Promise on the Horizon in Advanced Endometrial Cancer

Alexandra Taylor, MD

Greater knowledge of the molecular changes in advanced endometrial cancer has led researchers to investigate the activity of targeted therapies in this gynecologic landscape, particularly mTOR inhibitors and antiangiogenic agents.

Currently, the standard-of-care therapy for patients with advanced endometrial cancer is chemotherapy, or potentially complete cytoreduction, if eligible.

In a population that has a high rate of comorbidities, it is important to consider the patient’s quality of life during their treatment, said Alexandra Taylor, MD. Unfortunately, patient-reported outcomes and quality-of-life considerations remain an unmet need.

OncLive: What is the current standard treatment for patients with advanced disease?

In an interview with OncLive, Taylor, consultant, clinical oncology, The Royal Marsden Hospital, discussed the advances with targeted therapies in endometrial cancer, as well as the challenges that still exist in the treatment and management of patients with advanced disease.Taylor: Advanced endometrial cancer often covers a range of patients, and about 5% to 10% of patients present with advanced disease. We also have a cohort of patients who also develop recurrent and metastatic disease. Therefore, it is a wide range of presentations; they may be diagnosed after surgery, in terms of having microscopic disease, or they may present with very widespread disease and have a lot of lung or liver metastases at the time of presentation.

The sort of mainstay of treatment is chemotherapy. We need to give systemic treatment, but we also want to consider the different presentations in that, if someone presents with disease that can be surgically removed, we should debate about whether they should have surgery first. Ideally, they have complete cytoreduction, so they undergo surgery and then have chemotherapy.

Are there any treatments currently in development?

We are looking at a diverse group of women. The results with surgery, when the patient undergoes cytoreduction, can be associated with a high risk of complications. We consider the alternative, which is to give neoadjuvant chemotherapy, select those patients who have chemotherapy-sensitive disease, and then [determine whether] complete cytoreduction is then feasible.It is quite an exciting time in the treatment of patients with endometrial cancer. We have a better knowledge of the molecular changes that can guide us toward specific pathways where targeted agents may have activity. We have had a lot of phase II studies looking at single-agent targeted therapies, particularly with the mTOR inhibitors targeting the PI3-kinase pathway, as well as the antiangiogenic agents.

What challenges do you face in managing this particular patient population?

What do you believe is the biggest unmet need in endometrial cancer?

What do you hope that community oncologists understand about the treatment and management of their patients with advanced endometrial cancer?

Is there anything else that you would like to highlight?

The activity has been modest with single agents. We are seeing response rates up to 20% with mTOR inhibitors in chemotherapy-naïve patients, and similarly with the antiangiogenic agents—such as bevacizumab (Avastin)—which demonstrated a response rate of about 13%. As a single agent, there may be limited benefit. However, in the future, we are looking to combine these therapies either with alternative agents or standard chemotherapy. Women with endometrial cancer, as a population, have a high instance of comorbidities. A lot of endometrial cancer is estrogen driven. We know that more than 80% are obese, and there is a high instance of diabetes, cardiovascular disease, arthritis, and poor [renal] function. Therefore, we must individualize treatment for these women, and we must be conscious that our treatment is taking into account the comorbidities and quality of life of our patients. I really need to highlight the lack of quality-of-life and patient-reported outcomes alongside these new potential treatments. At the moment, we have treatments where the survival benefits are very modest; however, the treatment can have a huge impact on a woman's quality of life. We need to work with patients to develop strategies that optimize their quality of life alongside our treatments. There are 2 things. There are exciting treatments coming forward, both in terms of systemic targeted agents and new radiotherapy and surgical techniques. Therefore, I hope that we can look forward to optimizing these [approaches]. The other, bigger message would be the importance of assessing our patients and developing strategies that look to work with patients in terms of quality of life.I am very much interested in looking at the new techniques of management of patients with recurrent disease, especially with local therapies. Again, where we have been concentrating on the management of systemic treatment, we are looking at radiation techniques—specifically stereotactic radiotherapy as a way of significantly improving our local control of recurrent or inoperable disease while minimizing toxicity. We are looking to develop that in new clinical trials.