# Advanced or recurrent endometrial cancer

Source: https://onco.cc/cancers/advanced-recurrent-endometrial-cancer/  
OnCo record `advanced-recurrent-endometrial-cancer` (Cancer). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Summary

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.

## Fields

- Kind: Cancer
- Last checked: 2026-09-17
- Also known as: Stage III to IV endometrial cancer; Metastatic endometrial cancer; Relapsed endometrial cancer; Primary advanced endometrial cancer
- Tags: subtype-page
- Group: gynaecologic
- Burden: 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.
- Subtypes: 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)
- Biomarkers: 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

## Sections of this record

The page is a hub with ten sections in reading order; large sections have their own page. The same plan as JSON: https://onco.cc/api/v1/cancers/advanced-recurrent-endometrial-cancer/sections.json

- Overview (on the hub): The TL;DR, the family this cancer belongs to, the organ, who gets it and what the state of the art is. https://onco.cc/cancers/advanced-recurrent-endometrial-cancer/#overview [3 state-of-the-art points]
- Types and stages (on the hub): Anatomy, the subtypes and how they differ, how it is staged, and where advanced disease spreads. https://onco.cc/cancers/advanced-recurrent-endometrial-cancer/#what-it-is [7 subtypes]
- Symptoms and diagnosis (on the hub): How this cancer shows itself, how the diagnosis is confirmed, and the biomarkers clinicians test for. https://onco.cc/cancers/advanced-recurrent-endometrial-cancer/#finding-it [7 biomarkers]
- Treatment (on the hub): The standard of care by setting, the medicines, surgery and radiotherapy named in it, and the regimens behind them. https://onco.cc/cancers/advanced-recurrent-endometrial-cancer/#treating-it [5 settings, 5 decisions with options]
- Trials and papers (on the hub): Trials recruiting now, the landmark trials, the trials held by this cancer's subtypes, the key papers and what they mean, the latest literature, and the milestones year by year. https://onco.cc/cancers/advanced-recurrent-endometrial-cancer/#evidence [24 trials, 4 key papers, 6 milestones]
- Biology and targets (on the hub): The molecular landscape: the targets and how often each appears, the pathways, the mechanics stages and the preclinical models. https://onco.cc/cancers/advanced-recurrent-endometrial-cancer/#science [13 targets]
- Countries and centres (own page): Cases by country, the UK and NHS pathway and other country lenses, the expert centres with trials on record, and the centres named on this cancer's subtypes. https://onco.cc/cancers/advanced-recurrent-endometrial-cancer/where-you-are/
- Decisions and support (on the hub): The decisions you may face, the aids that walk through them, the warnings on record, the first sixty days and the questions to ask. https://onco.cc/cancers/advanced-recurrent-endometrial-cancer/#living-with-it [21 questions, 6 red cards]
- Pipeline and open problems (own page): Everything in development, the medicines held by this cancer's subtypes, the open problems and what is being done about them, the roadmaps, and what changed on this record. https://onco.cc/cancers/advanced-recurrent-endometrial-cancer/coming/ [16 medicines, 22 trials, 3 open problems]
- Data (own page): Every connected record, the notes, the JSON, Markdown and RDF twins, and where the record came from and when it was checked. https://onco.cc/cancers/advanced-recurrent-endometrial-cancer/data/ [93 connected records]

## Standard of care

- First line, dMMR: Carboplatin-paclitaxel with dostarlimab (RUBY) or pembrolizumab (NRG-GY018), then maintenance immunotherapy for up to three years or two years respectively. ([Dostarlimab](https://onco.cc/drugs/dostarlimab/), [Pembrolizumab](https://onco.cc/drugs/pembrolizumab/), [Carboplatin](https://onco.cc/drugs/carboplatin/), [Paclitaxel / nab-paclitaxel](https://onco.cc/drugs/paclitaxel/), [RUBY / ENGOT-EN6 / GOG-3031](https://onco.cc/trials/ruby/), [NRG-GY018 / KEYNOTE-868](https://onco.cc/trials/nrg-gy018-keynote-868/), [Chemotherapy + PD-1/PD-L1 blockade, first-line advanced endometrial cancer](https://onco.cc/pairings/chemo-io-first-line-endometrial/), [Microsatellite instability (MSI-H) / mismatch repair deficiency (dMMR)](https://onco.cc/terms/msi/))
- First line, pMMR: Carboplatin-paclitaxel with pembrolizumab or dostarlimab, or durvalumab followed by durvalumab-olaparib maintenance (DUO-E); trastuzumab added for HER2-positive serous carcinoma. ([Pembrolizumab](https://onco.cc/drugs/pembrolizumab/), [Dostarlimab](https://onco.cc/drugs/dostarlimab/), [Durvalumab](https://onco.cc/drugs/durvalumab/), [Olaparib](https://onco.cc/drugs/olaparib/), [DUO-E / GOG-3041 / ENGOT-EN10](https://onco.cc/trials/duo-e/), [Trastuzumab](https://onco.cc/drugs/trastuzumab/), [Microsatellite-stable (MSS) / mismatch-repair proficient (pMMR)](https://onco.cc/terms/mss-pmmr/))
- After platinum, pMMR: Lenvatinib with pembrolizumab (KEYNOTE-775); trastuzumab deruxtecan for HER2-expressing tumours; aromatase inhibitors or progestins for low-grade receptor-positive disease. ([Lenvatinib](https://onco.cc/drugs/lenvatinib/), [Pembrolizumab](https://onco.cc/drugs/pembrolizumab/), [KEYNOTE-775 / Study 309](https://onco.cc/trials/keynote-775/), [Trastuzumab deruxtecan](https://onco.cc/drugs/trastuzumab-deruxtecan/), [DESTINY-PanTumor02](https://onco.cc/trials/destiny-pantumor02/), [Letrozole (and other aromatase inhibitors)](https://onco.cc/drugs/letrozole/), [Progestins (megestrol acetate, medroxyprogesterone, levonorgestrel IUD)](https://onco.cc/drugs/megestrol-progestins/))
- After platinum, dMMR without prior immunotherapy: Single-agent dostarlimab or pembrolizumab. ([Dostarlimab](https://onco.cc/drugs/dostarlimab/), [Pembrolizumab](https://onco.cc/drugs/pembrolizumab/), [Immune checkpoint inhibitors](https://onco.cc/technologies/checkpoint-inhibitor/))
- Isolated pelvic recurrence: Radiotherapy with brachytherapy for vaginal recurrence after surgery alone; exenteration in selected central recurrences after radiotherapy. ([IMRT / IGRT (modern external beam)](https://onco.cc/technologies/imrt-igrt/), [Brachytherapy](https://onco.cc/technologies/brachytherapy/), [Radiotherapy](https://onco.cc/terms/radiotherapy/))

## State of the art

- 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.
- 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.

## Open problems

- What to give after progression on first-line immunotherapy.
- The small benefit and real toxicity of immunotherapy in proficient tumours.
- Rising mortality, especially among Black women in the United States, that new drugs have not yet reversed.

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Endometrial_cancer
- Wikipedia: https://en.wikipedia.org/wiki/Endometrial_cancer

## Connected records

- cancers: [Endometrial cancer](https://onco.cc/cancers/endometrial/), [Endometrial cancer with no specific molecular profile](https://onco.cc/cancers/endometrial-nsmp/), [Mismatch-repair-deficient endometrial cancer](https://onco.cc/cancers/endometrial-mmr-deficient/), [p53-abnormal endometrial cancer, including uterine serous carcinoma](https://onco.cc/cancers/endometrial-p53-abnormal/), [POLE-ultramutated endometrial cancer](https://onco.cc/cancers/endometrial-pole-ultramutated/), [Uterine carcinosarcoma](https://onco.cc/cancers/uterine-carcinosarcoma/)
- key papers: [DUO-E: durvalumab with carboplatin-paclitaxel and maintenance durvalumab with or without olaparib in advanced endometrial cancer](https://onco.cc/key-papers/paper-duo-e-jco-2023/), [KEYNOTE-775: lenvatinib plus pembrolizumab versus chemotherapy for previously treated advanced endometrial cancer](https://onco.cc/key-papers/paper-keynote-775-nejm-2022/), [NRG-GY018: pembrolizumab plus chemotherapy in advanced or recurrent endometrial cancer](https://onco.cc/key-papers/paper-nrg-gy018-nejm-2023/), [RUBY: dostarlimab with chemotherapy for advanced or recurrent endometrial cancer](https://onco.cc/key-papers/paper-ruby-nejm-2023/)
- drugs: [Abemaciclib](https://onco.cc/drugs/abemaciclib/), [Carboplatin](https://onco.cc/drugs/carboplatin/), [Dostarlimab](https://onco.cc/drugs/dostarlimab/), [Durvalumab](https://onco.cc/drugs/durvalumab/), [Lenvatinib](https://onco.cc/drugs/lenvatinib/), [Letrozole (and other aromatase inhibitors)](https://onco.cc/drugs/letrozole/), [Luveltamab tazevibulin](https://onco.cc/drugs/luveltamab-tazevibulin/), [Olaparib](https://onco.cc/drugs/olaparib/), [Paclitaxel / nab-paclitaxel](https://onco.cc/drugs/paclitaxel/), [Pembrolizumab](https://onco.cc/drugs/pembrolizumab/), [Progestins (megestrol acetate, medroxyprogesterone, levonorgestrel IUD)](https://onco.cc/drugs/megestrol-progestins/), [Rinatabart sesutecan](https://onco.cc/drugs/rinatabart-sesutecan/), [Sacituzumab tirumotecan](https://onco.cc/drugs/sacituzumab-tirumotecan/), [Saruparib](https://onco.cc/drugs/saruparib/), [Trastuzumab](https://onco.cc/drugs/trastuzumab/), [Trastuzumab deruxtecan](https://onco.cc/drugs/trastuzumab-deruxtecan/)
- trials: [A Clinical Study of the Anti-cancer Effects of an Investigational Therapy or Chemotherapy in Patients With Recurring Uterine Cancer](https://onco.cc/trials/nct06340568/), [A Study of BL-B01D1 + Pembrolizumab ± Bevacizumab in Patients With Recurrent or Metastatic Cervical Cancer and Endometrial Cancer](https://onco.cc/trials/nct07054567/), [A Study of Dostarlimab in Combination With Carboplatin-paclitaxel in Chinese Participants With Primary Advanced or Recurrent Endometrial Cancer (EC)](https://onco.cc/trials/nct07108270/), [A Study of Ixabepilone as Second-line Therapy for Locally Advanced, Recurrent, or Metastatic Endometrial Cancer](https://onco.cc/trials/nct00883116/), [A Study of Lifileucel (Tumor-infiltrating Lymphocytes) in Adults With Advanced Endometrial Cancer.](https://onco.cc/trials/nct06481592/), [A Study to Evaluate the Use of Durvalumab in Combination With Platinum-based Chemotherapy Followed by Durvalumab With Olaparib as First-line Treatment](https://onco.cc/trials/nct06746116/), [DESTINY-Endometrial01: A Phase III Study of Trastuzumab Deruxtecan Plus Rilvegostomig or Pembrolizumab as First-Line Treatment of HER2-Expressing (IHC](https://onco.cc/trials/nct06989112/), [DESTINY-PanTumor02](https://onco.cc/trials/destiny-pantumor02/), [DUO-E / GOG-3041 / ENGOT-EN10](https://onco.cc/trials/duo-e/), [GYNecological Cancers Treated with NETrin MAbs in Combination with Chemotherapy and /or Pembrolizumab](https://onco.cc/trials/nct04652076/), [HS-20089 in Patients With Ovarian Cancer and Endometrial Cancer](https://onco.cc/trials/nct06014190/), [KEYNOTE-775 / Study 309](https://onco.cc/trials/keynote-775/), [NRG-GY018 / KEYNOTE-868](https://onco.cc/trials/nrg-gy018-keynote-868/), [Puxitatug Samrotecan (AZD8205) Monotherapy vs Chemotherapy in B7-H4-selected Endometrial Cancer (Bluestar-Endometrial01)](https://onco.cc/trials/nct07044336/), [RAINFOL-01 (Rina-S)](https://onco.cc/trials/rainfol-01/), [RUBY / ENGOT-EN6 / GOG-3031](https://onco.cc/trials/ruby/), [Sapanisertib and Serabelisib (PIKTOR) With Paclitaxel and a Substudy With an Insulin-Suppressing Diet in Patients With Advanced/Recurrent Endometrial ](https://onco.cc/trials/nct06463028/), [Study of Envafolimab Alone or With Lenvatinib in Patients With Advanced Endometrial Cancer](https://onco.cc/trials/nct05112991/), [Study of Fruquintinib Plus Sintilimab for Treatment of Advanced Endometrial Cancer](https://onco.cc/trials/nct06584032/), [Study of Navtemadlin as Maintenance Therapy in TP53WT Advanced or Recurrent Endometrial Cancer](https://onco.cc/trials/nct05797831/), [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)](https://onco.cc/trials/nct05173987/), [SYD985 in Patients With HER2-expressing Recurrent, Advanced or Metastatic Endometrial Carcinoma](https://onco.cc/trials/nct04205630/), [Trial of Nab-Sirolimus in Combination With Letrozole in Patients With Advanced or Recurrent Endometrioid Endometrial Cancer](https://onco.cc/trials/nct05997017/), [XPORT-EC-042 / ENGOT-EN20 / GOG-3083](https://onco.cc/trials/xport-ec-042/)
- pairings: [Chemotherapy + PD-1/PD-L1 blockade, first-line advanced endometrial cancer](https://onco.cc/pairings/chemo-io-first-line-endometrial/)
- terms: [Microsatellite instability (MSI-H) / mismatch repair deficiency (dMMR)](https://onco.cc/terms/msi/), [Microsatellite-stable (MSS) / mismatch-repair proficient (pMMR)](https://onco.cc/terms/mss-pmmr/), [POLE ultramutation (POLEmut)](https://onco.cc/terms/pole-ultramutation/), [Radiotherapy](https://onco.cc/terms/radiotherapy/)
- technologies: [Brachytherapy](https://onco.cc/technologies/brachytherapy/), [Immune checkpoint inhibitors](https://onco.cc/technologies/checkpoint-inhibitor/), [IMRT / IGRT (modern external beam)](https://onco.cc/technologies/imrt-igrt/)
- people: [Shannon N. Westin](https://onco.cc/people/shannon-westin/), [Vicky Makker](https://onco.cc/people/vicky-makker/)

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JSON: https://onco.cc/api/v1/entities/advanced-recurrent-endometrial-cancer.json