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Antiangiogenic agents in advanced, persistent or recurrent endometrial cancer: a novel treatment option
Angiolo Gadducci1, Claudia Sergiampietri, Ilaria Guiggi
1Department of Clinical and Experimental Medicine, Division of Gynecology and Obstetrics, University of Pisa, Pisa 56127, Italy. a.gadducci@obgyn.med.unipi.it
Abstract:
The limited efficacy of endocrine therapy and chemotherapy has stimulated several researches aimed to detect novel molecularly target therapies for advanced, persistent or recurrent endometrial cancer. Prior attempts to block vascular endothelial growth factor (VEGF) with sunitinib, sorafenib and thalidomide have obtained disappointing results. Bevacizumab has shown a promising activity in a phase II study. The percentages of patients with progression-free survival ≥6 months were similar for endometrioid (35%) and serous carcinoma (36%), but the number of cases was too small to assess the relevance of histological type for response to bevacizumab. In a phase II study, aflibercept was administered every 2 weeks to women with recurrent or persistent disease after chemotherapy. Forty-one percent of the patients were progression-free at 6 months, but 32% of the women had been removed from study because of toxicity. The detection of activating mutations of Fibroblast Growth Factor Receptor (FGFR)-2 in primary endometrial carcinoma has generated a new avenue for the development of molecularly target agents. Dovitinib, a tyrosine kinase inhibitor targeting both VEGF receptor (VEGFR) and FGFRs, is under clinical investigation in different malignancies including endometrial cancer.
Insights
Novel targeted therapies are being investigated for advanced endometrial cancer due to limited chemotherapy and endocrine therapy efficacy. Bevacizumab shows promise, while FGFR inhibitors like dovitinib offer new therapeutic avenues.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Endocrine therapy and chemotherapy have limited efficacy in advanced, persistent, or recurrent endometrial cancer.
- Previous targeted therapies, including anti-vascular endothelial growth factor (VEGF) agents like sunitinib, sorafenib, and thalidomide, yielded disappointing results.
- Bevacizumab demonstrated promising activity in a phase II study for endometrial cancer.
Purpose of the Study:
- To explore novel molecularly targeted therapies for advanced, persistent, or recurrent endometrial cancer.
- To evaluate the efficacy and toxicity of anti-VEGF agents and novel inhibitors targeting Fibroblast Growth Factor Receptor (FGFR).
Main Methods:
- Review of prior studies on anti-VEGF agents (sunitinib, sorafenib, thalidomide, bevacizumab, aflibercept) in endometrial cancer.
- Analysis of a phase II study involving bevacizumab, assessing progression-free survival by histological type.
- Review of a phase II study of aflibercept in recurrent/persistent endometrial cancer, noting efficacy and toxicity.
- Discussion of FGFR-2 mutations and the development of FGFR inhibitors like dovitinib.
Main Results:
- Bevacizumab showed promising activity, with similar progression-free survival rates for endometrioid (35%) and serous carcinoma (36%) in a small phase II study.
- Aflibercept treatment resulted in 41% of patients being progression-free at 6 months, but 32% discontinued due to toxicity.
- Activating mutations in Fibroblast Growth Factor Receptor (FGFR)-2 have been identified, opening avenues for targeted therapies.
Conclusions:
- Bevacizumab represents a potential targeted therapy for endometrial cancer, though further studies are needed to confirm its efficacy across histological subtypes.
- Toxicity is a concern with some anti-VEGF agents like aflibercept.
- FGFR inhibitors, such as dovitinib, are emerging as promising targeted agents for endometrial cancer, particularly in patients with FGFR mutations.
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