المؤلفون: Fernandez-Perez, Maria P, Perez-Navarro, Enrique, Alonso-Gordoa, Teresa, Conteduca, Vicenza, Font, Albert, Vazquez-Estevez, Sergio, Gonzalez-del-Alba, Aranzazu, Wetterskog, Daniel, Antonarakis, Emmanuel S, Mellado, Begona, Fernandez-Calvo, Ovidio, Mendez-Vidal, Maria J, Climent, Miguel A, Duran, Ignacio, Gallardo, Enrique, Rodriguez Sanchez, Angel, Santander, Carmen, Saez, Maria, Puente, Javier, Tudela, Julian, Martinez, Alberto, Lopez-Andreo, Maria J, Padilla, Jose, Lozano, Rebeca, Hervas, David, Luo, Jun, de Giorgi, Ugo, Castellano, Daniel, Attard, Gerhardt, Grande, Enrique, Gonzalez-Billalabeitia, Enrique

المصدر: Prostate , 83 (4) pp. 376-384. (2023)

مصطلحات موضوعية: Science & Technology, Life Sciences & Biomedicine, Endocrinology & Metabolism, Urology & Nephrology, AR gain, AR-V7, CTCs, enzalutamide, prostate cancer, TMPRSS2-ERG, CIRCULATING TUMOR-CELLS, GENE STATUS, ANDROGEN RECEPTOR, CLINICAL-TRIALS, ABIRATERONE, SURVIVAL, SURROGATE, TMPRSS2, FUSION, MEN

الوصف: 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.

وصف الملف: text

العلاقة: https://discovery.ucl.ac.uk/id/eprint/10164231/1/A%20correlative%20biomarker%20study%20and%20integrative%20prognostic%20model.pdfTest; https://discovery.ucl.ac.uk/id/eprint/10164231Test/

الإتاحة: https://discovery.ucl.ac.uk/id/eprint/10164231/1/A%20correlative%20biomarker%20study%20and%20integrative%20prognostic%20model.pdfTest
https://discovery.ucl.ac.uk/id/eprint/10164231Test/

المؤلفون: Fernández-Pérez, M. P., Pérez-Navarro, Enrique, Alonso Gordoa, Teresa, Conteduca, Vicenza, Font Pous, Albert, Vázquez-Estévez, Sergio, González del Alba, Aránzazu, Wetterskog, Daniel, Antonarakis, Emmanuel S., Mellado González, Begoña, Fernández-Calvo, Ovidio, Méndez-Vidal, María J., Climent, Miguel A., Durán, Ignacio, Gallardo, Enrique, Rodríguez Sánchez, Ángel, Santander, Carmen, Sáez, María Isabel, Puente Vázquez, Javier, Tudela, Julián, Martínez, Alberto, López-Andreo, María J., Padilla, José, Lozano, Rebeca, Hervas, David, Luo, Jun, de Giorgi, Ugo, García-Castellanos, Daniel, Attard, Gerhardt, Grande, Enrique, González-Billalabeitia, E.

المساهمون: Astellas Pharma, Instituto de Salud Carlos III, Ministerio de Sanidad, Servicios Sociales e Igualdad (España), Fundación CRIS contra el Cáncer

مصطلحات موضوعية: Prostate cancer, AR gain, AR-V7, CTCs, TMPRSS2-ERG, Enzalutamide

الوصف: [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. ; The authors would like to acknowledge all the staff at SOGUG for their support to run the PREMIERE trial, Astellas for supporting this research, ISCIII from the Spanish Ministry of Health, and Cris Cancer Foundation for their support. This trial was ...

وصف الملف: application/pdf

العلاقة: Publisher's version; The underlying dataset has been published as supplementary material of the article in the publisher platform at DOI 10.1002/pros.24469; https://doi.org/10.1002/pros.24469Test; Sí; The Prostate 83(4): 376-384 (2023); http://hdl.handle.net/10261/333013Test; http://dx.doi.org/10.13039/501100004948Test; http://dx.doi.org/10.13039/501100003751Test; http://dx.doi.org/10.13039/501100004587Test; 2-s2.0-85145039209; https://api.elsevier.com/content/abstract/scopus_id/85145039209Test

الإتاحة: https://doi.org/10.1002/pros.2446910.13039/50110000494810.13039/50110000375110.13039/501100004587Test
http://hdl.handle.net/10261/333013Test
https://api.elsevier.com/content/abstract/scopus_id/85145039209Test

المؤلفون: Fernandez-Perez, María P., Perez-Navarro, Enrique, Alonso-Gordoa, Teresa, Conteduca, Vincenza, Font, Albert, Vázquez-Estévez, Sergio, González-del-Alba, Aránzazu, Wetterskog, Daniel, Antonarakis, Emmanuel S., Mellado, Begona, Fernandez-Calvo, Ovidio, Méndez-Vidal, María J., Climent, Miguel Ángel, Duran, Ignacio, Gallardo, Enrique, Rodriguez Sanchez, Angel, Santander, Carmen, Sáez, Maria I., Puente, Javier, Tudela, Julian, Martínez, Alberto, López-Andreo, Maria J., Padilla, José, Lozano, Rebeca, Hervas, David, Luo, Jun, De Giorgi, Ugo, Castellano, Daniel, Attard, Gerhardt, Grande, Enrique, Gonzalez-Billalabeitia, Enrique, Universitat Autònoma de Barcelona

مصطلحات موضوعية: AR gain, AR-V7, CTCs, Enzalutamide, Prostate cancer, TMPRSS2-ERG

الوصف: There is a considerable need to incorporate biomarkers of resistance to new antiandrogen agents in the management of castration-resistant prostate cancer (CRPC). 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. 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. 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.

وصف الملف: application/pdf

العلاقة: Ministerio de Economía y Competitividad BA16/00038; Instituto de Salud Carlos III PI18/00883; The Prostate; Vol. 83 (december 2022); https://ddd.uab.cat/record/281329Test; urn:10.1002/pros.24469; urn:oai:ddd.uab.cat:281329; urn:pmcid:PMC10107622; urn:pmc-uid:10107622; urn:pmid:36564933; urn:oai:pubmedcentral.nih.gov:10107622

الإتاحة: https://ddd.uab.cat/record/281329Test

المؤلفون: Fernandez‐Perez, María P., Perez‐Navarro, Enrique, Alonso‐Gordoa, Teresa, Conteduca, Vicenza, Font, Albert, Vázquez‐Estévez, Sergio, González‐del‐Alba, Aránzazu, Wetterskog, Daniel, Antonarakis, Emmanuel S., Mellado, Begona, Fernandez‐Calvo, Ovidio, Méndez‐Vidal, María J., Climent, Miguel A., Duran, Ignacio, Gallardo, Enrique, Rodriguez Sanchez, Angel, Santander, Carmen, Sáez, Maria I., Puente, Javier, Tudela, Julian, Martínez, Alberto, López‐Andreo, Maria J., Padilla, José, Lozano, Rebeca, Hervas, David, Luo, Jun, de Giorgi, Ugo, Castellano, Daniel, Attard, Gerhardt, Grande, Enrique, Gonzalez‐Billalabeitia, Enrique

المساهمون: Astellas, Instituto de Salud Carlos III

المصدر: The Prostate ; volume 83, issue 4, page 376-384 ; ISSN 0270-4137 1097-0045

الوصف: 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.

الإتاحة: https://doi.org/10.1002/pros.24469Test