Overview of Endometrial Cancer Treatment Options

Prevalence and Statistics

A recent study published in *Gynecologic Oncology Research and Practice* examines treatment options for endometrial cancer, which constitutes 6% of cancers in women and ranks as the most common gynecologic malignancy in the United States. In 2017, there were approximately 61,380 new cases and an estimated 11,000 deaths attributed to this disease, with both figures rising annually. Obesity is a significant risk factor, contributing to about 50% of cases in Europe and the United States.

Types of Endometrial Adenocarcinoma

Endometrial adenocarcinomas, which are malignant tumors of the uterus, are classified into two types. Type 1 is hormone-mediated, commonly found in obese women producing excess estrogen, and is generally low-grade, often confined to the uterus at diagnosis. Type 2 tumors, which are not estrogen-dependent, typically occur in older, leaner women. Uterine carcinosarcomas represent a more aggressive subgroup, accounting for less than 5% of all uterine cancers.

Current Treatment Landscape

Limited FDA-Approved Options

Currently, there are only two FDA-approved drugs for treating endometrial cancer, highlighting the urgent need for new therapies aimed at advanced, recurrent, and metastatic forms of the disease. The recent review in *Gynecologic Oncology Research and Practice* explores potential new treatment avenues.

Survival Rates and Risk Factors

Most women diagnosed with endometrial cancer do so at an early stage, enjoying a five-year survival rate of 95%. However, those diagnosed at later stages or experiencing a recurrence face significantly poorer outcomes, with only about 17% surviving at the five-year mark. Additional risk factors include rapid endometrial cell growth, the use of tamoxifen, family history, hyperinsulinemia, and reproductive factors like early menarche, late menopause, and polycystic ovarian syndrome. Current treatment for advanced disease often leads to substantial toxicity with limited effectiveness, prompting a search for new therapies, as explored by Makker and colleagues in their study.

Treatment Approaches

Adjuvant Chemotherapy

Doublet chemotherapy is the first-line treatment for advanced endometrial cancer. A study involving 396 patients with stage III or IV endometrial cancer compared five-year survival rates between those receiving doxorubicin-cisplatin chemotherapy and those undergoing abdominal radiation. Results indicated that chemotherapy yielded a significantly higher five-year survival rate of 55%, compared to 42% for radiation, although it was linked to greater toxicity. Another trial evaluated a four-drug chemotherapy regimen (doxorubicin, cisplatin, paclitaxel, and filgrastim) against the doxorubicin-cisplatin combination, finding improved response rates and overall survival, yet also greater neurotoxicity.

Advanced-Disease Treatments

Recent chemotherapy trials for advanced or recurrent disease have not yielded better outcomes compared to single-drug regimens. Specifically, a comparison of ixabepilone with paclitaxel or doxorubicin found no overall survival improvement, leading to the discontinuation of the study.

Hormonal Strategies and Antibody Drug Conjugates

Hormonal therapies targeting hormone receptors have been examined, with megestrol acetate approved over 40 years ago for palliative care in recurrent and metastatic breast and endometrial cancers. In a study of 43 patients receiving zoptarelin doxorubicin, two achieved complete remission and eight showed partial remission. However, a comparison of zoptarelin doxorubicin to doxorubicin alone revealed no significant difference in overall survival. Currently, a study is ongoing for the treatment mirvetuximab soravtansine.

Antiangiogenic Therapies

Bevacizumab therapy targets vascular endothelial growth factor receptors in endometrial cancers, with multiple trials indicating improved progression-free survival. However, similar agents like thalidomide and aflibercept have demonstrated limited efficacy.

Immunotherapy

Recently, the FDA approved pembrolizumab for patients with unresectable or metastatic solid tumors, including endometrial cancers. Ongoing trials are exploring both monotherapy and combinations with paclitaxel and carboplatin.

Conclusion

The rising incidence and mortality rates from endometrial cancer underscore the necessity for clinically proven therapies. A notable decline in clinical trial enrollment due to reduced federal funding presents challenges. Nonetheless, it is vital to design trials that can enhance cancer care and improve outcomes for women facing advanced endometrial cancer.

References

Makker, V., Green, A., Wenham, R., Mutch, D., Davidson, B., & Miller, D. (2017). New therapies for advanced, recurrent, and metastatic endometrial cancers. *Gynecologic Oncology Research And Practice, 4*(1).