Nintedanib in ovarian cancer

ABSTRACT

Introduction: Advanced ovarian cancer remains an unmet clinical need. Angiogenesis is considered a therapeutic target in ovarian cancer, with bevacizumab, a monoclonal antibody against VEGF, being the first drug to show a progression-free survival benefit. Nintedanib is an oral tyrosine kinase inhibitor targeting VEGF receptor 1–3, FGFR 1–3 and PDGFR α and β, which has entered phase III trial development in ovarian cancer.

Areas covered: This article reviews the preclinical and clinical efficacy of nintedanib in ovarian cancer, its pharmacokinetic and pharmacodynamics profile, safety issues, together with an overview of clinical trials carried out so far. A literature search was made in PubMed for nintedanib, ovarian cancer, angiogenesis, and on ClinicalTrials.gov site for clinical trials with nintedanib.

Expert opinion: An ongoing phase III trial investigating nintedanib combined with first-line chemotherapy in ovarian cancer has shown a statistically significant progression free survival benefit, although there were toxicity issues. The true clinical benefit of nintedanib in ovarian cancer including its optimal treatment setting and dosage still need to be addressed.

KEYWORDS:

• Nintedanib
• ovarian cancer
• angiogenesis inhibitor
• VEGFR tyrosine kinase inhibitor

Article Highlights

• Nintedanib is an oral triple angiokinase inhibitor that targets VEGFR 1-3, PDGFR α β and FGFR 1-3, which has shown kinase inhibition resulting in inhibition of proliferation, pro-apoptosis and anti-angiogenesis activity.

• The first phase III trial combing nintedanib with standard first-line chemotherapy and as maintenance therapy reported a statistically significant, albeit relatively small, improvement in PFS.

Identification of the role of nintedanib in ovarian cancer therapy requires further investigation and trial results are pending.

Acknowledgments

The authors would like to thank The Royal Marsden NHS Foundation Trust, The Institute of Cancer Research, National Institute for Health Research (NIHR), Biomedical Research Centre for Cancer (BRC) and The Monument Trust.

Declaration of interest

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.