Anti-angiogenic therapy for ovarian cancer

LBA5500 Background: PARP inhibitors and anti-angiogenics are clinically active in recurrent ovarian cancer (OvCa). Preclinical studies suggest these agents can synergize, and a phase 1 study showed that the combination of cediranib (ced) and olaparib (olap) is well-tolerated. We therefore compared the activity of olap alone (Olap) to combined ced and olap (Ced/Olap) in treatment of recurrent platinum-sensitive (plat-sens) high-grade serous (HGS) or BRCA-related OvCa (NCT 01116648). Methods: Patients (pts) across 9 centers were randomized 1:1 in this Ph 2 open label study to Olap (olap 400 mg capsules BID) or Ced/Olap (olap 200 mg capsules BID; ced 30 mg daily), stratified by BRCA status and prior anti-angiogenic therapy. Eligibility included pts with recurrent plat-sens HGS or BRCA-related OvCa. Pts had measurable disease by RECIST 1.1, PS 0 or 1, and the ability to take POs. No prior anti-angiogenics in the recurrent setting or prior PARP inhibitor was allowed. Progression-free survival (PFS) was defined as time from randomization to radiographic progression or death. With a target N=90 pts, the study was powered to detect a hazard ratio (HR) of 1.75 (median PFS 6 vs 10.5 mo). Results: Pts were enrolled from Oct 2011 to Jun 2013: 46 to Olap, 44 to Ced/Olap. 48 pts were known BRCA carriers (25 Olap; 23 Ced/Olap). At a planned interim analysis the DSMB recommended release of data. As of Jan 7, 2014, 41 pts had a PFS event. Median PFS was 9.0 mos for Olap and 17.7 mos for Ced/Olap (HR 2.9, 95% CI 1.5-5.6, p = 0.001). There were 2 complete responses (CR) and 21 partial responses (PR) in pts on Olap (56% objective response rate, ORR) and 3 CRs and 33 PRs in pts on Ced/Olap (84% ORR, p = 0.008). The overall rate of Gr3/4 toxicity was higher for pts on Ced/Olap (70%) than on Olap (7%). Differentially occurring toxicities included fatigue (27% Ced/Olap vs 7% Olap), diarrhea (23% vs 0%), and hypertension (39% vs 0%). Updated efficacy and exploratory subgroup analyses will be presented. Conclusions: Combined Ced/Olap significantly extended PFS and ORR compared to Olap in plat-sens OvCa. Further studies of this oral combination in plat-sens OvCa are warranted. Clinical trial information: NCT01116648.

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Evaluation of Potentially Predictive Markers for Anti-Angiogenic Therapy with Sunitinib in Recurrent Ovarian Cancer Patients

Translational Oncology ◽

10.1593/tlo.13205 ◽

2013 ◽

Vol 6 (3) ◽

pp. 305-310 ◽

Cited By ~ 8

Author(s):

Dirk O Bauerschlag ◽

Felix Hilpert ◽

Werner Meier ◽

Jörn Rau ◽

Ivo Meinhold-Heerlein ◽

...

Keyword(s):

Ovarian Cancer ◽

Cancer Patients ◽

Recurrent Ovarian Cancer ◽

Predictive Markers ◽

Angiogenic Therapy

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Biological Pathways Involved in Tumor Angiogenesis and Bevacizumab Based Anti-Angiogenic Therapy with Special References to Ovarian Cancer

International Journal of Molecular Sciences ◽

10.3390/ijms18091967 ◽

2017 ◽

Vol 18 (9) ◽

pp. 1967 ◽

Cited By ~ 30

Author(s):

Vera Loizzi ◽

Vittoria Del Vecchio ◽

Giulio Gargano ◽

Maria De Liso ◽

Anila Kardashi ◽

...

Keyword(s):

Ovarian Cancer ◽

Tumor Angiogenesis ◽

Biological Pathways ◽

Angiogenic Therapy

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Markers of Angiogenesis in Ovarian Cancer

Disease Markers ◽

10.1155/2007/257602 ◽

2007 ◽

Vol 23 (5-6) ◽

pp. 419-431 ◽

Cited By ~ 14

Author(s):

William M. Merritt ◽

Anil K. Sood

Keyword(s):

Ovarian Cancer ◽

Ovarian Carcinoma ◽

Potential Role ◽

Tumor Development ◽

Prognostic Information ◽

Angiogenic Therapy ◽

Density Analysis ◽

Monitoring Response ◽

Potential Biomarkers

Tumor development and progression are inherently dependent on the process of angiogenesis. Recently, anti-angiogenic therapy has started to show promise as an effective treatment strategy in many solid tumors including ovarian carcinoma. Unfortunately, lack of effective biomarkers presents a challenge for oncologists in treatment planning as well as monitoring response of new anti-vascular agents. Previously, quantification of angiogenesis by microvessel density analysis provided useful prognostic information, however, its utility following anti-angiogenic therapy remains to be determined. Moreover, since secreted cytokines play an active part in angiogenesis by mediating neovascularization in tumors, investigations have focused on their potential role to serve as candidate biomarkers of disease detection, prognosis, and treatment response. In this article, we review the role of key angiogenesis markers as potential biomarkers in ovarian carcinoma.

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Modern aspects of antiangiogenic therapy in ovarian cancer

Medical Council ◽

10.21518/2079-701x-2018-19-17-21 ◽

2018 ◽

pp. 17-21

Author(s):

A. A. Rumyantsev ◽

I. A. Pokataev ◽

S. A. Tyulyandin

Keyword(s):

Ovarian Cancer ◽

Standard Treatment ◽

Antiangiogenic Therapy ◽

Malignant Tumours ◽

Angiogenic Therapy

The process of angiogenesis is essential for the growth and spread of malignant tumours. Antiangiogenic therapy is deeply embedded in the standard treatment of disseminated ovarian cancer (OC). The numerous studies have demonstrated its efficacy in various stages of the therapy of this disease; bevacizumab is the best-investigated anti-angiogenic drug for OC. This article presents a review and analysis of the most significant studies of the efficacy of anti-angiogenic therapy in ovarian cancer, and describes various aspects of its use in this disease.

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