دورية أكاديمية
أعرض في EDS

A correlative biomarker study and integrative prognostic model in chemotherapy-naïve metastatic castration-resistant prostate cancer treated with enzalutamide.

التفاصيل البيبلوغرافية
العنوان: A correlative biomarker study and integrative prognostic model in chemotherapy-naïve metastatic castration-resistant prostate cancer treated with enzalutamide.
المؤلفون: Fernandez-Perez MP; Department of Haematology and Medical Oncology, Hospital Universitario Morales Meseguer, IMIB, Murcia, Spain., Perez-Navarro E; Department of Medical Oncology, Instituto de Investigación, Hospital Universitario 12 de Octubre, Madrid, Spain., Alonso-Gordoa T; Department of Medical Oncology, Hospital Ramón y Cajal, Madrid, Spain., Conteduca V; Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) 'Dino Amadori' IRCCS, Meldola, Italy., Font A; Department of Medical Oncology, Catalan Institute of Oncology, Badalona Applied Research Group in Oncology (BARGO), Badalona, Spain., Vázquez-Estévez S; Department of Medical Oncology, H. Universitario Lucus Augusti, Lugo, Spain., González-Del-Alba A; Department of Medical Oncology, H.U. Son Espases, Palma de Mallorca, Spain., Wetterskog D; University College London Cancer Institute, Paul O'Gorman Building, London, UK., Antonarakis ES; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA., Mellado B; Department of Medical Oncology, IDIBAPS, Hospital Clinic, Universidad de Barcelona, Barcelona, Spain., Fernandez-Calvo O; Department of Medical Oncology, Complejo Hospitalario Universitario Ourense, Orense, Spain., Méndez-Vidal MJ; Department of Medical Oncology, Hospital Universitario Reina Sofía (HURS), Maimonides Institute for biomedical research of Córdoba (IMIBIC), Córdoba, Spain., Climent MA; Servicio de Oncología Médica, Instituto Valenciano de Oncología, Valencia, Spain., Duran I; Instituto de Biomedicina de Sevilla, IBiS/Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Seville, Spain., Gallardo E; Department of Medical Oncology, Servicio de Oncología Médica, Parc Taulí Hospital Universitari, Institut d'Investigació i Innovació Parc Taulí I3PT, Universitat Autònoma de Barcelona, Sabadell, Spain., Rodriguez Sanchez A; Department of Medical Oncology, Hospital Universitario de León, León, Spain., Santander C; Department of Medical Oncology, Hospital Universitario Miguel Servet, Zaragoza, Spain., Sáez MI; Medical Oncology Intercenter Unit, Regional and Virgen de la Victoria University Hospitals, IBIMA, Málaga, Spain., Puente J; Department of Medical Oncology, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), CIBERONC, Madrid, Spain., Tudela J; Department of Pathology, Hospital Morales Meseguer, Murcia, Spain., Martínez A; Biobanco de la región de Murcia, IMIB, Nodo 3, Murcia, Spain., López-Andreo MJ; Department of Molecular Biology, SAI-IMIB-Universidad de Murcia, Murcia, Spain., Padilla J; Department of Haematology and Medical Oncology, Hospital Universitario Morales Meseguer, IMIB, Murcia, Spain., Lozano R; Prostate Cancer Clinical Research Unit, Spanish National Cancer Research Centre, Madrid, Spain.; Genitourinary Translational Research Group, Instituto de Investigación Biomédica de Málaga, Málaga, Spain., Hervas D; Data Science Unit, Instituto de Investigación Sanitaria La Fe, Valencia, Spain., Luo J; Department of Urology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA., de Giorgi U; Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) 'Dino Amadori' IRCCS, Meldola, Italy., Castellano D; Department of Medical Oncology, Instituto de Investigación, Hospital Universitario 12 de Octubre, Madrid, Spain., Attard G; University College London Cancer Institute, Paul O'Gorman Building, London, UK., Grande E; MD Anderson Cancer Center Madrid, Madrid, Spain., Gonzalez-Billalabeitia E; Department of Haematology and Medical Oncology, Hospital Universitario Morales Meseguer, IMIB, Murcia, Spain.; Department of Medical Oncology, Instituto de Investigación, Hospital Universitario 12 de Octubre, Madrid, Spain.; Universidad Católica San Antonio de Murcia-UCAM, Murcia, Spain.
المصدر: The Prostate [Prostate] 2023 Mar; Vol. 83 (4), pp. 376-384. Date of Electronic Publication: 2022 Dec 23.
نوع المنشور: Clinical Trial, Phase II; Journal Article
اللغة: English
بيانات الدورية: Publisher: Wiley-Liss Country of Publication: United States NLM ID: 8101368 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1097-0045 (Electronic) Linking ISSN: 02704137 NLM ISO Abbreviation: Prostate Subsets: MEDLINE
أسماء مطبوعة: Publication: <2005-> : Hoboken, NJ : Wiley-Liss
Original Publication: New York : Alan R. Liss, c1980-
مواضيع طبية MeSH: Neoplastic Cells, Circulating*/pathology , Prostatic Neoplasms, Castration-Resistant*/drug therapy , Prostatic Neoplasms, Castration-Resistant*/genetics , Prostatic Neoplasms, Castration-Resistant*/pathology, Humans ; Male ; Biomarkers, Tumor/genetics ; Nitriles/therapeutic use ; Prognosis ; Prostate-Specific Antigen ; Receptors, Androgen/genetics
مستخلص: Background: There is a considerable need to incorporate biomarkers of resistance to new antiandrogen agents in the management of castration-resistant prostate cancer (CRPC).
Methods: We conducted a phase II trial of enzalutamide in first-line chemo-naïve asymptomatic or minimally symptomatic mCRPC and analyzed the prognostic value of TMPRSS2-ERG and other biomarkers, including circulating tumor cells (CTCs), androgen receptor splice variant (AR-V7) in CTCs and plasma Androgen Receptor copy number gain (AR-gain). These biomarkers were correlated with treatment response and survival outcomes and developed a clinical-molecular prognostic model using penalized cox-proportional hazard model. This model was validated in an independent cohort.
Results: Ninety-eight patients were included. TMPRSS2-ERG fusion gene was detected in 32 patients with no differences observed in efficacy outcomes. CTC detection was associated with worse outcome and AR-V7 in CTCs was associated with increased rate of progression as best response. Plasma AR gain was strongly associated with an adverse outcome, with worse median prostate specific antigen (PSA)-PFS (4.2 vs. 14.7 m; p < 0.0001), rad-PFS (4.5 vs. 27.6 m; p < 0.0001), and OS (12.7 vs. 38.1 m; p < 0.0001). The clinical prognostic model developed in PREVAIL was validated (C-Index 0.70) and the addition of plasma AR (C-Index 0.79; p < 0.001) increased its prognostic ability. We generated a parsimonious model including alkaline phosphatase (ALP); PSA and AR gain (C-index 0.78) that was validated in an independent cohort.
Conclusions: TMPRSS2-ERG detection did not correlate with differential activity of enzalutamide in first-line mCRPC. However, we observed that CTCs and plasma AR gain were the most relevant biomarkers.
(© 2022 The Authors. The Prostate published by Wiley Periodicals LLC.)
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معلومات مُعتمدة: Astellas; PI18/00883 Instituto de Salud Carlos III; SEOM-CRIS Cancer Foundation
فهرسة مساهمة: Keywords: AR gain; AR-V7; CTCs; TMPRSS2-ERG; enzalutamide; prostate cancer
المشرفين على المادة: 0 (Biomarkers, Tumor)
93T0T9GKNU (enzalutamide)
0 (Nitriles)
EC 3.4.21.77 (Prostate-Specific Antigen)
0 (Receptors, Androgen)
EC 3.4.21.- (TMPRSS2 protein, human)
0 (ERG protein, human)
تواريخ الأحداث: Date Created: 20221224 Date Completed: 20230128 Latest Revision: 20230419
رمز التحديث: 20231215
مُعرف محوري في PubMed: PMC10107622
DOI: 10.1002/pros.24469
PMID: 36564933
قاعدة البيانات: MEDLINE
الوصف
تدمد:1097-0045
DOI:10.1002/pros.24469