New endometrial cancer treatments and longer-term clinical trial results are changing how advanced and recurrent endometrial cancer is treated. One of the biggest advances has been adding immunotherapy to frontline chemotherapy, which can help some patients remain progression-free for significantly longer.
Treatment is also becoming increasingly personalized. Doctors can test tumors for biomarkers such as mismatch repair (MMR) status, microsatellite instability (MSI), HER2, hormone receptors, and other molecular features. These results can help determine which treatments may be most effective for an individual patient's cancer.
About 25% to 30% of endometrial cancers have deficient mismatch repair (dMMR). These tumors have become particularly important in endometrial cancer research because they can be highly responsive to immune checkpoint inhibitors.
THE BASICS: Major 2026 endometrial cancer advances include longer-term evidence supporting immunotherapy plus chemotherapy for advanced and recurrent disease and continued research into targeted therapies and antibody-drug conjugates. Molecular testing is playing an increasingly important role in matching patients with treatment.
Why is immunotherapy changing endometrial cancer treatment?
Immunotherapy helps the body's immune system recognize and attack endometrial cancer cells. One important type of immunotherapy is an immune checkpoint inhibitor, which blocks signals cancer cells can use to avoid an immune attack.
Checkpoint inhibitors including dostarlimab (Jemperli), pembrolizumab (Keytruda), and durvalumab (Imfinzi) have changed treatment for advanced and recurrent endometrial cancer.
The benefit can be particularly large in cancers that are dMMR or microsatellite instability-high (MSI-H). However, some immunotherapy-based approaches are also approved for broader groups of patients.
These advances highlight why testing a tumor's molecular profile is becoming an essential part of treatment planning in gynecologic oncology.
What did the RUBY trial show about immunotherapy and chemotherapy?
The international Phase 3 RUBY trial (NCT03981796) evaluated dostarlimab plus standard chemotherapy drugs carboplatin and paclitaxel in patients with primary advanced or recurrent endometrial cancer.
Patients received dostarlimab or placebo with chemotherapy, followed by maintenance dostarlimab or placebo.
Earlier results showed that adding dostarlimab significantly improved progression-free survival, with particularly strong results among patients whose tumors were dMMR/MSI-H. These findings helped lead to FDA approval of dostarlimab with carboplatin and paclitaxel, followed by dostarlimab alone, for adults with primary advanced or recurrent endometrial cancer.
Longer-term data presented in 2026 provided additional information about how durable this benefit may be.
What did the 2026 RUBY results show for dMMR patients?
With at least four years of follow-up, 57.9% of patients with dMMR/MSI-H tumors who received dostarlimab plus chemotherapy remained alive without cancer progression at four years, compared with 15.7% of patients who received chemotherapy alone.
Only four additional progression-free survival events occurred during approximately 2.5 additional years of follow-up, suggesting that disease control was durable for many patients.
Researchers also used a statistical model to explore the potential for long-term disease control. The model estimated that 54% of patients receiving dostarlimab plus chemotherapy could have "curative potential." This is a modeling estimate—not evidence that 54% of patients have definitively been cured—and longer follow-up remains important.
Overall, the findings strengthen the evidence that adding immunotherapy to chemotherapy can produce long-lasting benefits for some patients with dMMR/MSI-H advanced or recurrent endometrial cancer.
What did the NRG-GY018 trial show for endometrial cancer patients?
The Phase 3 NRG-GY018 trial, also called KEYNOTE-868 (NCT03914612), evaluated pembrolizumab plus carboplatin and paclitaxel for patients with advanced or recurrent endometrial cancer.
Researchers separated patients based on MMR status into dMMR and mismatch repair-proficient (pMMR) groups.
The study demonstrated a significant improvement in progression-free survival when pembrolizumab was added to chemotherapy in both groups. In the dMMR group, the risk of disease progression or death was substantially lower with pembrolizumab plus chemotherapy. The pMMR group also experienced a meaningful improvement. These results helped establish pembrolizumab plus chemotherapy followed by pembrolizumab as an important first-line treatment option for primary advanced or recurrent endometrial carcinoma.
The FDA approved this combination in 2024 for adults with primary advanced or recurrent endometrial carcinoma regardless of MMR status.
Why are biomarkers important for endometrial cancer treatment?
Endometrial cancer is no longer treated as though every tumor has the same biology. Biomarkers can reveal important differences between cancers that may look similar under a microscope.
Testing may include MMR proteins or MSI status, HER2, hormone receptors, p53, POLE mutations, and other molecular characteristics depending on the patient's disease and treatment setting.
Research involving the cancer genome has helped scientists identify molecular subgroups of endometrial cancer with different biology and prognosis. These findings are increasingly influencing clinical research and therapeutic strategies.
For example, dMMR/MSI-H cancers can be particularly responsive to checkpoint immunotherapy. HER2 overexpression is more common in certain aggressive endometrial cancer types, including some uterine serous cancers, and can create opportunities for HER2-directed treatment.
What targeted therapy options are emerging for endometrial cancer?
Targeted therapy attacks specific proteins or pathways that help cancer grow. Unlike traditional chemotherapy, targeted treatments are designed around particular characteristics of the cancer.
One established approach for certain patients with previously treated advanced endometrial cancer is pembrolizumab plus lenvatinib (Lenvima). Lenvatinib is a kinase inhibitor that affects pathways involved in tumor growth and blood vessel formation.
Anti-angiogenic treatments interfere with a tumor's ability to develop new blood vessels. Bevacizumab, another medication that targets blood vessel growth, has also been studied in endometrial cancer, although its role differs from approved frontline immunotherapy regimens.
Researchers continue to evaluate these and other innovative therapies to determine which patients are most likely to benefit.
How are antibody-drug conjugates targeting cancer cells?
Antibody-drug conjugates, or ADCs, are another important area of research. These treatments combine an antibody designed to recognize a specific target on cancer cells with a powerful anticancer drug.
The goal is to deliver treatment more directly to cancer cells while limiting exposure to healthy tissue.
Several targets are being investigated in endometrial cancer and other solid tumors, including HER2, TROP-2, and folate receptor alpha.
Trastuzumab deruxtecan (T-DXd) targets HER2 and has generated interest across multiple HER2-expressing cancers. HER2-directed strategies may be particularly relevant for some aggressive endometrial cancers, including serous carcinoma.
Sacituzumab govitecan targets TROP-2, while other ADCs are being investigated against additional molecular targets. Their exact role in routine endometrial cancer care continues to evolve as clinical trial results become available.
What role do surgery and radiation therapy have in endometrial cancer?
Although much of the recent research has focused on systemic treatments, surgery remains central to treatment for many people with newly diagnosed endometrial cancer.
Endometrial cancer begins in the lining of the uterus. Surgery commonly includes removal of the uterus, called a hysterectomy, along with the fallopian tubes and ovaries. Lymph node assessment may also be performed depending on the patient's cancer and surgical plan.
An endometrial biopsy is commonly used before treatment to diagnose the cancer and determine its histologic type and grade.
Radiation therapy also remains important for selected patients. Depending on recurrence risk, stage, and tumor characteristics, radiation may be used after surgery or to treat locally advanced or recurrent disease.
These established treatments remain important even as immunotherapy and targeted treatment expand the options available to patients.
Are chemotherapy and hormone therapy still used for uterine cancer?
Yes. Carboplatin and paclitaxel remain important chemotherapy drugs for advanced and recurrent uterine cancer, including endometrial cancer.
For some patients, chemotherapy is now combined with immunotherapy rather than given alone. The appropriate approach depends on disease stage, previous treatment, tumor characteristics, and overall health.
Hormone therapy can also be useful for selected endometrial cancers, particularly tumors that express estrogen or progesterone receptors and have features suggesting they may respond to hormonal treatment. Options can include progestins and other hormone-directed medications.
These treatments demonstrate why there is no single best treatment for every patient. Endometrial cancer includes multiple biologic subtypes that can respond differently to therapy.
How does endometrial cancer research compare with other gynecologic cancers?
Endometrial cancer is one of several gynecologic cancers, along with ovarian cancer, cervical cancer, vaginal cancer, and vulvar cancer.
These cancers develop in different organs and should not be treated as though they are the same disease. For example, cervical cancer begins in the cervix, while ovarian cancer begins in or involves the ovaries, fallopian tubes, or peritoneum depending on the cancer type.
However, research across gynecologic cancers can sometimes reveal treatment strategies that warrant study in multiple diseases. Immunotherapies, ADCs, anti-angiogenic therapies, and biomarker-directed treatments are examples of approaches being investigated across several cancer types.
What other treatment options are being studied?
Researchers continue to investigate other treatment options for patients with advanced cancers, particularly when standard therapies stop working.
Clinical trials are evaluating new immunotherapy combinations, targeted agents, ADCs, hormone-based approaches, and treatments selected according to specific tumor biomarkers.
Researchers are also trying to determine the best sequence for these treatments. As more effective therapies become available, an increasingly important question is not simply which drug works, but which treatment should be used first and what should follow if the cancer progresses.
Some studies are also evaluating whether particular treatments can be moved into earlier stages of disease or combined with surgery or radiation.
What do the 2026 advances mean for endometrial cancer treatment?
The biggest change in endometrial cancer care is the shift toward more personalized treatment. Instead of basing therapy only on stage and what cancer cells look like under a microscope, doctors can increasingly incorporate molecular information when choosing treatment.
Long-term results from trials such as RUBY provide encouraging evidence that immunotherapy plus chemotherapy can produce durable disease control for some patients, especially those with dMMR/MSI-H tumors. The FDA has also approved pembrolizumab plus chemotherapy and dostarlimab plus chemotherapy for broader populations with primary advanced or recurrent disease. Durvalumab plus chemotherapy is approved for dMMR primary advanced or recurrent endometrial cancer.
At the same time, targeted treatments, antibody-drug conjugates, hormone therapy, surgery, radiation therapy, and other treatments remain important parts of care.
The rapid pace of endometrial cancer research means patients with advanced or recurrent disease may have more options than were available only a few years ago. Biomarker testing and discussion of clinical trials can help patients and their healthcare teams identify treatments that fit the individual characteristics of their cancer.
For patients, the most important question is how these advances apply to their specific diagnosis. Ask your gynecologic oncology team about your tumor's MMR/MSI status, molecular profile, available standard treatments, and whether a clinical trial could provide another option.
