Advanced or recurrent endometrial cancer
Advanced or recurrent endometrial cancer has spread beyond the uterus or come back after treatment. Chemotherapy plus an immune checkpoint antibody is now the first treatment for everyone, with the biggest gains in mismatch-repair-deficient tumours, and lenvatinib with pembrolizumab is the standard when platinum chemotherapy stops working.
Overview
Advanced disease means stage III with nodal or adnexal spread or stage IV with bladder, bowel or distant metastasis, and recurrence after primary treatment behaves in the same way. Treatment begins with surgery where debulking is feasible, then systemic therapy chosen by mismatch-repair status and, increasingly, HER2 and hormone receptor status. Carboplatin-paclitaxel had been the first-line standard since GOG-0209 showed it as effective as and less toxic than the older three-drug regimen, and for pelvic-confined recurrence radiotherapy or exenteration can still be curative.
Three phase 3 trials reported in 2023 changed first-line care. RUBY added dostarlimab to carboplatin-paclitaxel and extended median overall survival in the whole population from 28.2 to 44.6 months, with a hazard ratio of 0.69 and a progression-free survival hazard ratio of 0.28 in mismatch-repair-deficient tumours. NRG-GY018 added pembrolizumab and cut the hazard of progression to 0.30 in deficient and 0.54 in proficient tumours. DUO-E added durvalumab, with a hazard ratio of 0.42 in deficient tumours, and durvalumab plus olaparib maintenance gave 0.57 in proficient tumours. Regulators approved pembrolizumab and dostarlimab with chemotherapy for all comers in 2024, and the gain in proficient disease, though real, is smaller and the subject of debate about cost and toxicity.
After platinum, KEYNOTE-775 established lenvatinib with pembrolizumab, which extended median survival from 11.4 to 18.3 months against doxorubicin or weekly paclitaxel in mismatch-repair-proficient disease, at the price of hypertension, fatigue and diarrhoea that force dose reductions in most patients. Trastuzumab deruxtecan gives responses in HER2-expressing tumours after DESTINY-PanTumor02, endocrine therapy suits low-grade receptor-positive disease, and antibody-drug conjugates against TROP2 and folate receptor alpha (sacituzumab tirumotecan, rinatabart sesutecan) are in phase 3. Maintenance selinexor in TP53-wild-type disease failed in XPORT-EC-042 in 2026, and the sequencing of these agents after first-line immunotherapy is the open clinical question.
State of the art
- KEYNOTE-775 made lenvatinib-pembrolizumab the standard after platinum in proficient disease.
- Antibody-drug conjugates against HER2, TROP2 and folate receptor alpha are the next wave.
Show survival figures (1)
Averages across everyone diagnosed, often years ago. Your stage, subtype, age, fitness and the treatment you receive matter more than the average, and the numbers are improving quickly.
- Chemo-immunotherapy is first-line standard for every advanced endometrial cancer since 2023, with RUBY showing a median survival gain of more than a year overall.
Red cards
From the labels and guidelines behind the standard of care. Your team's thresholds win.- Emergency services nowHypophysitis or adrenal crisis
Persistent headache with extreme tiredness, nausea, dizziness on standing or low blood pressure. Vomiting, severe weakness or collapse is adrenal crisis.
- Emergency services nowBleeding or bruising
Bleeding that will not stop, black or bloody stools, or unexplained bruising when platelets are expected to be low.
- Emergency services nowBlood clot (tamoxifen and others)
A swollen painful calf, or sudden breathlessness with chest pain; the tamoxifen boxed warning covers pulmonary embolism and stroke.
- Emergency services nowBlood clot
A swollen painful calf, or sudden breathlessness with chest pain; venous thromboembolism including pulmonary embolism is a labelled warning.
- Emergency services nowBowel perforation
Sudden severe abdominal pain, a hard or very tender abdomen, or abdominal pain with vomiting and fever. Boxed warning for gastrointestinal perforation on bevacizumab.
- Emergency services nowFainting or palpitations
Fainting, near-fainting, or an irregular or racing heartbeat; several kinase inhibitors prolong the QT interval and the labels require ECG and electrolyte monitoring.
See all on the product pages:CarboplatinDostarlimabDurvalumabLenvatinibLetrozole (and other aromatase inhibitors)OlaparibPaclitaxel / nab-paclitaxelPembrolizumabProgestins (megestrol acetate, medroxyprogesterone, levonorgestrel IUD)·Printable cards in the navigator
Anatomy and lymph node drainage
- Fallopian tube fimbria (origin of high-grade serous)
- Ovary (other histologies, germ cell)
- Endometrium
- Myometrium (uterine sarcoma)
- Placental site (gestational trophoblastic)
- Cervix, transformation zone
- Vulva
- Nodes: obturator and external iliac
- Nodes: internal iliac
- Nodes: para-aortic (ovary, high uterus)
- Nodes: inguinal (vulva)
Most high-grade ovarian cancers begin at the tip of the fallopian tube; endometrial cancer lines the uterus, cervical cancer starts at the transformation zone; each drains to a different node group.
- Fallopian tube fimbria (origin of high-grade serous)HER2-expressing advanced serous carcinoma
- Ovary (other histologies, germ cell)Endometrioid low-grade recurrence (endocrine therapy)
- EndometriumMismatch-repair-proficient, p53-abnormal or NSMP advanced disease · HER2-expressing advanced serous carcinoma · Endometrioid low-grade recurrence (endocrine therapy)
- Myometrium (uterine sarcoma)
- Placental site (gestational trophoblastic)
- Cervix, transformation zoneIsolated vaginal or pelvic recurrence (radiotherapy or surgery with curative intent)
- Vulva
- obturator and external iliac
- internal iliac
- para-aortic (ovary, high uterus)
- inguinal (vulva)
Same organ: High-grade serous ovarian cancer, Low-grade serous ovarian cancer, Clear cell ovarian cancer, Mucinous ovarian cancer, Adult granulosa cell tumour of the ovary, Ovarian cancer, Endometrial cancer, Cervical cancer, Vulvar cancer, Gestational trophoblastic neoplasia, Uterine sarcoma, Vaginal cancer, POLE-ultramutated endometrial cancer, Mismatch-repair-deficient endometrial cancer, p53-abnormal endometrial cancer, including uterine serous carcinoma, Endometrial cancer with no specific molecular profile, Uterine carcinosarcoma, Early cervical cancer and fertility-sparing surgery, Locally advanced cervical cancer, Recurrent or metastatic cervical cancer, Platinum-sensitive ovarian cancer, Platinum-resistant ovarian cancer
Show survival figures (1)
Averages across everyone diagnosed, often years ago. Your stage, subtype, age, fitness and the treatment you receive matter more than the average, and the numbers are improving quickly.
- Around one in five endometrial cancers present at stage III or IV or relapse after treatment; this is the group in which mortality from the disease is rising in many countries, and the group that immunotherapy has transformed since 2023.
Cases by country
No country-level case numbers. This cancer is not mapped to a GLOBOCAN site.
One section per setting: the options named, what each is for, the trials behind them, the recorded trade-offs and the questions to ask.
Carboplatin-paclitaxel with dostarlimab (RUBY) or pembrolizumab (NRG-GY018), then maintenance immunotherapy for up to three years or two years respectively.
Carboplatin-paclitaxel with pembrolizumab or dostarlimab, or durvalumab followed by durvalumab-olaparib maintenance (DUO-E); trastuzumab added for HER2-positive serous carcinoma.
Lenvatinib with pembrolizumab (KEYNOTE-775); trastuzumab deruxtecan for HER2-expressing tumours; aromatase inhibitors or progestins for low-grade receptor-positive disease.
Single-agent dostarlimab or pembrolizumab.
Radiotherapy with brachytherapy for vaginal recurrence after surgery alone; exenteration in selected central recurrences after radiotherapy.
Subtypes & biomarkers
top- Primary stage III to IV endometrial cancer
- First recurrence after surgery with or without adjuvant therapy
- Mismatch-repair-deficient advanced disease (largest immunotherapy benefit)
- Mismatch-repair-proficient, p53-abnormal or NSMP advanced disease
- HER2-expressing advanced serous carcinoma
- Isolated vaginal or pelvic recurrence (radiotherapy or surgery with curative intent)
- Endometrioid low-grade recurrence (endocrine therapy)
- MMR and MSI status (drives the size of immunotherapy benefit)
- p53 and POLE (molecular class)
- HER2 immunohistochemistry (trastuzumab deruxtecan)
- Oestrogen and progesterone receptors (endocrine therapy)
- PD-L1 (not required)
- TROP2 and folate receptor alpha (antibody-drug conjugate trials)
- CA-125 for monitoring
How often this target appears
- 1971Progestins approved for advanced endometrial cancer
- 2012GOG-0209: carboplatin-paclitaxel as effective as and less toxic than TAP
- 2021KEYNOTE-775: lenvatinib-pembrolizumab extends survival after platinum
- 2023RUBY, NRG-GY018 and DUO-E: chemo-immunotherapy first line
- 2024Pembrolizumab and dostarlimab approved with chemotherapy for all comers
- 2026XPORT-EC-042: maintenance selinexor fails in TP53-wild-type disease
Dated changes read from the records linked to this cancer: approvals, regulatory steps, reported trials, guideline versions and milestones. Newest first; no date is inferred.
All 14 changes by month →- 2026-09-17This recordAdvanced or recurrent endometrial cancerFacts on this page last checked
When this page itself was last checked or edited.
- 2026Trial resultXPORT-EC-042 / ENGOT-EN20 / GOG-3083XPORT-EC-042 / ENGOT-EN20 / GOG-3083 reported
Primary PFS endpoint not met; mPFS 12.
- 2026MilestoneXPORT-EC-042 / ENGOT-EN20 / GOG-3083XPORT-EC-042: maintenance selinexor fails in TP53-wild-type disease
A milestone in how this cancer is treated.
- 2025Trial resultRAINFOL-01 (Rina-S)RAINFOL-01 (Rina-S) reported
ORR 55.
- 2024MilestonePembrolizumabPembrolizumab and dostarlimab approved with chemotherapy for all comers
A milestone in how this cancer is treated.
- 2023Trial resultDESTINY-PanTumor02DESTINY-PanTumor02 reported
Endometrial ORR 57.
What is in development for Advanced or recurrent endometrial cancer, drawn from the whole corpus: 12 items. Drugs are grouped by the most advanced trial phase they have reached anywhere; approved treatments sit under standard of care. Technologies are the methods being tested for this cancer, trials are the studies recorded here, and ideas are proposals not yet in a trial.
Drugs in phase 3 · 3
Trials under way · 3
- RAINFOL-01 (Rina-S) · phase 1/2 · Genmab
- DESTINY-Endometrial01: A Phase III Study of Trastuzumab Deruxtecan Plus Rilvegostomig or Pembrolizumab as First-Line Treatment of HER2-Expressing (IHC · phase 3 · AstraZeneca
- Study of Pembrolizumab (MK-3475) Versus Chemotherapy in Mismatch Repair Deficient (dMMR) Advanced or Recurrent Endometrial Carcinoma (MK-3475-C93/KEYNOTE-C93/GOG-3064/ENGOT-en15) · phase 3 · Merck Sharp & Dohme LLC
Trials reported · 5
- DUO-E / GOG-3041 / ENGOT-EN10 · phase 3 · 2023 · positive
- KEYNOTE-775 / Study 309 · phase 3 · 2021 · positive
- NRG-GY018 / KEYNOTE-868 · phase 3 · 2023 · positive
- RUBY / ENGOT-EN6 / GOG-3031 · phase 3 · 2023 · positive
- XPORT-EC-042 / ENGOT-EN20 / GOG-3083 · phase 3 · 2026 · negative
Combinations being explored · 1
Open problems and what is being done
What to give after progression on first-line immunotherapy.
The small benefit and real toxicity of immunotherapy in proficient tumours.
and how the field plans to fix it →What is being done about thisSide effects and quality of lifeAvailable now- Immune checkpoint inhibitorsStandard of care
- IMRT / IGRT (modern external beam)Standard of care
In trialsNothing recorded yet.
Ideas and roadmapsNothing recorded yet.
Also on OnCo: Side effects by symptom · Immune-related side effects · Toxicity compare · Survivorship planner.
Rising mortality, especially among Black women in the United States, that new drugs have not yet reversed.
Trials
topTrials recruiting now
Country and place are remembered in this browser only. A postcode is sent to OpenStreetMap's Nominatim service to find coordinates when you press the button; nothing else leaves your device.
Landmark trials
Expert centres
topExpert centres
New York · cancer center | United States | 0 | 5,100 | 94,456 | #1 | ||
Villejuif · cancer center | France | none recorded | 0 | 1,855 | 31,182 | #6 | |
London · cancer center | United Kingdom | none recorded | 0 | 1,026 | 17,745 | #7 | |
Baltimore · cancer center | United States | 0 | 2,955 | 41,449 | #10 | ||
Tokyo · government | Japan | none recorded | 0 | 1,599 | 21,937 | none recorded | #13 |
Amsterdam · cancer center | Netherlands | none recorded | 0 | 1,451 | 25,873 | #45 | |
Beijing · cancer center | China | none recorded | 0 | 371 | 4,070 | none recorded | #50 |
Philadelphia, PA · consortium | United States | none recorded | 2 | 165 | 1,237 | - | |
Chicago, IL · consortium | United States | none recorded | 2 | not matched | - | - | |
Philadelphia, PA · consortium | United States | none recorded | 1 | 87 | 2,130 | none recorded | - |
Wuhan · hospital | China | none recorded | 0 | 2,478 | 31,527 | - | |
Los Angeles · cancer center | United States | 0 | 2,019 | 32,934 | - | ||
Utrecht · cancer center | Netherlands | none recorded | 0 | 1,422 | 20,323 | - | |
Beijing · cancer center | China | none recorded | 0 | 1,344 | 18,195 | - | |
Leiden · university | Netherlands | none recorded | 0 | 1,245 | 16,125 | - |
These are the things we can measure; they are not a ranking of quality. Each column is a field on the institution record or a count over what OnCo has linked; a centre that treats many patients with Advanced or recurrent endometrial cancer but is thinly recorded here will look small.
Not known: OnCo holds no case-volume or outcome figures for centres, so none are shown. Where a national audit or registry publishes them, the centre's page links to it. Default order: Newsweek rank, then trials for this cancer, then research output.
Questions to ask
topQuestions to ask your oncologist about Advanced or recurrent endometrial cancer
Newly diagnosed
- What is my exact diagnosis, stage, and grade, and which tests established them?Why: Everything else follows from an accurate stage and subtype.
- Which biomarkers have been tested on my tumour (for example MMR and MSI status, p53 and POLE, HER2 immunohistochemistry, Oestrogen and progesterone receptors, PD-L1), and what were the results?Why: These results decide eligibility for targeted therapy, immunotherapy, and trials.
- Which subtype is my cancer, and does that change the recommended treatment?Why: Recognised subtypes for this cancer include Primary stage III to IV endometrial cancer, First recurrence after surgery with or without adjuvant therapy, Mismatch-repair-deficient advanced disease.
- Is germline (inherited) genetic testing recommended for me or my family?Why: Inherited variants can change treatment and matter for relatives.
First line, dMMR
- For my situation (first line, dmmr), which of the standard options do you recommend and why?Why: Guideline options include: Carboplatin-paclitaxel with dostarlimab (RUBY) or pembrolizumab (NRG-GY018), then maintenance immunotherapy for up to three years or two years respectively.
- Am I a candidate for Dostarlimab, Pembrolizumab, Carboplatin or related drugs, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
- How do the results of RUBY / ENGOT-EN6 / GOG-3031 and NRG-GY018 / KEYNOTE-868 apply to someone like me?Why: Trial populations differ from individual patients; ask how closely you match.
First line, pMMR
- For my situation (first line, pmmr), which of the standard options do you recommend and why?Why: Guideline options include: Carboplatin-paclitaxel with pembrolizumab or dostarlimab, or durvalumab followed by durvalumab-olaparib maintenance (DUO-E); trastuzumab added for HER2-positive serous carcinoma.
- Am I a candidate for Pembrolizumab, Dostarlimab, Durvalumab or related drugs, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
- How do the results of DUO-E / GOG-3041 / ENGOT-EN10 apply to someone like me?Why: Trial populations differ from individual patients; ask how closely you match.
After platinum, pMMR
- For my situation (after platinum, pmmr), which of the standard options do you recommend and why?Why: Guideline options include: Lenvatinib with pembrolizumab (KEYNOTE-775); trastuzumab deruxtecan for HER2-expressing tumours; aromatase inhibitors or progestins for low-grade receptor-positive disease.
- Am I a candidate for Lenvatinib, Pembrolizumab, Trastuzumab deruxtecan or related drugs, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
- How do the results of KEYNOTE-775 / Study 309 and DESTINY-PanTumor02 apply to someone like me?Why: Trial populations differ from individual patients; ask how closely you match.
After platinum, dMMR without prior immunotherapy
- For my situation (after platinum, dmmr without prior immunotherapy), which of the standard options do you recommend and why?Why: Guideline options include: Single-agent dostarlimab or pembrolizumab.
- Am I a candidate for Dostarlimab, Pembrolizumab, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
Isolated pelvic recurrence
- For my situation (isolated pelvic recurrence), which of the standard options do you recommend and why?Why: Guideline options include: Radiotherapy with brachytherapy for vaginal recurrence after surgery alone; exenteration in selected central recurrences after radiotherapy.
Any stage
- Are there clinical trials I could join, for example of Sacituzumab tirumotecan, Rinatabart sesutecan, RAINFOL-01 (Rina-S), Trastuzumab deruxtecan?Why: Trials are how the next standard of care is set; asking early keeps options open.
- Would a second opinion at a high-volume centre change anything, and can you help arrange it?Why: Rare or high-stakes decisions benefit from a centre that treats many similar patients.
- What supportive care (symptom control, nutrition, exercise, mental health, financial help) is available from the start?Why: Supportive care improves quality of life and helps patients complete treatment.
- I read that “What to give after progression on first-line immunotherapy”. How does that affect my plan?Why: Open problems are where trials and second opinions matter most.
- I read that “The small benefit and real toxicity of immunotherapy in proficient tumours”. How does that affect my plan?Why: Open problems are where trials and second opinions matter most.
Newly diagnosed? Read the first 60 days with Advanced or recurrent endometrial cancer, then print the one-page appointment sheet with room for the answers.
Print this page for your appointment (your browser's print command). These prompts are for discussion; your clinical team knows your case.
Direct links plus the targets, companies, and technologies of this cancer's products.
technologies
14targets
13drugs
16companies
13terms
3trials
9pairings
1Latest papers
topQuery for this cancer: (TITLE:"Advanced or recurrent endometrial cancer" OR ABSTRACT:"Advanced or recurrent endometrial cancer" OR TITLE:"Stage III to IV endometrial cancer" OR ABSTRACT:"Stage III to IV endometrial cancer" OR TITLE:"Metastatic endometrial cancer" OR ABSTRACT:"Metastatic endometrial cancer" OR TITLE:"Relapsed endometrial cancer" OR ABSTRACT:"Relapsed endometrial cancer" OR TITLE:"Primary advanced endometrial cancer" OR ABSTRACT:"Primary advanced endometrial cancer") AND (treatment OR therapy OR trial OR survival OR diagnosis). Results are unfiltered search hits about Advanced or recurrent endometrial cancer, not a curated reading list.
Similar pages
not linked directly; found by shared links- CancerEndometrial cancer with no specific molecular profile
Shares XPORT-EC-042 / ENGOT-EN20 / GOG-3083, KEYNOTE-775 / Study 309, Progestins (megestrol acetate, medroxyprogesterone, levonorgestrel IUD), Microsatellite-stable (MSS) / mismatch-repair proficient (pMMR) and the tag subtype-page.
- CancerMismatch-repair-deficient endometrial cancer
Shares Study of Pembrolizumab (MK-3475) Versus Chemotherapy in Mismatch Repair Deficient (dMMR) Advanced or Recurrent Endometrial Carcinoma (MK-3475-C93/KEYNOTE-C93/GOG-3064/ENGOT-en15), DUO-E / GOG-3041 / ENGOT-EN10, Chemotherapy + PD-1/PD-L1 blockade, first-line advanced endometrial cancer, NRG-GY018 / KEYNOTE-868 and the tag subtype-page.
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- CancerPOLE-ultramutated endometrial cancer
Shares Dostarlimab, Brachytherapy, Paclitaxel / nab-paclitaxel, Endometrial cancer and the tag subtype-page.
- CancerRecurrent or metastatic cervical cancer
Shares DESTINY-PanTumor02, Sacituzumab tirumotecan, Trastuzumab deruxtecan, Paclitaxel / nab-paclitaxel and the tag subtype-page.
- CancerLocally advanced cervical cancer
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