OnCo
cancersCancer

Endometrial cancer

The gynaecological cancer where immunotherapy has had the biggest impact, guided by molecular classification.

Endometrial cancer is the most common gynaecologic cancer in high-income countries (~420,000 cases a year worldwide) and one of the few cancers whose incidence and mortality are rising, driven by obesity, diabetes, and an ageing population. Most cases are low-grade endometrioid tumours found at stage I because of postmenopausal bleeding, and are cured by hysterectomy; a minority (serous, clear-cell, carcinosarcoma, and other p53-abnormal tumours) behave like high-grade ovarian cancer and account for most deaths. Since 2013, four molecular classes (POLE-mutated, mismatch-repair deficient, p53-abnormal, no specific molecular profile) have replaced histology as the primary prognostic and predictive framework.

The standard of care for early disease is minimally invasive hysterectomy with sentinel lymph node mapping, and adjuvant therapy scaled to risk: observation or vaginal brachytherapy for low and intermediate risk, pelvic radiotherapy or chemoradiation plus chemotherapy for high risk (PORTEC-3), with molecular class increasingly steering choices and fertility-sparing progestin therapy available for young women with the earliest tumours. Advanced and recurrent disease changed in 2023: three phase 3 trials (RUBY, NRG-GY018, DUO-E) established chemotherapy plus a PD-1/PD-L1 antibody as first-line standard, with dramatic benefit in dMMR tumours and a survival gain in the whole population (RUBY, OS 44.6 vs 28.2 months). Lenvatinib plus pembrolizumab (KEYNOTE-775) remains the second-line option for mismatch-repair-proficient disease, and trastuzumab deruxtecan is approved for HER2 IHC 3+ tumours.

Next: molecular-class-directed adjuvant therapy (RAINBO, PORTEC-4a), folate-receptor and TROP2 ADCs (rinatabart sesutecan with Breakthrough designation, sacituzumab tirumotecan), CDK4/6 plus endocrine therapy for low-grade ER-positive disease, and HER2 ADCs moved earlier in serous cancer. The 2026 failure of selinexor maintenance (XPORT-EC-042) is a caution about subgroup-derived hypotheses. Prevention through weight management and progestin-releasing IUDs, and equitable outcomes for Black women, whose mortality is nearly double, are the population-level problems.

State of the art today

  • IO-chemotherapy first line with OS benefit in dMMR and beyond.
  • Molecular classification (POLE, MMR, p53) is part of routine diagnosis and is beginning to direct adjuvant therapy.
  • Sentinel lymph node mapping has replaced full lymphadenectomy, cutting lymphoedema without missing metastases.
  • HER2 IHC 3+ disease has an approved ADC (T-DXd) with an 85% response rate.
  • Fertility-sparing hormonal therapy is an evidence-based option for the earliest tumours in young women.
Show survival figures (2)

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.

  • Chemotherapy plus PD-1/PD-L1 blockade is first-line standard for advanced disease, with a 16-month overall survival gain in RUBY and a 72% reduction in progression risk in dMMR tumours.
  • Lenvatinib plus pembrolizumab gives an 18-month median survival in pMMR disease after platinum, where PD-1 alone barely worked.
Who it affects
Show survival figures (2)

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.

  • Endometrial cancer accounts for ~420,000 cases and ~97,000 deaths per year worldwide.
  • It is the most common gynaecologic cancer in the US and Europe, with incidence and mortality rising ~1-2% per year.

Where the cases are

Cases by country · GLOBOCAN 2022
All countries →

Site: Corpus uteri. World: 420,368 new cases, 97,723 deaths.

#CountryNew casesDeaths
1China77,72213,511
2United States of America66,05511,939
3Russian Federation29,8526,756
4Japan18,3383,630
5India17,4206,845
6Brazil12,6163,333
7Germany11,7672,531
8United Kingdom10,4402,695
9Italy10,2022,457
10France (metropolitan)9,7602,841

Standard of care

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Early

Hysterectomy; adjuvant therapy by molecular class.

NCCN Guidelines: Uterine Neoplasms
Advanced/recurrent

Chemotherapy + dostarlimab or pembrolizumab; lenvatinib-pembrolizumab; T-DXd if HER2+.

NCCN Guidelines: Uterine Neoplasms
DostarlimabPembrolizumabTrastuzumab deruxtecan
Prevention and hereditary risk

Universal MMR testing of tumours to identify Lynch syndrome; risk-reducing hysterectomy and salpingo-oophorectomy for Lynch carriers after childbearing; levonorgestrel IUD and weight management reduce risk; no screening for average-risk women.

NCCN · 2A
Germline (hereditary) testingMicrosatellite instability (MSI-H) / mismatch repair deficiency (dMMR)Progestins (megestrol acetate, medroxyprogesterone, levonorgestrel IUD)
Diagnosis and staging

Endometrial biopsy for postmenopausal bleeding; MRI for myometrial and cervical invasion; molecular classification (p53, MMR IHC, POLE sequencing) on the diagnostic specimen.

NCCN · 2A
MRIHistopathology & immunohistochemistryEndometrial cancer molecular classes (POLEmut, MMRd, p53abn, NSMP)
Early stage surgery

Minimally invasive total hysterectomy and bilateral salpingo-oophorectomy with sentinel lymph node mapping (FIRES, SENTOR); omentectomy for serous histology.

NCCN · 1
Robotic & minimally invasive surgerySentinel lymph node biopsyFIRES & SENTOR (sentinel node mapping)
Fertility-sparing (grade 1, stage IA, no invasion)

Progestin (oral or IUD) with re-biopsy every 3-6 months; hysterectomy after childbearing.

NCCN · 2B
Fertility-sparing hormonal treatment of early endometrial cancerProgestins (megestrol acetate, medroxyprogesterone, levonorgestrel IUD)
Adjuvant, low and intermediate risk

Observation (low risk, POLEmut) or vaginal brachytherapy (intermediate risk; PORTEC-2); molecular class may de-escalate (PORTEC-4a).

NCCN · 1 (brachytherapy)
BrachytherapyEndometrial cancer molecular classes (POLEmut, MMRd, p53abn, NSMP)
Adjuvant, high risk (stage III, serous, p53abn, deep invasion grade 3)

Chemoradiation plus carboplatin-paclitaxel (PORTEC-3) or chemotherapy alone (GOG-258); pembrolizumab or dostarlimab added for stage III-IV per RUBY/GY018 eligibility.

NCCN · 1
PORTEC-3CarboplatinPaclitaxel / nab-paclitaxelIMRT / IGRT (modern external beam)PembrolizumabDostarlimab
Advanced or recurrent, first line (any MMR status)

Carboplatin-paclitaxel plus dostarlimab (RUBY), pembrolizumab (NRG-GY018/KEYNOTE-868), or durvalumab (DUO-E; dMMR in the US), continued as maintenance up to 2-3 years.

NCCN · 1ESMO-MCBS · 4 (dMMR)
RUBY / ENGOT-EN6 / GOG-3031NRG-GY018 / KEYNOTE-868DUO-E / GOG-3041 / ENGOT-EN10DostarlimabPembrolizumabDurvalumabChemotherapy + PD-1/PD-L1 blockade, first-line advanced endometrial cancer
Recurrent, pMMR, after platinum

Lenvatinib + pembrolizumab (KEYNOTE-775) if not previously given immunotherapy; T-DXd if HER2 IHC 3+; chemotherapy (doxorubicin, weekly paclitaxel); hormonal therapy for low-grade ER-positive disease.

NCCN · 1 (lenvatinib-pembrolizumab)
LenvatinibPembrolizumabKEYNOTE-775 / Study 309Trastuzumab deruxtecanDESTINY-PanTumor02Letrozole (and other aromatase inhibitors)Progestins (megestrol acetate, medroxyprogesterone, levonorgestrel IUD)
Recurrent, dMMR, after chemotherapy

Single-agent PD-1 blockade (dostarlimab GARNET, pembrolizumab) if immunotherapy-naive; otherwise chemotherapy or trials.

NCCN · 1
DostarlimabPembrolizumabMicrosatellite instability (MSI-H) / mismatch repair deficiency (dMMR)
HER2-positive serous

Trastuzumab with carboplatin-paclitaxel (randomised phase 2) or T-DXd for IHC 3+ after prior therapy.

NCCN · 2A
TrastuzumabTrastuzumab deruxtecanHER2DESTINY-PanTumor02

Subtypes & biomarkers

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Subtypes
  • Endometrioid (~80%; grade 1-3; usually ER/PR-positive)
  • Serous (~10%; p53-abnormal; HER2 amplified in ~25-30%)
  • Clear-cell (~3%)
  • Carcinosarcoma (~5%; biphasic; p53-abnormal)
  • Undifferentiated/dedifferentiated (often MMRd, SWI/SNF loss)
  • Molecular classes : POLE-ultramutated (~7%), MMRd (~25-30%), p53-abnormal (~15%), NSMP (~50%)
Biomarkers clinicians test

Target prevalence in this cancer

Target / alterationPrevalenceSource
Estrogen receptor (ERα)
70-80%
Wikipedia
Folate receptor alpha
60-80%
Wikipedia
PIK3CA / PI3K-alpha
45-55%
cBioPortal (TCGA)
WRN helicase (MSI-high cancers)
30%
KRAS
15-20%
cBioPortal (TCGA)
WEE1
n/a
Wikipedia

How common each drug target or alteration is in this cancer. Population-level and approximate; see the target page for detail. Full matrix.

History

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  1. 1971Progestins approved for advanced endometrial cancer
    Progestins (megestrol acetate, medroxyprogesterone, levonorgestrel IUD)
  2. 1983Bokhman's type I / type II model

    Oestrogen-driven low-grade versus non-hormonal high-grade tumours; superseded by molecular classes.

  3. 2009LAP2: laparoscopic hysterectomy equivalent to open surgery
    Robotic & minimally invasive surgery
  4. 2010PORTEC-2: vaginal brachytherapy replaces pelvic radiation for intermediate risk
    Brachytherapy
  5. 2013TCGA molecular classification
  6. 2013TCGA defines four molecular classes

    POLE-ultramutated, MSI-hypermutated, copy-number low, copy-number high (p53-abnormal).

    Endometrial cancer molecular classes (POLEmut, MMRd, p53abn, NSMP)
  7. 2017FIRES: sentinel node mapping validated; pembrolizumab approved for MSI-H tumours
    FIRES & SENTOR (sentinel node mapping)PembrolizumabMicrosatellite instability (MSI-H) / mismatch repair deficiency (dMMR)
  8. 2018PORTEC-3: chemoradiation plus chemotherapy for high-risk disease
    PORTEC-3
  9. 2019Lenvatinib + pembrolizumab accelerated approval (KEYNOTE-146)
    Lenvatinib
  10. 2021KEYNOTE-775: lenvatinib + pembrolizumab OS benefit; dostarlimab approved for dMMR recurrence (GARNET); molecular classification enters ESGO guidelines
    KEYNOTE-775 / Study 309DostarlimabEndometrial cancer molecular classes (POLEmut, MMRd, p53abn, NSMP)
  11. 2023RUBY/NRG-GY018: IO first line
    Dostarlimab
  12. 2023RUBY, NRG-GY018, DUO-E: chemo-immunotherapy first line

    Three trials in one year; dostarlimab approved for dMMR (July 2023).

    RUBY / ENGOT-EN6 / GOG-3031NRG-GY018 / KEYNOTE-868DUO-E / GOG-3041 / ENGOT-EN10
  13. 2024All-comers approvals: pembrolizumab (June), dostarlimab (August), durvalumab dMMR (June); T-DXd tumour-agnostic HER2 approval; RUBY overall survival benefit
    PembrolizumabDostarlimabDurvalumabTrastuzumab deruxtecanDESTINY-PanTumor02
  14. 2025Rina-S Breakthrough designation in endometrial cancer
    Rinatabart sesutecanRAINFOL-01 (Rina-S)
  15. 2026Selinexor maintenance fails (XPORT-EC-042)

    Post-hoc TP53-wild-type subgroup hypothesis not confirmed.

    XPORT-EC-042 / ENGOT-EN20 / GOG-3083Selinexor

Pipeline

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Under reviewADC
Sacituzumab tirumotecan
Phase 2ADC
Puxitatug samrotecan
Phase 3ADC
Rinatabart sesutecan
Phase 3ADC
Luveltamab tazevibulin
ApprovedADC
Trastuzumab deruxtecan · Enhertu
ApprovedSmall-molecule aromatase inhibitor
Letrozole (and other aromatase inhibitors) · Femara; anastrozole (Arimidex); exemestane (Aromasin)
ApprovedSmall-molecule CDK4/6 inhibitor
Abemaciclib · Verzenio
RAINFOL-01 (Rina-S)Molecular-class-directed adjuvant therapy in endometrial cancerHER2 ADCs as standard for HER2-positive serous endometrial cancerWEE1MRD / molecular residual disease testing

Open problems

  • p53-abnormal disease behaves like serous ovarian.
  • Obesity-driven incidence rising.
  • Incidence and mortality are rising, and Black women in the US die at nearly twice the rate of white women, driven by more p53-abnormal tumours and later diagnosis.
  • p53-abnormal and carcinosarcoma histologies still relapse frequently despite chemoradiation; no subtype-specific therapy is approved beyond HER2.
  • Immunotherapy benefit in pMMR disease is modest and biomarkers to select pMMR responders are lacking.
  • Optimal adjuvant strategy by molecular class is unproven prospectively until RAINBO and PORTEC-4a report.
  • Whether radiation adds to chemotherapy in stage III disease remains unresolved (PORTEC-3 vs GOG-258).
  • Fertility-sparing therapy has a 30% relapse rate and no reliable predictor of response.
  • Lenvatinib-pembrolizumab toxicity forces dose reductions in two-thirds of patients.

Trials

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Recruiting now (live from ClinicalTrials.gov)

Recruiting trials near you · live from ClinicalTrials.gov
Endometrial cancer
condition: Endometrial cancer
Open on ClinicalTrials.gov →

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Landmark trials in OnCo

DESTINY-PanTumor02DUO-E / GOG-3041 / ENGOT-EN10FIRES & SENTOR (sentinel node mapping)KEYNOTE-775 / Study 309NRG-GY018 / KEYNOTE-868PORTEC-3RAINFOL-01 (Rina-S)RUBY / ENGOT-EN6 / GOG-3031XPORT-EC-042 / ENGOT-EN20 / GOG-3083

Expert centres

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Where the expertise is

Centres linked to this cancer in OnCo

Seeking a second opinion: ask your oncologist for a referral to a high-volume centre; most accept records and pathology by mail or telehealth. In the US, use the NCI's Find a Cancer Center tool or the nonprofit Cancer Commons, which navigates options for advanced cancers at no cost.

Questions to ask

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Bring to your appointment

Questions to ask your oncologist about Endometrial cancer

Generated from this cancer's standard of care, biomarkers, and pipeline · 34 questions

Newly diagnosed

  1. What is my exact diagnosis, stage, and grade, and which tests established them?
    Why: Everything else follows from an accurate stage and subtype.
  2. Which biomarkers have been tested on my tumour (for example MMR/MSI, POLE, p53, HER2, ER/PR), and what were the results?
    Why: These results decide eligibility for targeted therapy, immunotherapy, and trials.
  3. Which subtype is my cancer, and does that change the recommended treatment?
    Why: Recognised subtypes for this cancer include Endometrioid, Serous, Clear-cell.
  4. Is germline (inherited) genetic testing recommended for me or my family?
    Why: Inherited variants can change treatment and matter for relatives.

Early

  1. For my situation (early), which of the standard options do you recommend and why?
    Why: Guideline options include: Hysterectomy; adjuvant therapy by molecular class.

Advanced/recurrent

  1. For my situation (advanced/recurrent), which of the standard options do you recommend and why?
    Why: Guideline options include: Chemotherapy + dostarlimab or pembrolizumab; lenvatinib-pembrolizumab; T-DXd if HER2+.
  2. Am I a candidate for Dostarlimab, Pembrolizumab, Trastuzumab deruxtecan, and what side effects should I expect?
    Why: Knowing the expected toxicities helps you plan work, family, and supportive care.

Prevention and hereditary risk

  1. For my situation (prevention and hereditary risk), which of the standard options do you recommend and why?
    Why: Guideline options include: Universal MMR testing of tumours to identify Lynch syndrome; risk-reducing hysterectomy and salpingo-oophorectomy for Lynch carriers after childbearing; levonorgestrel IUD and weight management reduce risk; no screening for average-risk women.
  2. Am I a candidate for Progestins (megestrol acetate, medroxyprogesterone, levonorgestrel IUD), and what side effects should I expect?
    Why: Knowing the expected toxicities helps you plan work, family, and supportive care.

Diagnosis and staging

  1. For my situation (diagnosis and staging), which of the standard options do you recommend and why?
    Why: Guideline options include: Endometrial biopsy for postmenopausal bleeding; MRI for myometrial and cervical invasion; molecular classification (p53, MMR IHC, POLE sequencing) on the diagnostic specimen.

Early stage surgery

  1. For my situation (early stage surgery), which of the standard options do you recommend and why?
    Why: Guideline options include: Minimally invasive total hysterectomy and bilateral salpingo-oophorectomy with sentinel lymph node mapping (FIRES, SENTOR); omentectomy for serous histology.
  2. How do the results of FIRES & SENTOR (sentinel node mapping) apply to someone like me?
    Why: Trial populations differ from individual patients; ask how closely you match.

Fertility-sparing (grade 1, stage IA, no invasion)

  1. For my situation (fertility-sparing (grade 1, stage ia, no invasion)), which of the standard options do you recommend and why?
    Why: Guideline options include: Progestin (oral or IUD) with re-biopsy every 3-6 months; hysterectomy after childbearing.
  2. Am I a candidate for Progestins (megestrol acetate, medroxyprogesterone, levonorgestrel IUD), and what side effects should I expect?
    Why: Knowing the expected toxicities helps you plan work, family, and supportive care.

Adjuvant, low and intermediate risk

  1. For my situation (adjuvant, low and intermediate risk), which of the standard options do you recommend and why?
    Why: Guideline options include: Observation (low risk, POLEmut) or vaginal brachytherapy (intermediate risk; PORTEC-2); molecular class may de-escalate (PORTEC-4a).

Adjuvant, high risk (stage III, serous, p53abn, deep invasion grade 3)

  1. For my situation (adjuvant, high risk (stage iii, serous, p53abn, deep invasion grade 3)), which of the standard options do you recommend and why?
    Why: Guideline options include: Chemoradiation plus carboplatin-paclitaxel (PORTEC-3) or chemotherapy alone (GOG-258); pembrolizumab or dostarlimab added for stage III-IV per RUBY/GY018 eligibility.
  2. Am I a candidate for Carboplatin, Paclitaxel / nab-paclitaxel, Pembrolizumab or related drugs, and what side effects should I expect?
    Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
  3. How do the results of PORTEC-3 apply to someone like me?
    Why: Trial populations differ from individual patients; ask how closely you match.

Advanced or recurrent, first line (any MMR status)

  1. For my situation (advanced or recurrent, first line (any mmr status)), which of the standard options do you recommend and why?
    Why: Guideline options include: Carboplatin-paclitaxel plus dostarlimab (RUBY), pembrolizumab (NRG-GY018/KEYNOTE-868), or durvalumab (DUO-E; dMMR in the US), continued as maintenance up to 2-3 years.
  2. Am I a candidate for Dostarlimab, Pembrolizumab, Durvalumab, and what side effects should I expect?
    Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
  3. 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.

Recurrent, pMMR, after platinum

  1. For my situation (recurrent, pmmr, after platinum), which of the standard options do you recommend and why?
    Why: Guideline options include: Lenvatinib + pembrolizumab (KEYNOTE-775) if not previously given immunotherapy; T-DXd if HER2 IHC 3+; chemotherapy (doxorubicin, weekly paclitaxel); hormonal therapy for low-grade ER-positive disease.
  2. 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.
  3. 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.

Recurrent, dMMR, after chemotherapy

  1. For my situation (recurrent, dmmr, after chemotherapy), which of the standard options do you recommend and why?
    Why: Guideline options include: Single-agent PD-1 blockade (dostarlimab GARNET, pembrolizumab) if immunotherapy-naive; otherwise chemotherapy or trials.
  2. 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.

HER2-positive serous

  1. For my situation (her2-positive serous), which of the standard options do you recommend and why?
    Why: Guideline options include: Trastuzumab with carboplatin-paclitaxel (randomised phase 2) or T-DXd for IHC 3+ after prior therapy.
  2. Am I a candidate for Trastuzumab, Trastuzumab deruxtecan, and what side effects should I expect?
    Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
  3. How do the results of DESTINY-PanTumor02 apply to someone like me?
    Why: Trial populations differ from individual patients; ask how closely you match.

Any stage

  1. Are there clinical trials I could join, for example of Sacituzumab tirumotecan, Puxitatug samrotecan, Rinatabart sesutecan, RAINFOL-01 (Rina-S)?
    Why: Trials are how the next standard of care is set; asking early keeps options open.
  2. 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.
  3. 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.
  4. I read that “p53-abnormal disease behaves like serous ovarian”. How does that affect my plan?
    Why: Open problems are where trials and second opinions matter most.
  5. I read that “Obesity-driven incidence rising”. How does that affect my plan?
    Why: Open problems are where trials and second opinions matter most.

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Everything relevant

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Direct links plus the targets, companies, and technologies of this cancer's products.

technologies

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Anti-angiogenic therapyAntibody-drug conjugate (ADC)Bariatric surgery and cancer incidenceBrachytherapyCDK4/6 inhibitorsCoffee and tea intakeCytotoxic chemotherapyEndocrine therapy (SERMs, AIs, SERDs)Fertility-sparing hormonal treatment of early endometrial cancerGermline (hereditary) testingGLP-1 receptor agonists and obesity-related cancer riskHistopathology & immunohistochemistryImmune checkpoint inhibitorsIMRT / IGRT (modern external beam)Monoclonal antibodiesMRD / molecular residual disease testingMRIOncofertility and fertility preservationPlatinum agentsRobotic & minimally invasive surgerySentinel lymph node biopsySite-specific conjugation & linker chemistrySmall-molecule kinase inhibitorsTopoisomerase-I inhibitors (and ADC payloads)

targets

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CDK4/6Claudin 6Estrogen receptor (ERα)FGFR2Folate receptor alphaHER2KITKRASMUC16 (CA-125)PD-1PD-L1PIK3CA / PI3K-alphaRETTP53TROP2VEGF / VEGFRWEE1WRN helicase (MSI-high cancers)

drugs

16
ApprovedSmall-molecule CDK4/6 inhibitor
Abemaciclib · Verzenio
ApprovedCytotoxic chemotherapy (platinum)
Carboplatin
ApprovedMonoclonal antibody (anti-PD-1)
Dostarlimab · Jemperli
ApprovedMonoclonal antibody (anti-PD-L1)
Durvalumab · Imfinzi
ApprovedSmall-molecule multi-kinase inhibitor (VEGFR, FGFR, PDGFR, RET, KIT)
Lenvatinib · Lenvima
ApprovedSmall-molecule aromatase inhibitor
Letrozole (and other aromatase inhibitors) · Femara; anastrozole (Arimidex); exemestane (Aromasin)
Phase 3ADC
Luveltamab tazevibulin
ApprovedCytotoxic chemotherapy (taxane)
Paclitaxel / nab-paclitaxel · Taxol / Abraxane
ApprovedMonoclonal antibody (anti-PD-1)
Pembrolizumab · Keytruda / Keytruda Qlex (SC)
ApprovedHormonal therapy (progestin)
Progestins (megestrol acetate, medroxyprogesterone, levonorgestrel IUD) · Megace; Mirena (IUD)
Phase 2ADC
Puxitatug samrotecan
Phase 3ADC
Rinatabart sesutecan
Under reviewADC
Sacituzumab tirumotecan
ApprovedSmall-molecule XPO1 (nuclear export) inhibitor
Selinexor · Xpovio
ApprovedMonoclonal antibody (anti-HER2)
Trastuzumab · Herceptin (and biosimilars, Phesgo with pertuzumab)
ApprovedADC
Trastuzumab deruxtecan · Enhertu

companies

13
AstraZenecaDaiichi SankyoEisaiEli Lilly (incl. Loxo)GenmabGSKKaryopharm TherapeuticsMerck & Co. (MSD)Mersana TherapeuticsQuanta TherapeuticsRoche / GenentechSichuan Kelun-BiotechSutro Biopharma

institutions

10
ARCAGY-GINECOEuropean Society of Gynaecological OncologyGOG FoundationNorthwell Health Cancer InstituteNRG OncologyPoliclinico Universitario A. GemelliSociety of Gynecologic OncologyStephenson Cancer Center, OU HealthTongji Hospital, Huazhong University of Science and TechnologyTROG Cancer Research

pathways

3
PD-1 / PD-L1 immune checkpoint & T-cell activationPI3K / AKT / mTORWnt / β-catenin

terms

7
Endometrial cancer molecular classes (POLEmut, MMRd, p53abn, NSMP)Glycaemic index and glycaemic loadLynch syndromeMetabolic syndrome and insulin resistanceMicrosatellite instability (MSI-H) / mismatch repair deficiency (dMMR)Obesity-related cancers (IARC list of 13)Tumour-agnostic (tissue-agnostic) approval

trials

9
DESTINY-PanTumor02DUO-E / GOG-3041 / ENGOT-EN10FIRES & SENTOR (sentinel node mapping)KEYNOTE-775 / Study 309NRG-GY018 / KEYNOTE-868PORTEC-3RAINFOL-01 (Rina-S)RUBY / ENGOT-EN6 / GOG-3031XPORT-EC-042 / ENGOT-EN20 / GOG-3083

pairings

3
Chemotherapy + PD-1/PD-L1 blockade, first-line advanced endometrial cancerLenvatinib + pembrolizumab (pMMR endometrial cancer after platinum)PD-1 blockade + VEGF inhibition

ideas

8
A frameshift neoantigen vaccine for Lynch syndrome carriers as the first preventive cancer vaccine approvalA randomised trial of a shared-antigen vaccine to prevent Lynch syndrome cancersA trial of GLP-1 weight-loss drugs with cancer as the primary outcomeGLP-1 drugs to reverse endometrial precancer in women with obesityHER2 ADCs as standard for HER2-positive serous endometrial cancerLink bariatric and GLP-1 registries to cancer registries in every country that has bothMolecular-class-directed adjuvant therapy in endometrial cancerWRN inhibitors: a second synthetic-lethal win for mismatch-repair cancers

people

2
Amit M. OzaGiovanni Scambia

bottlenecks

2
Funding follows fashion, not burdenInherited risk is mostly unidentified

key papers

4
CAPP2: two years of aspirin cuts bowel cancer in Lynch syndrome by more than a third over 10 yearsFirst trial of a vaccine against the shared neoantigens of mismatch-repair-deficient cancersIARC verdict: excess body fat causes 13 cancersRUBY: dostarlimab with chemotherapy for advanced or recurrent endometrial cancer

Key papers

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rctNew England Journal of Medicine 2023changed practice
RUBY: dostarlimab with chemotherapy for advanced or recurrent endometrial cancer

Women with newly diagnosed advanced or recurrent endometrial cancer should receive a PD-1 antibody (dostarlimab or pembrolizumab) with their chemotherapy, and mismatch repair testing is now essential because women with dMMR tumours gain a very large and durable benefit. The gain in mismatch-repair-proficient tumours is real but smaller, and molecular classification (POLE, p53, MMR) is increasingly used to decide who benefits most.

rctThe Lancet 2020changed practice
CAPP2: two years of aspirin cuts bowel cancer in Lynch syndrome by more than a third over 10 years

People with Lynch syndrome should be offered daily aspirin, which roughly halves bowel cancer risk with a delayed and durable effect. Whether a lower dose (as tested in CAPP3) is as effective, and whether the finding extends to the general population, are separate questions.

translationalClinical Cancer Research 2020
First trial of a vaccine against the shared neoantigens of mismatch-repair-deficient cancers

Because Lynch syndrome tumours make the same abnormal proteins in almost every patient, a single vaccine could in principle be given to carriers before cancer develops. This small trial showed the concept is safe and immunogenic; whether it prevents cancer requires the randomised trials now being planned.

reviewNew England Journal of Medicine 2016changed practice
IARC verdict: excess body fat causes 13 cancers

Maintaining a healthy weight is now established cancer prevention for over a dozen cancer types. For clinicians and policymakers, obesity belongs alongside tobacco and alcohol in prevention strategy. Whether intentional weight loss in adulthood reverses risk is still being studied, including in trials of GLP-1 drugs.

Latest papers

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Literature trend1,624 papers in the last 12 months-5% vs prior 12How this is computed
Latest papers · live from Europe PMC
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Query for this cancer: (TITLE:"Endometrial cancer" OR ABSTRACT:"Endometrial cancer") AND (treatment OR therapy OR trial OR survival OR diagnosis). Results are unfiltered search hits about Endometrial cancer, not a curated reading list.

Connected

103top

technologies

16
Anti-angiogenic therapyAntibody-drug conjugate (ADC)Bariatric surgery and cancer incidenceBrachytherapyCoffee and tea intakeFertility-sparing hormonal treatment of early endometrial cancerGermline (hereditary) testingGLP-1 receptor agonists and obesity-related cancer riskHistopathology & immunohistochemistryImmune checkpoint inhibitorsIMRT / IGRT (modern external beam)MRD / molecular residual disease testingMRIOncofertility and fertility preservationRobotic & minimally invasive surgerySentinel lymph node biopsy

targets

14
Claudin 6Estrogen receptor (ERα)Folate receptor alphaHER2KRASMUC16 (CA-125)PD-1PD-L1PIK3CA / PI3K-alphaTP53TROP2VEGF / VEGFRWEE1WRN helicase (MSI-high cancers)

drugs

16
ApprovedSmall-molecule CDK4/6 inhibitor
Abemaciclib · Verzenio
ApprovedCytotoxic chemotherapy (platinum)
Carboplatin
ApprovedMonoclonal antibody (anti-PD-1)
Dostarlimab · Jemperli
ApprovedMonoclonal antibody (anti-PD-L1)
Durvalumab · Imfinzi
ApprovedSmall-molecule multi-kinase inhibitor (VEGFR, FGFR, PDGFR, RET, KIT)
Lenvatinib · Lenvima
ApprovedSmall-molecule aromatase inhibitor
Letrozole (and other aromatase inhibitors) · Femara; anastrozole (Arimidex); exemestane (Aromasin)
Phase 3ADC
Luveltamab tazevibulin
ApprovedCytotoxic chemotherapy (taxane)
Paclitaxel / nab-paclitaxel · Taxol / Abraxane
ApprovedMonoclonal antibody (anti-PD-1)
Pembrolizumab · Keytruda / Keytruda Qlex (SC)
ApprovedHormonal therapy (progestin)
Progestins (megestrol acetate, medroxyprogesterone, levonorgestrel IUD) · Megace; Mirena (IUD)
Phase 2ADC
Puxitatug samrotecan
Phase 3ADC
Rinatabart sesutecan
Under reviewADC
Sacituzumab tirumotecan
ApprovedSmall-molecule XPO1 (nuclear export) inhibitor
Selinexor · Xpovio
ApprovedMonoclonal antibody (anti-HER2)
Trastuzumab · Herceptin (and biosimilars, Phesgo with pertuzumab)
ApprovedADC
Trastuzumab deruxtecan · Enhertu

companies

9
AstraZenecaDaiichi SankyoEisaiGenmabGSKKaryopharm TherapeuticsMerck & Co. (MSD)Mersana TherapeuticsQuanta Therapeutics

institutions

10
ARCAGY-GINECOEuropean Society of Gynaecological OncologyGOG FoundationNorthwell Health Cancer InstituteNRG OncologyPoliclinico Universitario A. GemelliSociety of Gynecologic OncologyStephenson Cancer Center, OU HealthTongji Hospital, Huazhong University of Science and TechnologyTROG Cancer Research

pathways

3
PD-1 / PD-L1 immune checkpoint & T-cell activationPI3K / AKT / mTORWnt / β-catenin

terms

7
Endometrial cancer molecular classes (POLEmut, MMRd, p53abn, NSMP)Glycaemic index and glycaemic loadLynch syndromeMetabolic syndrome and insulin resistanceMicrosatellite instability (MSI-H) / mismatch repair deficiency (dMMR)Obesity-related cancers (IARC list of 13)Tumour-agnostic (tissue-agnostic) approval

trials

9
DESTINY-PanTumor02DUO-E / GOG-3041 / ENGOT-EN10FIRES & SENTOR (sentinel node mapping)KEYNOTE-775 / Study 309NRG-GY018 / KEYNOTE-868PORTEC-3RAINFOL-01 (Rina-S)RUBY / ENGOT-EN6 / GOG-3031XPORT-EC-042 / ENGOT-EN20 / GOG-3083

pairings

3
Chemotherapy + PD-1/PD-L1 blockade, first-line advanced endometrial cancerLenvatinib + pembrolizumab (pMMR endometrial cancer after platinum)PD-1 blockade + VEGF inhibition

ideas

8
A frameshift neoantigen vaccine for Lynch syndrome carriers as the first preventive cancer vaccine approvalA randomised trial of a shared-antigen vaccine to prevent Lynch syndrome cancersA trial of GLP-1 weight-loss drugs with cancer as the primary outcomeGLP-1 drugs to reverse endometrial precancer in women with obesityHER2 ADCs as standard for HER2-positive serous endometrial cancerLink bariatric and GLP-1 registries to cancer registries in every country that has bothMolecular-class-directed adjuvant therapy in endometrial cancerWRN inhibitors: a second synthetic-lethal win for mismatch-repair cancers

people

2
Amit M. OzaGiovanni Scambia

bottlenecks

2
Funding follows fashion, not burdenInherited risk is mostly unidentified

key papers

4
CAPP2: two years of aspirin cuts bowel cancer in Lynch syndrome by more than a third over 10 yearsFirst trial of a vaccine against the shared neoantigens of mismatch-repair-deficient cancersIARC verdict: excess body fat causes 13 cancersRUBY: dostarlimab with chemotherapy for advanced or recurrent endometrial cancer