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Emerging treatments and combinations in the management of NSCLC: clinical potential of nintedanib.

Reck M, Mellemgaard A - Biologics (2015)

Bottom Line: There remains an unmet need for effective, well-tolerated treatment options in advanced non-small cell lung cancer (NSCLC) to alleviate the disease burden for a broad selection of patients.In this study, which led to the approval of nintedanib, addition of nintedanib to docetaxel significantly improved overall survival in patients with adenocarcinoma histology.Nintedanib demonstrated a manageable safety profile in combination with docetaxel.

View Article: PubMed Central - PubMed

Affiliation: Department of Thoracic Oncology, Lung Clinic Grosshansdorf, and member of the Airway Research Center North, German Center for Lung Research, Grosshansdorf, Germany.

ABSTRACT
There remains an unmet need for effective, well-tolerated treatment options in advanced non-small cell lung cancer (NSCLC) to alleviate the disease burden for a broad selection of patients. Nintedanib is a potent, oral, triple angiokinase inhibitor of vascular endothelial growth factor, fibroblast growth factor, and platelet-derived growth factor, and was recently approved in Europe for use in combination with docetaxel for the treatment of adults with locally advanced, metastatic, or locally recurrent NSCLC of adenocarcinoma tumor histology, following first-line chemotherapy. Nintedanib has been investigated extensively in preclinical research and in a number of clinical studies, the most important of which was the Phase III LUME-Lung 1 study, which investigated nintedanib in combination with docetaxel in patients with advanced NSCLC after failure of first-line chemotherapy. In this study, which led to the approval of nintedanib, addition of nintedanib to docetaxel significantly improved overall survival in patients with adenocarcinoma histology. Nintedanib demonstrated a manageable safety profile in combination with docetaxel. This review focuses on the clinical experience with nintedanib in NSCLC and discusses the clinical potential of this agent for use in combination with chemotherapy.

No MeSH data available.


Related in: MedlinePlus

X-ray structure of nintedanib bound in the active site of the vascular endothelial growth factor receptor 2 crystal.Note: Reprinted from Cancer Research, 2008;68(12):4774–4782, Hilberg F, Roth GJ, Krssak M, et al, BIBF 1120: triple angiokinase inhibitor with sustained receptor blockade and good antitumor efficacy, with permission from AACR.18
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f1-btt-9-047: X-ray structure of nintedanib bound in the active site of the vascular endothelial growth factor receptor 2 crystal.Note: Reprinted from Cancer Research, 2008;68(12):4774–4782, Hilberg F, Roth GJ, Krssak M, et al, BIBF 1120: triple angiokinase inhibitor with sustained receptor blockade and good antitumor efficacy, with permission from AACR.18

Mentions: Nintedanib is a 6-methoxycarbonyl-substituted indolinone derivative that was identified in a chemical lead optimization program for ATP-competitive inhibitors of VEGF receptor 2 and other proangiogenic receptor tyrosine kinases.18–20 The binding of nintedanib to VEGF receptor 2 was confirmed by X-ray crystallography and was shown to occur in the intracellular ATP-binding site in the cleft between the NH2 and COOH terminal lobes of the kinase domain (Figure 1).18


Emerging treatments and combinations in the management of NSCLC: clinical potential of nintedanib.

Reck M, Mellemgaard A - Biologics (2015)

X-ray structure of nintedanib bound in the active site of the vascular endothelial growth factor receptor 2 crystal.Note: Reprinted from Cancer Research, 2008;68(12):4774–4782, Hilberg F, Roth GJ, Krssak M, et al, BIBF 1120: triple angiokinase inhibitor with sustained receptor blockade and good antitumor efficacy, with permission from AACR.18
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4494183&req=5

f1-btt-9-047: X-ray structure of nintedanib bound in the active site of the vascular endothelial growth factor receptor 2 crystal.Note: Reprinted from Cancer Research, 2008;68(12):4774–4782, Hilberg F, Roth GJ, Krssak M, et al, BIBF 1120: triple angiokinase inhibitor with sustained receptor blockade and good antitumor efficacy, with permission from AACR.18
Mentions: Nintedanib is a 6-methoxycarbonyl-substituted indolinone derivative that was identified in a chemical lead optimization program for ATP-competitive inhibitors of VEGF receptor 2 and other proangiogenic receptor tyrosine kinases.18–20 The binding of nintedanib to VEGF receptor 2 was confirmed by X-ray crystallography and was shown to occur in the intracellular ATP-binding site in the cleft between the NH2 and COOH terminal lobes of the kinase domain (Figure 1).18

Bottom Line: There remains an unmet need for effective, well-tolerated treatment options in advanced non-small cell lung cancer (NSCLC) to alleviate the disease burden for a broad selection of patients.In this study, which led to the approval of nintedanib, addition of nintedanib to docetaxel significantly improved overall survival in patients with adenocarcinoma histology.Nintedanib demonstrated a manageable safety profile in combination with docetaxel.

View Article: PubMed Central - PubMed

Affiliation: Department of Thoracic Oncology, Lung Clinic Grosshansdorf, and member of the Airway Research Center North, German Center for Lung Research, Grosshansdorf, Germany.

ABSTRACT
There remains an unmet need for effective, well-tolerated treatment options in advanced non-small cell lung cancer (NSCLC) to alleviate the disease burden for a broad selection of patients. Nintedanib is a potent, oral, triple angiokinase inhibitor of vascular endothelial growth factor, fibroblast growth factor, and platelet-derived growth factor, and was recently approved in Europe for use in combination with docetaxel for the treatment of adults with locally advanced, metastatic, or locally recurrent NSCLC of adenocarcinoma tumor histology, following first-line chemotherapy. Nintedanib has been investigated extensively in preclinical research and in a number of clinical studies, the most important of which was the Phase III LUME-Lung 1 study, which investigated nintedanib in combination with docetaxel in patients with advanced NSCLC after failure of first-line chemotherapy. In this study, which led to the approval of nintedanib, addition of nintedanib to docetaxel significantly improved overall survival in patients with adenocarcinoma histology. Nintedanib demonstrated a manageable safety profile in combination with docetaxel. This review focuses on the clinical experience with nintedanib in NSCLC and discusses the clinical potential of this agent for use in combination with chemotherapy.

No MeSH data available.


Related in: MedlinePlus