Beyond Bevacizumab: An Outlook to New Anti-Angiogenics for the Treatment of Ovarian Cancer.
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.
Department of Gynecology and Gynecologic Oncology, University Medical Center Hamburg-Eppendorf , Hamburg , Germany.
Sven
S
Mahner
Department of Gynecology and Gynecologic Oncology, University Medical Center Hamburg-Eppendorf , Hamburg , Germany.
Linn
L
Woelber
Department of Gynecology and Gynecologic Oncology, University Medical Center Hamburg-Eppendorf , Hamburg , Germany.
Volkmar
V
Mueller
Department of Gynecology and Gynecologic Oncology, University Medical Center Hamburg-Eppendorf , Hamburg , Germany.
Isabell
I
Witzel
Department of Gynecology and Gynecologic Oncology, University Medical Center Hamburg-Eppendorf , Hamburg , Germany.
Katharina
K
Prieske
Department of Gynecology and Gynecologic Oncology, University Medical Center Hamburg-Eppendorf , Hamburg , Germany.
Donata
D
Grimm
Department of Oncology, University Medical Center Hamburg-Eppendorf , Hamburg , Germany.
Gunhild
G
Keller-V Amsberg
Department of Gynecology and Gynecologic Oncology, University Medical Center Hamburg-Eppendorf , Hamburg , Germany.
Fabian
F
Trillsch
anti-angiogenic therapy; cediranib; multikinase inhibitors; nintedanib; ovarian cancer; pazopanib; trebananib