, survival rates remain poor. The promising activity of bevacizumab, a VEGF receptor inhibitor, has stimulated research on the use of additional anti-angiogenic agents in ovarian cancer. Pazopanib, an oral tyrosine kinase inhibitor, targets VEGF receptor-1, -2 and -3, platelet-derived growth factor receptor-α and -β and c-kit; resulting in the inhibition of angiogenesis and tumor proliferation. Early phase studies have demonstrated promising efficacy and tolerability. To date, there has been one Phase III trial of pazopanib in ovarian cancer, demonstrating a progression-free survival benefit in women treated with maintenance pazopanib following primary surgery and systemic therapy. This article summarizes the preclinical and clinical data of pazopanib in ovarian cancer, highlighting future research options for this agent.

Keywords:

• angiogenesis
• ovarian cancer
• pazopanib
• tyrosine kinase inhibitor

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Angiogenesis is one of the hallmarks of cancer, and is a well-established therapeutic target in ovarian cancer.

• The promising activity of the VEGF receptor inhibitor, bevacizumab in ovarian cancer has stimulated research on the use of additional anti-angiogenic agents.

• Pazopanib is an oral multi-targeted tyrosine kinase inhibitor targeting VEGF receptor-1, -2 and 3, platelet-derived growth factor receptor-α and -β and c-kit, resulting in inhibition of angiogenesis and tumor proliferation.

• Early phase clinical trials of pazopanib have shown promising efficacy and tolerability in ovarian cancer.

• To date, the only Phase III trial of pazopanib in ovarian cancer has shown a modest improvement in progression-free survival, when used as maintenance therapy following primary surgery and platinum-taxane chemotherapy.

• The lack of overall survival benefit and unfavorable toxicity profile of pazopanib in the maintenance setting led to withdrawal of the application for regulatory approval for this indication in Europe.

• Further research in to the optimal use of pazopanib in ovarian cancer is ongoing, particularly the combination of pazopanib with other therapeutic agents.