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Targeting Tumor Vasculature in Ovarian Cancer

Angelica Welch
Published: Wednesday, Dec 27, 2017

Robert L. Coleman, MD
Robert L. Coleman, MD
Angiogenesis inhibition is a process for tumor survival that has been known for many years, says Robert L. Coleman, MD. In ovarian cancer, antiangiogenesis agents have shown particular benefit, as they target tumor vascular biology.

Specifically, the antiangiogenesis agent bevacizumab (Avastin) has been a storied component of the treatment paradigm of ovarian cancer since its approval. More recently, combinations with bevacizumab have been studied in this tumor type, specifically with PARP inhibitors—which have exploded onto the scene these past 2 years.

In an interview with OncLive during the 35th annual CFS®, Coleman, professor, Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, discussed targeting tumor vasculature and angiogenesis in ovarian cancer.

OncLive: Please provide an overview of your lecture on targeting tumor vasculature in ovarian cancer.

Coleman: I started out with a reference from 1907 in Lancet, where there was a question posed looking at the vasculature around cancers—asking why they were there, what role they play, and how to take care of it. I used that as an opening because it was more than a century ago that we recognized there was some relationship, and it was only about half of a century since we started to understand why those processes happen. Even today, it’s a well-acknowledged factor of tumor biology, and how we are approaching treatment is developing science.

Dr Judah Folkman, who many of us think of as a pioneer [of angiogenesis], identified that there were circulating factors in the tumor microenvironment that were actually regulating and controlling the expression and development of blood vessels, and how that related to metastases and invasion. Since then, we have learned that there are multiple factors along the way, and there are different types of angiogenesis. One of the strategies that we have gone after is sort of the lowest-hanging fruit—the growth factor and its receptor. Drugs such as bevacizumab and the tyrosine kinase inhibitors (TKIs) that are targeted at VEGF really emerged on the scene when they showed single-agent activity in multiple different disease types.

In ovarian cancer, we at the Gynecologic Oncology Group (GOG) launched a series of phase II trials that were based on similar eligibility, exclusion criteria, and statistical design. We were looking for that “sweet spot” between activity from response and delay in progression. When you look at the drugs that we have studied, only bevacizumab actually hit both of those endpoints. It was then rapidly developed into the recurrent and frontline setting, and since then, we have had phase III trials that look at bevacizumab, and 9 trials that have looked at other VEGF-targeted therapies that have shown a progression-free survival (PFS) benefit in the frontline and maintenance settings, and in platinum-sensitive and platinum resistant/recurrent disease.

What about other VEGF agents, such as ramucirumab (Cyramza)?

[Ramucirumab] is not being looked at in ovarian yet, but the idea is the same. This is a drug that is an antibody to VEGFR2, which is an important receptor, particularly in gynecologic cancers. In endometrial, ovarian, and cervix cancers, that receptor seems to be important, and we have studied them. Nintedanib (Ofev, Vargatef) and pazopanib (Votrient) are TKIs that have been studied in the phase III setting that also target this receptor.  We have looked at other growth factors such as angiopoietins, which have been investigated. These seem to be important for the endothelial remodeling that happens in the angiogenesis process. It has a similar story about improvement in PFS.

Are there any unanswered questions with bevacizumab in ovarian cancer?

Great question; what do we do next? I always say that we either have to add to it, look at it in sequence, or deal with its adaptive resistance mechanisms to make this strategy better. One of the areas of research that I have been working on for many years now is to try to understand what happens in the microenvironment where the tumors seem to learn how to escape.

View Conference Coverage
Online CME Activities
TitleExpiration DateCME Credits
Oncology Best Practice™: Expert Perspectives to Incorporate Evidence on PARP Inhibitors into Practice and Optimize the Medical Management of Ovarian CancerOct 31, 20181.0
Community Practice Connections™: Precision Medicine for Community Oncologists: Assessing the Role of Tumor-Testing Technologies in Cancer CareNov 30, 20181.0
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