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 (pinteraction = 0.056) revealed that docetaxel-based chemotherapy improved failure-free survival for patients with ERG-positive cancer (HR 0.58; p = 0.03), but not patients with ERG-negative cancer (HR 1.08; p = 0.72). In the ERG-positive subgroup in GETUG 12 (high-risk localized PC), median RFS was 7.79 yr with androgen deprivation therapy (ADT) alone, and was not reached with ADT + docetaxel. In the ERG-negative subgroup, median progression-free survival (mPFS) was 7.79 yr with ADT alone versus 7.08 yr with ADT + docetaxel. In the ERG-positive subgroup in GETUG 15 (metastatic HSPC), mPFS was 10.7 mo with ADT alone versus 18.8 mo with ADT + docetaxel. In the ERG-negative subgroup, mPFS was 10.6 mo with ADT alone versus 13.2 mo with ADT + docetaxel.
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.
European urology oncology. 2024 Jul 20 [Epub ahead of print]
Shanna Rajpar, Tony Ibrahim, Alexandra Carmel, Zahira Merabet, Philippe Vielh, Stephanie Foulon, François Lesaunier, Rémy Delva, Frederic Rolland, Frank Priou, Jean-Marc Ferrero, Nadine Houédé, Loic Mourey, Christine Théodore, Ivan Krakowski, Laura Faivre, Muriel Habibian, Stéphane Culine, Gwenaelle Gravis, Anne Chauchereau, Karim Fizazi
Hôpital Louis Pasteur, Chartres, France., INSERM U981, Prostate Cancer Group, Université Paris-Saclay, Gustave Roussy, Villejuif, France; Department of Medical Oncology, Gustave Roussy, Villejuif, France., Biostatistics Department, Gustave Roussy, Paris-Saclay University, Paris, France., Department of Medical Biology and Pathology, Gustave Roussy, Villejuif, France., Department of Medical Biology and Pathology, Gustave Roussy, Villejuif, France; Medipath and American Hospital of Paris, Paris, France., Department of Radiotherapy, Centre François Baclesse, Caen, France., Institut de Cancerologie de l'Ouest, Angers, France., Department of Medical Oncology, Centre René Gauducheau, Saint-Herblin, France., Department of Medical Oncology, Centre Hospitalier La Roche-sur-Yon, La Roche-sur-Yon, France., Medical Oncology Department, Centre Antoine Lacassagne, University Côte d'Azur, Nice, France., Medical Oncology, Institut de Cancérologie du Gard, Montpellier University, Nimes, France., IUCT-Oncopole, Toulouse, France., Foch Hospital, Suresnes, France., Department of Medical Oncology, Centre Alexis Vautrin, Vandoeuvre Les Nancy, France., R&D UNICANCER, Paris, France., Department of Medical Oncology, Hôpital Saint-Louis, AP-HP, Paris, France., Medical Oncology, Institut Paoli-Calmettes, Marseille, France., INSERM U981, Prostate Cancer Group, Université Paris-Saclay, Gustave Roussy, Villejuif, France., INSERM U981, Prostate Cancer Group, Université Paris-Saclay, Gustave Roussy, Villejuif, France; Department of Medical Oncology, Gustave Roussy, Villejuif, France. Electronic address: .