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Your immune system is your body’s natural defense system, protecting you from infections and diseases. But did you know it also helps fight cancer? If you’re living with advanced endometrial cancer (uterine cancer), your oncologist (cancer doctor) may recommend immunotherapy. This treatment option strengthens your immune system to attack cancer cells and shrink tumors. Recent studies show that immunotherapy can be effective for some types of endometrial cancer, helping people live longer, healthier lives.
In this article, we’ll explain how immunotherapy works and how it’s used to treat endometrial cancer. We’ll also look at how effective it is. With these new treatments, doctors hope to improve outcomes for people with endometrial cancer.
Immunotherapy is a newer type of cancer treatment that boosts the immune system’s ability to fight the disease. Normally, your immune system is on the lookout for abnormal cells, including cancer. Some endometrial cancers produce proteins that let them “hide” from the immune system.
Immune checkpoint inhibitors (ICIs), a type of immunotherapy, block these proteins, preventing cancer cells from hiding. This allows immune cells called T cells to find and destroy tumor cells. Many ICIs target PD-1 and PD-L1. These proteins act like brakes on the immune system, telling it to turn off when it’s not needed.
PD-1 is found on T cells, which help fight cancer and infections. Some endometrial cancer cells take advantage of this by making PD-L1, which latches on to PD-1 and turns off the T cells. This stops the immune system from recognizing and destroying the cancer cells. ICIs work by blocking PD-1 and PD-L1 from connecting so that the T cells can continue fighting the cancer.
You might think that all cancer treatments work the same way, but that’s not true. Traditional chemotherapy targets cells that grow and divide quickly — like cancer cells. However, chemotherapy can’t tell the difference between cancer cells and healthy cells that also grow quickly, such as those in your skin, hair, blood, and the lining of your mouth, intestines, throat, and genitals. That’s why chemotherapy can cause side effects like hair loss, nausea, and mouth sores.
Immunotherapy works differently. Instead of targeting fast-growing cells, it focuses on your immune system and helps your T cells find and destroy cancer cells while leaving healthy cells alone.
The U.S. Food and Drug Administration (FDA) has approved three immunotherapies for endometrial cancer. These treatments include:
Dostarlimab and pembrolizumab are PD-1 inhibitors, and durvalumab is a PD-L1 inhibitor. Oncologists may prescribe these three medications to treat advanced or metastatic endometrial cancer. Advanced cancer means the disease has spread beyond the uterus (stages 3 and 4A), and metastatic cancer (stage 4B) means it has reached other parts of the body, such as the lungs. These medications can also be used to treat recurrent cancer — cancer that returns after previous treatment.
Originally, the FDA approved PD-1 inhibitors for people whose tumors had specific genetic changes that made them more likely to respond to immunotherapy drugs. Your doctor will likely test your tumor for two changes: deficient mismatch repair (dMMR) and high microsatellite instability (MSI-H). Both of these changes make it harder for cells to repair damaged DNA, raising the risk of cancer.
For people with dMMR tumors, durvalumab is often combined with chemotherapy as a first treatment. If the cancer spreads or returns, durvalumab may be used on its own. The FDA recently approved dostarlimab-gxly and pembrolizumab, each paired with chemotherapy, for anyone with advanced endometrial cancer. This means you can qualify for treatment even if your tumor doesn’t test positive for dMMR or MSI-H. Dostarlimab-gxly is also used alone to treat recurrent dMMR endometrial cancer.
Paclitaxel and carboplatin are among the most commonly used chemotherapies. You may be eligible for immunotherapy if your cancer gets worse or grows back after platinum-based chemotherapy such as carboplatin.
Pembrolizumab can be combined with chemotherapy or lenvatinib, a targeted therapy. Oncologists can combine lenvatinib and pembrolizumab to treat recurrent endometrial cancer that is not dMMR or MSI-H. This combination can also be used if your endometrial cancer can’t be treated with radiation or surgery. In some cases, pembrolizumab is given alone.
| Immunotherapy for Endometrial Cancer: How and When It’s Used | |||
| Immunotherapy | How and when it’s given | ||
| With chemotherapy | With lenvatinib | Alone | |
Pembrolizumab | Combined with paclitaxel and carboplatin to treat metastatic or recurrent cancer | For people with cancer that isn’t dMMR or MSI-H, that worsened after previous treatment, and that can’t be cured with surgery or radiation therapy | For people with dMMR or MSI-H cancer whose cancer returned after other treatments and who can’t receive radiation or surgery |
Dostarlimab-gxly | Combined with paclitaxel and carboplatin, followed by dostarlimab-gxly alone, for primary advanced or recurrent endometrial cancer regardless of dMMR/MSI-H status | Not used with lenvatinib | For people with dMMR cancer that worsened or returned after platinum-based chemotherapy |
Durvalumab | Combined with carboplatin plus paclitaxel, followed by single-agent durvalumab, for primary advanced or recurrent dMMR endometrial cancer. | Not used with lenvatinib | Not approved to treat endometrial cancer on its own — used alone as only as maintenance therapy after being combined with chemotherapy |
| References 1. Pembrolizumab — National Cancer Institute | |||
Immunotherapies can come with some side effects, which can vary among the specific drugs. According to the American Cancer Society, side effects generally include:
Immunotherapies are antibody drugs made with biological proteins, and they must be given by IV infusion (delivered into a vein). There’s a small chance that you may have an infusion reaction. Like an allergic reaction, an infusion reaction can cause symptoms such as:
Be sure to tell your cancer care team if you experience any side effects during your treatment.
Cancer researchers test how well new treatments work by conducting clinical trials. These studies compare experimental drugs to standard treatments like chemotherapy. The goal is to improve the survival rate — the percentage of people who are alive after a certain amount of time, such as since diagnosis or after starting a treatment.
Study findings show that combining immunotherapy with chemotherapy improves progression-free survival (PFS). According to the National Cancer Institute, PFS refers to how long you may live before your cancer starts growing again.
In the past few years, some important clinical trials have looked at combining immunotherapy with chemotherapy in endometrial cancer. One trial focused on durvalumab, and another involved pembrolizumab. In both studies, the participants received either the immunotherapy plus chemotherapy or were given chemotherapy alone.
The results showed that people treated with immunotherapy plus chemotherapy had longer PFS — they lived longer without their cancer getting worse. Researchers are still gathering data to better understand how well the combination treatment works.
How well you respond to immunotherapy also depends on your specific tumor. People whose endometrial cancers are dMMR tend to have better responses. However, most endometrial cancer cases aren’t dMMR. People with proficient MMR (pMMR) or dMMR cancers can still respond to immunotherapy treatment — but not as much.
Initially, your oncologist might choose to treat your endometrial cancer with traditional approaches. Examples include:
However, studies show that people with advanced or recurrent endometrial cancer might not respond to these treatments. The survival rate after five years with this type of cancer is less than 20 percent. Immunotherapy offers another option for those who need it most.
Doctors continue to explore how immunotherapy can help treat endometrial cancer. Future studies may combine immunotherapy with targeted therapy to make both treatments work even better.
If you’re interested in learning more about immunotherapy and how it might fit into your treatment plan, talk to your doctor. They can run tests to see if your tumor might respond to these medications. They can also help you weigh the potential benefits and risks of immunotherapy treatment.
On MyEndometrialCancerTeam, the social support network for people with endometrial cancer and their loved ones, members come together to gain a new understanding of endometrial cancer and connect with others who understand life with this condition.
Have you used immunotherapy for endometrial cancer? What was your experience? Share in the comments below or post on your Activities page.
Leonora Valdez Rojas, M.D.
received her medical degree from the Autonomous University of Guadalajara before pursuing a fellowship in internal medicine and subsequently in medical oncology at the National Cancer Institute.
Learn more about her here.
Emily Wagner, M.S.
holds a Master of Science in biomedical sciences with a focus in pharmacology. She is passionate about immunology, cancer biology, and molecular biology.
Learn more about her here.
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