Fulvestrant for the treatment of endometrial cancer

ABSTRACT

Introduction: About one third of patients with endometrial cancer (EC) relapse and face a limited prognosis, if surgery or radiotherapy are not feasible. The remaining therapeutic options are chemotherapy and endocrine therapy.

Areas covered: This review summarizes the development of the first selective estrogen receptor (ER) down-regulator fulvestrant. This article provides its mechanism of action, pharmacokinetics and the available preclinical and clinical data. Furthermore, this review provides an overview of the market of treatments for recurrent or metastatic EC (RMEC) while also taking into account studies of fulvestrant in metastatic breast cancer.

Expert opinion: Even if fulvestrant showed only marginal activity in two phase II trials, it shouldn’t be abandoned but instead further developed in EC. Firstly, the dose of fulvestrant used in these trials was too low from today’s point of view. Secondly, the available literature on other endocrine agents is full of limitations and does not provide a gold standard. Furthermore, given the activity of mTOR inhibitors in EC, there may also be synergistic effects, given the cross-regulation of ER and the PI3K/AKT/mTOR pathway. The authors suggest that a prospective, phase II trial in ER positive RMEC would help to further explore the efficacy and tolerability of fulvestrant together with a mTOR inhibitor.

KEYWORDS:

• Chemotherapy
• endometrial cancer
• estrogen receptor antagonist
• fulvestrant
• medroxyprogesterone acetate
• megestrol acetate
• mTOR inhibitor
• selective estrogen receptor downregulator
• tamoxifen

Financial and competing interests disclosure

MJ Battista reports personal fees from AstraZeneca, Merck Sharp and Dohme, PharmaMar, and Roche outside of the submitted work. M Schmidt reports grants and personal fees from Pierre-Fabre as well as personal fees and non-financial support from Roche, Amgen Inc and Celgene. He has also received personal fees from Pfizer, Novartis, AstraZeneca, Eisai, and Sividon, outside of the submitted work. M Schmidt also has patents EP2469440 (A3) entitled “Molecular markers for cancer prognosis” and WO2009033941 (A1) entitled “method for predicting the response of a tumor in a patient suffering from or at risk of developing recurrent gynecological cancer towards a chemotherapeutic agent”, pending. He also has patent WO2014118333 (A1) entitled “Method for predicting the benefit from inclusion a taxane in a chemotherapy regimen in patients with BC” also pending. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.