The Benefit of Combining Docetaxel with Androgen Deprivation Therapy in Localized and Metastatic Hormone-sensitive Prostate Cancer is Predicted by ERG Expression: An Analysis of Two GETUG Phase 3 Trials.

Biomarkers Docetaxel ERG Ki67 Prostate cancer

Journal

European urology oncology
ISSN: 2588-9311
Titre abrégé: Eur Urol Oncol
Pays: Netherlands
ID NLM: 101724904

Informations de publication

Date de publication:
20 Jul 2024
Historique:
received: 21 03 2024
revised: 02 06 2024
accepted: 25 06 2024
medline: 22 7 2024
pubmed: 22 7 2024
entrez: 21 7 2024
Statut: aheadofprint

Résumé

Docetaxel has become a standard component of care for advanced prostate cancer (PC); however, its benefits are not universal among patients. A subset of PC cases exhibit TMPRSS2-ERG gene fusion, resulting in ERG overexpression in tumors. Our aim was to assess biomarkers for docetaxel efficacy in men with hormone-sensitive PC (HSPC). Pretreatment prostate biopsies were obtained from participants in two randomized phase 3 clinical trials investigating docetaxel in high-risk localized PC (GETUG 12) and metastatic HSPC (GETUG 15). Immunohistochemistry staining for Ki67, PTEN, RB, and phosphorylated RB was conducted for GETUG 12 samples, and ERG staining for GETUG 12 and GETUG 15 samples. We examined biomarker association with outcomes using univariate and multivariable analyses adjusted for other validated prognostic factors. Among GETUG 12 patients, Ki67 was associated with a worse relapse-free survival (RFS; hazard ratio [HR] 1.72; p = 0.0092). A pooled analysis for the two trials (p Ki67 may serve as a prognostic factor in HSPC, while ERG expression appears to predict a response to docetaxel in both high-risk localized and metastatic HSPC. We assessed factors that could predict outcomes after docetaxel chemotherapy in patients with advanced prostate cancer. We found that expression of a protein called ERG can predict a good response to docetaxel in these patients.

Sections du résumé

BACKGROUND AND OBJECTIVE OBJECTIVE
Docetaxel has become a standard component of care for advanced prostate cancer (PC); however, its benefits are not universal among patients. A subset of PC cases exhibit TMPRSS2-ERG gene fusion, resulting in ERG overexpression in tumors. Our aim was to assess biomarkers for docetaxel efficacy in men with hormone-sensitive PC (HSPC).
METHODS METHODS
Pretreatment prostate biopsies were obtained from participants in two randomized phase 3 clinical trials investigating docetaxel in high-risk localized PC (GETUG 12) and metastatic HSPC (GETUG 15). Immunohistochemistry staining for Ki67, PTEN, RB, and phosphorylated RB was conducted for GETUG 12 samples, and ERG staining for GETUG 12 and GETUG 15 samples. We examined biomarker association with outcomes using univariate and multivariable analyses adjusted for other validated prognostic factors.
KEY FINDINGS AND LIMITATIONS UNASSIGNED
Among GETUG 12 patients, Ki67 was associated with a worse relapse-free survival (RFS; hazard ratio [HR] 1.72; p = 0.0092). A pooled analysis for the two trials (p
CONCLUSIONS AND CLINICAL IMPLICATIONS CONCLUSIONS
Ki67 may serve as a prognostic factor in HSPC, while ERG expression appears to predict a response to docetaxel in both high-risk localized and metastatic HSPC.
PATIENT SUMMARY RESULTS
We assessed factors that could predict outcomes after docetaxel chemotherapy in patients with advanced prostate cancer. We found that expression of a protein called ERG can predict a good response to docetaxel in these patients.

Identifiants

pubmed: 39034169
pii: S2588-9311(24)00173-1
doi: 10.1016/j.euo.2024.06.015
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

Copyright © 2024 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Auteurs

Shanna Rajpar (S)

Hôpital Louis Pasteur, Chartres, France.

Tony Ibrahim (T)

INSERM U981, Prostate Cancer Group, Université Paris-Saclay, Gustave Roussy, Villejuif, France; Department of Medical Oncology, Gustave Roussy, Villejuif, France.

Alexandra Carmel (A)

Biostatistics Department, Gustave Roussy, Paris-Saclay University, Paris, France.

Zahira Merabet (Z)

Department of Medical Biology and Pathology, Gustave Roussy, Villejuif, France.

Philippe Vielh (P)

Department of Medical Biology and Pathology, Gustave Roussy, Villejuif, France; Medipath and American Hospital of Paris, Paris, France.

Stephanie Foulon (S)

Biostatistics Department, Gustave Roussy, Paris-Saclay University, Paris, France.

François Lesaunier (F)

Department of Radiotherapy, Centre François Baclesse, Caen, France.

Rémy Delva (R)

Institut de Cancerologie de l'Ouest, Angers, France.

Frederic Rolland (F)

Department of Medical Oncology, Centre René Gauducheau, Saint-Herblin, France.

Frank Priou (F)

Department of Medical Oncology, Centre Hospitalier La Roche-sur-Yon, La Roche-sur-Yon, France.

Jean-Marc Ferrero (JM)

Medical Oncology Department, Centre Antoine Lacassagne, University Côte d'Azur, Nice, France.

Nadine Houédé (N)

Medical Oncology, Institut de Cancérologie du Gard, Montpellier University, Nimes, France.

Loic Mourey (L)

IUCT-Oncopole, Toulouse, France.

Christine Théodore (C)

Foch Hospital, Suresnes, France.

Ivan Krakowski (I)

Department of Medical Oncology, Centre Alexis Vautrin, Vandoeuvre Les Nancy, France.

Laura Faivre (L)

Biostatistics Department, Gustave Roussy, Paris-Saclay University, Paris, France.

Muriel Habibian (M)

R&D UNICANCER, Paris, France.

Stéphane Culine (S)

Department of Medical Oncology, Hôpital Saint-Louis, AP-HP, Paris, France.

Gwenaelle Gravis (G)

Medical Oncology, Institut Paoli-Calmettes, Marseille, France.

Anne Chauchereau (A)

INSERM U981, Prostate Cancer Group, Université Paris-Saclay, Gustave Roussy, Villejuif, France.

Karim Fizazi (K)

INSERM U981, Prostate Cancer Group, Université Paris-Saclay, Gustave Roussy, Villejuif, France; Department of Medical Oncology, Gustave Roussy, Villejuif, France. Electronic address: karim.fizazi@gustaveroussy.fr.

Classifications MeSH