Abstract
In addition to the monoclonal vascular endothelial growth factor (VEGF) antibody bevacizumab, several alternative anti-angiogenic treatment strategies for ovarian cancer patients have been evaluated in clinical trials. Apart from targeting extracellular receptors by the antibody aflibercept or the peptibody trebananib, the multikinase inhibitors pazopanib, nintedanib, cediranib, sunitinib, and sorafenib were developed to interfere with VEGF receptors and multiple additional intracellular pathways. Nintedanib and pazopanib significantly improved progression-free survival in two positive phase III trials for first-line therapy. A reliable effect on overall survival could, however, not be observed for any anti-angiogenic first-line therapies so far. In terms of recurrent disease, two positive phase III trials revealed that trebananib and cediranib are effective anti-angiogenic agents for this indication. Patient selection and biomarker guided prediction of response seems to be a central aspect for future studies. Combining anti-angiogenics with other targeted therapies to possibly spare chemotherapy in certain constellations represents another very interesting future perspective for clinical trials. This short review gives an overview of current clinical trials for anti-angiogenic treatment strategies beyond bevacizumab. In this context, possible future perspectives combining anti-angiogenics with other targeted therapies and the need for specific biomarkers predicting response are elucidated.
Highlights
With implementation of the monoclonal vascular endothelial growth factor (VEGF) antibody bevacizumab to first-line treatment of ovarian cancer patients, the first targeted anti-angiogenic therapy for this indication has demonstrated efficacy and was approved in several countries
Following promising phase II trials [5], trebananib was investigated for recurrent ovarian cancer in the international, double-blind phase III TRINOVA-1 trial in which weekly paclitaxel 80 mg/m2 was applied with trebananib 15 mg/kg i.v. weekly or placebo [6]
Aflibercept Composed of VEGF binding domains from extracellular regions of the VEGF receptor 1 (VEGFR-1) and VEGFR-2, the fusion protein aflibercept has broad affinity binding VEGF-A, VEGF-B and the placental growth factor (PlGF) [8]
Summary
With implementation of the monoclonal vascular endothelial growth factor (VEGF) antibody bevacizumab to first-line treatment of ovarian cancer patients, the first targeted anti-angiogenic therapy for this indication has demonstrated efficacy and was approved in several countries. Several multikinase inhibitors were developed to interfere with the VEGF receptors and multiple intracellular pathways in addition to the VEGF cascade (e.g., FGF and PDGF), which could be implemented by the introduction of pazopanib, nintedanib, cediranib, sunitinib as well as sorafenib. All these drugs have been studied in clinical trials or are still under investigation. This review gives a focused overview of potential anti-angiogenic treatment strategies beyond bevacizumab and summarizes the current evidence
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
