In recent years, cancer researchers and scientists have learned more about endometrial cancer, especially advanced or recurrent cases. Discoveries about different subtypes of endometrial cancer now help doctors determine the best treatment for each person’s cancer. If you or a loved one are living with endometrial cancer, you may now have access to promising new options.

Understanding the newer treatments now available will help you make informed decisions. This article will cover recent advances in endometrial cancer treatment and five questions to ask your doctor to make sure you get the best care.

New Treatments for Endometrial Cancer

The primary treatment for most people with endometrial cancer is usually surgery. Other treatment options, such as radiation therapy, chemotherapy, or immunotherapy, depend on the stage of your cancer. As cancer researchers learn more about endometrial cancer, more treatments have become available for advanced and recurrent cancer.

1. Immune Checkpoint Inhibitors

Immune checkpoint inhibitors (ICIs) are a type of immunotherapy. These drugs work by blocking a type of protein called checkpoint proteins. Normal cells use checkpoint proteins to prevent the immune system from attacking healthy cells. Some cancer cells also use checkpoint proteins to stop the immune system from identifying and attacking them. By blocking checkpoint proteins, ICIs can help boost your immune response to recognize cancer cells and destroy them, which can slow down or stop cancer growth. These drugs are usually combined with chemotherapy but can also be used on their own.

In 2024, the United States Food and Drug Administration (FDA) approved three ICIs to treat advanced endometrial cancer:

• Dostarlimab-gxly (Jemperli)
• Durvalumab (Imfinzi)
• Pembrolizumab (Keytruda)

You may need additional testing to see if these medications could help treat your cancer.

2. Targeted Therapy

Targeted therapies are drugs that target specific proteins in cancer cells. While several targeted therapies have been used to treat other types of cancer, their use in endometrial cancer is relatively new.

As of 2024, lenvatinib (Lenvima) is the only targeted therapy that’s been approved by the FDA to treat endometrial cancer. Lenvatinib is a type of targeted therapy called a kinase inhibitor. It works by blocking proteins that cancer cells use to grow and form new blood vessels. Lenvatinib is usually used with an immune checkpoint inhibitor, like pembrolizumab.

3. New Uses for Existing Treatments

In addition to new drugs, researchers are also investigating new uses for drugs already used for other conditions. Early research has found that metformin (available as brand names Glucophage, Fortamet, and others) may help to prevent and treat endometrial cancer.

Anti-estrogen drugs are another type of treatment under investigation for endometrial cancer, though they’ve been used for some time to treat the condition. Hormone therapy for endometrial cancer typically involves progestins, such as megestrol, but people with some types of endometrial cancer may also benefit from anti-estrogen drugs.

What To Ask Your Doctor: 5 Questions

With so many new treatments approved and more to come, it can feel overwhelming to understand your treatment options. Asking your doctor the following questions can help you learn more about your cancer and the choices available so you and your cancer care team can decide on the best plan together.

1. Have My Cancer Cells Been Tested for Biomarkers?

Biomarkers are proteins, genes, or molecules that give doctors more information about your cancer. Some new therapies for endometrial cancer are designed to work on cancer cells with specific biomarkers.

Biomarker tests can be done on cancer cells removed during your endometrial biopsy or hysterectomy surgery. Talk to your doctor about the most appropriate tests for your cancer.

2. What Do My Biomarker Results Say About My Prognosis and Treatment Options?

Along with detecting the stage of your cancer, biomarker results can give you more information about your prognosis (outlook) and what treatment options are available.

Biomarkers can tell you and your doctor which genomic subtype of endometrial cancer you have — a category based on specific genetic changes in the cancer cells. Here are the four subtypes:

• DNA polymerase epsilon, catalytic subunit (POLE) mutated
• Microsatellite instability-high (MSI-H) or deficient mismatch repair (dMMR)
• High copy number
• Low copy number

POLE Mutated

Between 5 percent and 10 percent of people with endometrial cancer have mutations (changes) in the POLE gene. They usually have a very good prognosis and rarely experience a recurrence of their cancer.

MSI-H or dMMR Mutations

Around 30 percent of endometrial cancers are considered MSI-H or dMMR. These alterations make cancer cells more susceptible to ICIs. Your doctor may test your tumor for dMMR to find out if these drugs could work for you. However, in 2024, pembrolizumab and dostarlimab were approved by the FDA to treat advanced endometrial cancer in people with or without dMMR.

High or Low Copy Number

Copy number refers to the number of copies of certain genes or pieces of DNA in a cell. Cancers with high copy numbers have extra copies, which can lead to faster growth and a worse prognosis. For example, uterine serous carcinoma, a particularly fast-growing type of endometrial cancer, falls into this category. In contrast, low copy-number cancers don’t have these extra copies or other DNA changes that help cancer grow.

Hormone Receptor Status

Your doctor may also check the hormone receptor status of your cancer cells. They may check for three different hormone receptors — progesterone receptor, estrogen receptor, and human epidermal growth factor-2 (HER2). A meta-analysis (review of past studies) found that higher levels of progesterone and estrogen receptors (hormone receptor-positive) were associated with a better prognosis, while HER2 was associated with a poorer prognosis.

If your endometrial cancer is hormone receptor-positive or HER2-positive, you may have additional treatment options available. Some hormone treatments work best on hormone receptor-positive cancer. Some targeted therapies, such as trastuzumab (Herceptin), or Enhertu, specifically target HER2.

3. How Will My Treatment Be Monitored?

Your health care team will use different tests to monitor you during and after your treatment. Some medications used to treat endometrial cancer may require special tests. You may need regular blood tests and physical exams.

Imaging Tests

You may need imaging tests to check if your cancer has spread to your lymph nodes or other organs and see if it’s responding to treatment. Examples of imaging tests include:

• X-rays
• CT scan
• MRI scan
• Positron emission tomography (PET) scan

If you or your doctor suspects that cancer has spread to your bladder or rectum, they may use a lighted tube to look inside the organ. This procedure is called a cystoscopy when the tube is used to look into your bladder and a proctoscopy when the tube is used to look into your rectum.

Cancer Antigen 125

Some endometrial cancers release a protein called cancer antigen 125 (CA-125) into the bloodstream. In some people, a high CA-125 level might mean that cancer has spread outside of the uterus. If your CA-125 level is high, your doctor may check it periodically to see if it decreases. Typically, CA-125 levels should drop after surgery when the cancer is removed or during your treatment if it is working.

After Treatment

After your treatment is complete, you’ll still have regular follow-up care to check that your cancer hasn’t come back and to check for long-term side effects of your treatment.

4. If My Current Treatment Regimen Isn’t Effective, What Are My Next Options?

If your current treatment isn’t effective, you should find out the next steps. The stage of your cancer is usually the most important factor in choosing the best treatment regimen. If your cancer continues to progress or recurs, your doctor may run many of the same tests you had when you were first diagnosed and restage your cancer. If they haven’t checked already, they may check for biomarkers at this point.

There are many treatment options available for endometrial cancer. It’s a common practice to get a second opinion from a different health care provider about your treatment to confirm the best choice.

5. Would You Recommend I Consider Joining a Clinical Trial?

A clinical trial is a research study that tells how well new treatments and medications work to treat a disease. Before the FDA approves an investigative treatment, it’s available only through a clinical trial.

Your eligibility to participate in a clinical trial may depend on your stage or type of endometrial cancer. Talk to your doctor if you want to learn more about clinical trials.

You can also search for clinical trials on ClinicalTrials.gov, a public government database of clinical trials, or check the National Cancer Institute database of clinical trials.

Talk With Others Who Understand

MyEndometrialCancerTeam is the social network for people with endometrial cancer and their loved ones. On MyEndometrialCancerTeam, members come together to ask questions, give advice, and share their stories with others who understand life with endometrial cancer.

Have you discussed biomarker testing or new treatment options with your doctor? If so, what was most helpful in your conversation? Share your thoughts in the comments below, or start a conversation by posting on your Activities page.