Radiotherapy plus Long-term Adjuvant Androgen Deprivation with a Luteinizing Hormone–releasing Hormone Antagonist Versus Agonist in Patients with Very High-risk Localized or Locally Advanced Prostate Cancer: The EORTC GUCG-1414 Phase 3 Randomized Trial
Year: 2025
Type: article
Study design: Clinical Trial
Abstract: BACKGROUND AND OBJECTIVE: External beam radiotherapy (EBRT) combined with long-term androgen deprivation therapy (ADT) is standard for high-risk prostate cancer. EORTC 1414 compared ADT with a luteinizing hormone-releasing hormone (LHRH) antagonist (degarelix) or an LHRH agonist in patients who received EBRT. METHODS: Between 2017 and 2023, 379 patients with prostate cancer with at least two high-risk features (prostate-specific antigen [PSA] ≥20 ng/ml, Gleason score ≥8, cN1, or cT3-4) and stage M0 on conventional imaging or stage M1a/b (n = ≤3 lesions) on advanced imaging were enrolled. Patients were randomized to receive 18, 24, or 36 mo of ADT (degarelix, n = 190; LHRH agonist, n = 189) with pelvic EBRT and treatment of all metastases. Owing to low accrual, the primary endpoint was changed from progression-free survival (PFS) to the PSA nadir response (<0.1 vs ≥0.1 ng/ml) within 6 mo after EBRT. KEY FINDINGS AND LIMITATIONS: Median age was 72 yr. A PSA nadir of <0.1 ng/ml was achieved by 60% of patients in the agonist arm and 52% in the degarelix arm (odds ratio 0.73, 95% confidence interval 0.43-1.22; p = 0.9). Two-year PFS was 88% in both arms. Adverse events occurred in 89% of agonist and 88% of degarelix patients. Among 41 patients with baseline cardiovascular (CV) disease, four in the agonist arm and one in the degarelix group experienced a CV event. Two CV-related deaths occurred in the agonist arm. Degarelix improved lower urinary tract symptoms, particularly in patients with a baseline International Prostate Symptom Score of ≥13. Limitations include early closure and insufficient power to assess PFS. CONCLUSIONS AND CLINICAL IMPLICATIONS: Degarelix did not improve the PSA nadir response within 6 mo after EBRT in comparison to LHRH agonists, but was associated with lower incidence of CV events among patients with pre-existing CV disease.
Source: European Urology Oncology
Authors: Thomas Zilli, Dirk Böhmer, Andreas Roeder, David Lauffer, Ana Elena Villafranca Iturre, Josep Jové Teixidó, Stéphane Supiot, Igor Latorzeff, Piet Dirix, François-Xavier Otte, Giulio Francolini, Thierry Roumeguère, Jean Marc Simon, Beatrice Fournier, Catherine Fortpied, Pedro C. Lara, Bertrand Tombal
Institutions: University of Geneva, Ente Ospedaliero Cantonale, Istituto Oncologico della Svizzera Italiana, Università della Svizzera italiana, Charité - Universitätsmedizin Berlin, University of Copenhagen, Copenhagen University Hospital, Rigshospitalet, University Hospital of Geneva, Complejo Hospitalario de Navarra, Institut Català d'Oncologia, Institut de Cancérologie de l'Ouest, Clinique Pasteur, GZA Ziekenhuizen Campus Sint-Augustinus, GZA Ziekenhuizen, Université Libre de Bruxelles, Institut Jules Bordet, Erasmus Hospital, Azienda Ospedaliero-Universitaria Careggi, University of Florence, Assistance Publique – Hôpitaux de Paris, Pitié-Salpêtrière Hospital, European Organisation for Research and Treatment of Cancer, Universidad Fernando Pessoa Canarias, Cliniques Universitaires Saint-Luc
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $3,790
OpenAlex ID: W4416022800