Angiogenesis is an essential process for
tumor growth and
metastasis, and remains a promising therapeutic target process in
cancer treatment for several
cancer types.
Bevacizumab, a
monoclonal antibody that targets
vascular endothelial growth factor (
VEGF), was the first
antiangiogenic agent approved for
cancer therapy. Novel
antiangiogenic agents, such as
sunitinib,
sorafenib,
pazopanib, or
vandetanib that target additional proangiogenic signaling pathways beyond
VEGF, have also been approved for the treatment of various malignant diseases. While most of these agents are approved in combination with cytotoxic
chemotherapy for indications including metastatic
colorectal cancer,
non-small-cell lung cancer,
breast cancer,
renal cell carcinoma (RCC), and
gastric cancer, some are used as approved monotherapy for advanced RCC,
hepatocellular carcinoma and
medullary thyroid cancer. Major challenges to the success of antiangiogenic
therapy include associated toxicity risks, limitation of efficacy through the possible development of resistance and induction or promotion of metastatic progression.
Nintedanib (formally known as
BIBF 1120) is a triple angiokinase inhibitor of
VEGF,
fibroblast growth factor,
platelet-derived growth factor signaling with lesser activity against RET, Flt-3, and Src. Through this unique targeting profile
nintedanib has demonstrated significant antitumor activity in several
tumor types in preclinical studies.
Nintedanib has also shown promising clinical efficacy in combination with
docetaxel and has been approved for treating patients with locally advanced and metastatic
non-small-cell lung cancer in Europe.
Nintedanib has also been found to be clinically promising in terms of efficacy and safety in several other solid
tumors including
ovarian cancer (Phase III), RCC (Phase II), and
prostate cancer (Phase II). This review article provides a comprehensive summary of the preclinical and clinical efficacy of
nintedanib in the treatment of solid
tumors.