Medizinonline Medizinonline
  • News
    • News
    • Market & Medicine
  • Patients
    • Disease patterns
    • Diagnostics
    • Therapy
  • Partner Content
    • Dermatology
      • Atopic dermatitis and psoriasis news
      • Dermatology News
    • Diabetes
      • Dia-Month Club – Type 2 Diabetes
      • Diabetes in Motion
      • Diabetes Podcasts
    • Gastroenterology
      • IBD matters
      • Forum Gastroenterology
      • Ozanimod: ulcerative colitis
      • Reflux Update
    • Immunology
      • Primary immunodeficiency – exchange of experience
    • Vaccinate
      • Herpes zoster
    • Infektiologie
    • Neurology
      • EXPERT ULTRASONIC: Introduction to ultrasound-guided injection
      • MS News
      • MS Therapy in Transition
    • Oncology
      • Swiss Oncology in motion
    • Orthopedics
      • Osteoporosis in motion
    • Phytotherapie
    • Practice Management
      • Aargau Cantonal Bank
      • Claraspital
    • Psychiatry
      • Geriatric Psychiatry
    • Rheumatology
  • Departments
    • Allergology and clinical immunology
    • General Internal Medicine
    • Anesthesiology
    • Angiology
    • Surgery
    • Dermatology and venereology
    • Endocrinology and Diabetology
    • Nutrition
    • Gastroenterology and Hepatology
    • Genetics
    • Geriatrics
    • Gynecology
    • Hematology
    • Infectiology
    • Cardiology
    • Nephrology
    • Neurology
    • Emergency and intensive care medicine
    • Nuclear Medicine
    • Oncology
    • Ophthalmology
    • ORL
    • Orthopedics
    • Pediatrics
    • Pharmacology and toxicology
    • Pharmaceutical medicine
    • Phlebology
    • Physical medicine and rehabilitation
    • Pneumology
    • Prevention and health care
    • Psychiatry and psychotherapy
    • Radiology
    • Forensic Medicine
    • Rheumatology
    • Sports Medicine
    • Traumatology and trauma surgery
    • Tropical and travel medicine
    • Urology
    • Dentistry
  • CME & Congresses
    • CME continuing education
    • Congress Reports
    • Congress calendar
  • Practice
    • Noctimed
    • Practice Management
    • Jobs
    • Interviews
  • Log In
  • Register
  • My account
  • Contact
  • English
    • Deutsch
    • Français
    • Italiano
    • Português
    • Español
  • Publications
  • Contact
  • Deutsch
  • English
  • Français
  • Italiano
  • Português
  • Español
Subscribe
Medizinonline Medizinonline
Medizinonline Medizinonline
  • News
    • News
    • Market & Medicine
  • Patienten
    • Krankheitsbilder
    • Diagnostik
    • Therapie
  • Partner Content
    • Dermatology
      • Atopic dermatitis and psoriasis news
      • Dermatology News
    • Diabetes
      • Dia-Month Club – Type 2 Diabetes
      • Diabetes in Motion
      • Diabetes Podcasts
    • Gastroenterology
      • IBD matters
      • Forum Gastroenterology
      • Ozanimod: ulcerative colitis
      • Reflux Update
    • Immunology
      • Primary immunodeficiency – exchange of experience
    • Vaccinate
      • Herpes zoster
    • Infektiologie
    • Neurology
      • EXPERT ULTRASONIC: Introduction to ultrasound-guided injection
      • MS News
      • MS Therapy in Transition
    • Oncology
      • Swiss Oncology in motion
    • Orthopedics
      • Osteoporosis in motion
    • Phytotherapie
    • Practice Management
      • Aargau Cantonal Bank
      • Claraspital
    • Psychiatry
      • Geriatric Psychiatry
    • Rheumatology
  • Departments
    • Fachbereiche 1-13
      • Allergology and clinical immunology
      • General Internal Medicine
      • Anesthesiology
      • Angiology
      • Surgery
      • Dermatology and venereology
      • Endocrinology and Diabetology
      • Nutrition
      • Gastroenterology and Hepatology
      • Genetics
      • Geriatrics
      • Gynecology
      • Hematology
    • Fachbereiche 14-26
      • Infectiology
      • Cardiology
      • Nephrology
      • Neurology
      • Emergency and intensive care medicine
      • Nuclear Medicine
      • Oncology
      • Ophthalmology
      • ORL
      • Orthopedics
      • Pediatrics
      • Pharmacology and toxicology
      • Pharmaceutical medicine
    • Fachbereiche 26-38
      • Phlebology
      • Physical medicine and rehabilitation
      • Phytotherapy
      • Pneumology
      • Prevention and health care
      • Psychiatry and psychotherapy
      • Radiology
      • Forensic Medicine
      • Rheumatology
      • Sports Medicine
      • Traumatology and trauma surgery
      • Tropical and travel medicine
      • Urology
      • Dentistry
  • CME & Congresses
    • CME continuing education
    • Congress Reports
    • Congress calendar
  • Practice
    • Noctimed
    • Practice Management
    • Jobs
    • Interviews
Login

Sie haben noch keinen Account? Registrieren

  • Endometrial Cancer

Prolonged progression-free survival through combination therapy

    • Education
    • General Internal Medicine
    • Gynecology
    • Oncology
    • RX
    • Studies
  • 3 minute read

Endometrial cancer is the sixth most common cancer in women worldwide and has a poor prognosis, particularly in terms of long-term results. The median overall survival time is less than three years. Effective therapy management is particularly indicated for patients with primary advanced or recurrent endometrial cancer. Now study results are raising hopes for a new combination treatment.

Endometrial carcinoma (EC) is a malignant tumor of the uterus originating from the inner mucosal layer of the uterus. The disease predominantly affects post-menopausal women, with a peak age between 65 and 85 years. Early menarche, late menopause, low parity or polycystic ovary syndrome are described as endogenous risk factors. Exogenous risk factors include non-cyclic oestrogen replacement therapy alone, tamoxifen therapy and previous radiotherapy. EC usually involves adenocarcinomas of the uterine lining. Serous and clear cell adenocarcinomas or squamous cell carcinomas occur only rarely. A distinction is made between oestrogen-dependent type I carcinoma and oestrogen-independent type II carcinoma. However, immunohistochemical and molecular markers are also playing an increasingly important role.

Molecular typing enables more precise therapy

Molecular subtyping enables individualized risk stratification and a more precise choice of therapy. As part of The Cancer Genome Atlas (TCGA) project, four molecular subtypes of EC were identified using next generation sequencing (NGS):

  1. POLE: mutated polymerase epsilon (POLE) gene, impaired proofreading function during DNA replication, ultramutated phenotype
  2. MSI-H/dMMR: deficient mismatch repair (dMMR) due to mutations, high microsatellite instability (MSI-H), hypermutated phenotype
  3. Copy number high/TP53abn: high number of somatic copy number alterations, mostly TP53 mutations (TP53 abnormal)
  4. Copy Number low/NSMP: various mutations, no specific molecular profile (NSMP)

Building on this basis, targeted substances (e.g. Dostarlimab, Lenvatinib) have been developed in recent years. MSI-H tumors account for 25-30% of endometrial cancers. The increased expression of programmed cell death receptor 1 (PD-1) and its ligands (PD-L1 and PD-L2) and the high tumor mutational burden associated with dMMR-MSI-H tumors make them potentially susceptible to anti-PD-1 and anti-PD-L1 therapies.

Primary advanced or recurrent EC

Carboplatin plus paclitaxel is the standard chemotherapy for the first-line treatment of primary advanced or recurrent EC. However, the long-term results are still not satisfactory. Before the targeted agents were approved, there were no effective treatment strategies for patients who had failed platinum-based chemotherapy. Dostarlimab is an active immune checkpoint inhibitor that targets the PD-1 receptor. Based on the results of the GARNET study, the drug was approved for dMMR-MSI-H advanced or recurrent endometrial cancer. The researchers have now gone one step further: cytotoxic chemotherapy can have immunomodulatory effects, such as the interruption of immunosuppressive signaling pathways and an enhanced cytotoxic T-cell response. It was therefore reasonable to assume that the combination of chemotherapy and immunotherapy could have a synergistic effect in the tumor microenvironment. The ENGOT-EN-6-NSGO/GOG-3031/RUBY study therefore investigated the efficacy and safety of dostarlimab in combination with carboplatin and paclitaxel compared to placebo plus carboplatin and paclitaxel in patients with primary advanced or recurrent EC.

In the double-blind, multicenter Phase III study, 494 patients (118 of whom had dMMR-MSI-H-EC) were randomized in a 1:1 and received either 500 mg dostarlimab or placebo intravenously in combination with carboplatin and paclitaxel every three weeks for the first six cycles, followed by 1000 mg dostarlimab or placebo intravenously every six weeks for up to three years or until disease progression, discontinuation of treatment due to toxic effects, patient withdrawal, investigator’s decision to withdraw the patient, or death. The primary endpoints were progression-free survival in patients with primary advanced or recurrent dMMR-MSI-H-EC and in the overall population, as well as overall survival in the overall population. Secondary endpoints included progression-free survival determined by a blinded, independent central review, objective response, disease control, duration of response, time to second disease progression, patient-reported outcomes, and pharmacokinetic and immunogenicity analyses.

Prolonged progression-free survival

The overall survival rate after 24 months was 71.3% with dostarlimab and 56.0% with placebo. In the dMMR-MSI-H population, the estimated progression-free survival was 61.4% in the serum group and 15.7% in the placebo group. In the total population, it was 36.1% vs. 18.1%. The most common adverse events were nausea (53.9% versus 45.9%), alopecia (53.5% and 50.0%) and fatigue (51.9% and 54.5%). Patients with primary advanced or recurrent EC were found to benefit significantly from the combination of dostarlimab, carboplatin and paclitaxel in terms of a lower risk of disease progression.

Further reading:

  • Mirza MR, Chase DM, Slomovitz BM, et al.: Dostarlimab for Primary Advanced or Recurrent Endometrial Cancer. N Engl J Med 2023; 388: 2145–2158.
  • www.leitlinienprogramm-onkologie.de/fileadmin/user_upload/LL_Endometriumkarzinom_Langversion_3.01_.pdf (last accessed am 05.01.2024)
  • www.gelbe-liste.de/krankheiten/endometriumkarzinom (last accessed on 05.01.2024)
  • www.krebsgesellschaft.de/onko-internetportal/basis-informationen-krebs/krebsarten/andere-krebsarten/gebaermutterkoerperkrebs.html (last accessed on 05.01.2024).

HAUSARZT PRAXIS 2024; 19(1): 41
InFo ONKOLOGIE & HÄMATOLOGIE 2024; 12(1): 26

Cover picture: Histopathologic representation of endometrioid adenocarcinoma demonstrated in endometrial biopsy. Hematoxylin-eosin stain.
© KGH, wikimedia

Autoren
  • Leoni Burggraf
Publikation
  • HAUSARZT PRAXIS
  • InFo ONKOLOGIE & HÄMATOLOGIE
Related Topics
  • Bendamustine
  • Combination therapy
  • Endometrial Cancer
  • progression-free survival
  • Rituximab
Previous Article
  • ASCO GU Symposium 2024 - locally advanced or metastatic urothelial carcinoma

Strategic therapy sequences to optimize the success of treatment

  • Oncology
  • RX
View Post
Next Article
  • Shared decision making

Participatory decision-making using the example of diets for type 1 diabetes

  • CME continuing education
  • Endocrinology and Diabetology
  • General Internal Medicine
  • Nutrition
  • RX
  • Studies
View Post
You May Also Like
View Post
  • 6 min
  • Case Report

Breast cancer metastases in the bladder

    • Cases
    • Education
    • Gynecology
    • Oncology
    • RX
    • Urology
View Post
  • 11 min
  • Findings from the ALS Symposium 2024 in Montreal

Current and future approaches in the treatment of amyotrophic lateral sclerosis (ALS)

    • Congress Reports
    • Interviews
    • Neurology
    • RX
    • Studies
View Post
  • 8 min
  • Efficacy, mechanism of action and clinical effects

Garlic and high blood pressure

    • Cardiology
    • Education
    • General Internal Medicine
    • Pharmaceutical medicine
    • Phytotherapy
    • RX
    • Studies
View Post
  • 7 min
  • Moderate to severe chronic hand eczema

Delgocitinib cream – first topical pan-JAK inhibitor approved in Switzerland

    • Allergology and clinical immunology
    • Dermatology and venereology
    • Education
    • Infectiology
    • Market & Medicine
    • Pharmacology and toxicology
    • RX
View Post
  • 9 min
  • Wild-type transthyretin amyloid cardiomyopathy (ATTRwt-CA)

Diagnosis at an early stage, prognostic classifications and outlook

    • Cardiology
    • Education
    • RX
    • Studies
View Post
  • 4 min
  • Case report: Drug-induced hepatitis

Rare side effect of tirzepatide therapy

    • Cases
    • Education
    • Endocrinology and Diabetology
    • Gastroenterology and Hepatology
    • Pharmacology and toxicology
    • RX
    • Studies
View Post
  • 4 min
  • Plea for sex-specific neurology

Migraine in men: underdiagnosed, underestimated, under-researched

    • Education
    • Neurology
    • RX
    • Studies
View Post
  • 4 min
  • Prurigo nodularis

Retrospective analyses of large data sets from everyday practice

    • Allergology and clinical immunology
    • Congress Reports
    • Dermatology and venereology
    • RX
Top Partner Content
  • Forum Gastroenterology

    Zum Thema
  • Herpes zoster

    Zum Thema
  • Dermatology News

    Zum Thema
Top CME content
  • 1
    Patience, knowledge and persistence in therapy
  • 2
    Sarcopenia and malnutrition in the context of pneumological rehabilitation
  • 3
    Medical and psychosocial perspectives
  • 4
    New nomenclature for non-alcoholic fatty liver disease
  • 5
    Examinations and considerations before therapy

Newsletter

Sign up and stay up to date

Subscribe
Medizinonline
  • Contact
  • General terms and conditions
  • Imprint

Input your search keywords and press Enter.