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Profile of nintedanib in the treatment of solid tumors: the evidence to date

Authors Awasthi N, Schwarz R

Received 25 August 2015

Accepted for publication 10 November 2015

Published 8 December 2015 Volume 2015:8 Pages 3691—3701

DOI https://doi.org/10.2147/OTT.S78805

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Ram Prasad

Peer reviewer comments 2

Editor who approved publication: Dr Faris Farassati


Niranjan Awasthi,1 Roderich E Schwarz1,2

1Department of Surgery, Indiana University School of Medicine, South Bend, IN, USA; 2Indiana University Health Goshen Center for Cancer Care, Goshen, IN, USA

Abstract: 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.

Keywords: nintedanib, BIBF 1120, angiogenesis, VEGF, tyrosine kinase inhibitors

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