Novel potential predictive markers of sunitinib outcomes in long-term responders versus primary refractory patients with metastatic clear-cell renal cell carcinoma

Background: several potential predictive markers of efficacy of targeted agents in patients with metastatic renal cell carcinoma (mRCC) have been identified. Interindividual heterogeneity warrants further investigation. Patients and methods: multicenter, observational, retrospective study in patient...

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Autores: Puente, Javier, Lainez, Nuria, Dueñas, Marta, Méndez-Vidal, María José, Esteban, Emilio, Castellano, Daniel, Martinez-Fernández, Mónica, Basterretxea, Laura, Juan Fita, María José, Antón, Luis, León, Luis, Lambea, Julio, Pérez-Valderrama, Begoña, Vázquez, Sergio, Suarez, Cristina, García del Muro Solans, Xavier, Gallardo, Enrique, Maroto, José Pablo, Samaniego, M. Luz, Suárez-Paniagua, Beatriz, Sanz, Julián, Paramio, Jesús M., SOGUG (Spanish Oncology Genitourinary Group)
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2017
País:España
Recursos:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/178656
Acesso em linha:https://hdl.handle.net/2445/178656
Access Level:acceso abierto
Palavra-chave:Marcadors bioquímics
Càncer de ronyó
Mortalitat
Biochemical markers
Renal cancer
Mortality
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spelling Novel potential predictive markers of sunitinib outcomes in long-term responders versus primary refractory patients with metastatic clear-cell renal cell carcinomaPuente, JavierLainez, NuriaDueñas, MartaMéndez-Vidal, María JoséEsteban, EmilioCastellano, DanielMartinez-Fernández, MónicaBasterretxea, LauraJuan Fita, María JoséAntón, LuisLeón, LuisLambea, JulioPérez-Valderrama, BegoñaVázquez, SergioSuarez, CristinaGarcía del Muro Solans, XavierGallardo, EnriqueMaroto, José PabloSamaniego, M. LuzSuárez-Paniagua, BeatrizSanz, JuliánParamio, Jesús M.SOGUG (Spanish Oncology Genitourinary Group)Marcadors bioquímicsCàncer de ronyóMortalitatBiochemical markersRenal cancerMortalityBackground: several potential predictive markers of efficacy of targeted agents in patients with metastatic renal cell carcinoma (mRCC) have been identified. Interindividual heterogeneity warrants further investigation. Patients and methods: multicenter, observational, retrospective study in patients with clear-cell mRCC treated with sunitinib. Patients were classified in two groups: long-term responders (LR) (progression-free survival (PFS)≥22 months and at least stable disease), and primary refractory (PR) (progressive disease within 3-months of sunitinib onset). Objectives were to compare baseline clinical factors in both populations and to correlate tumor expression of selected signaling pathways components with sunitinib PFS. Results: 123 patients were analyzed (97 LR, 26 PR). In the LR cohort, overall response rate was 79% and median duration of best response was 30 months. Median PFS and overall survival were 43.2 (95% confidence intervals[CI]:37.2-49.3) and 63.5 months (95%CI:55.1-71.9), respectively. At baseline PR patients had a significantly lower proportion of nephrectomies, higher lactate dehydrogenase and platelets levels, lower hemoglobin, shorter time to and higher presence of metastases, and increased Fuhrman grade. Higher levels of HEYL, HEY and HES1 were observed in LR, although only HEYL discriminated populations significantly (AUC[ROC]=0.704; cut-off=34.85). Increased levels of hsa-miR-27b, hsa-miR-23b and hsa-miR-628-5p were also associated with prolonged survival. No statistical significant associations between hsa-miR-23b or hsa-miR-27b and the expression of c-Met were found. Conclusions: certain mRCC patients treated with sunitinib achieve extremely long-term responses. Favorable baseline hematology values and longer time to metastasis may predict longer PFS. HEYL, hsa-miR-27b, hsa-miR-23b and hsa-miR-628-5p could be potentially used as biomarkers of sunitinib response.Impact Journals2017info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/178656Articles publicats en revistes (Ciències Clíniques)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció del document publicat a: https://doi.org/10.18632/oncotarget.16494Oncotarget, 2017, vol. 8, num. 18, p. 30410-30421https://doi.org/10.18632/oncotarget.16494cc-by (c) Puente, Javier et al., 2017https://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/1786562026-05-27T06:46:51Z
dc.title.none.fl_str_mv Novel potential predictive markers of sunitinib outcomes in long-term responders versus primary refractory patients with metastatic clear-cell renal cell carcinoma
title Novel potential predictive markers of sunitinib outcomes in long-term responders versus primary refractory patients with metastatic clear-cell renal cell carcinoma
spellingShingle Novel potential predictive markers of sunitinib outcomes in long-term responders versus primary refractory patients with metastatic clear-cell renal cell carcinoma
Puente, Javier
Marcadors bioquímics
Càncer de ronyó
Mortalitat
Biochemical markers
Renal cancer
Mortality
title_short Novel potential predictive markers of sunitinib outcomes in long-term responders versus primary refractory patients with metastatic clear-cell renal cell carcinoma
title_full Novel potential predictive markers of sunitinib outcomes in long-term responders versus primary refractory patients with metastatic clear-cell renal cell carcinoma
title_fullStr Novel potential predictive markers of sunitinib outcomes in long-term responders versus primary refractory patients with metastatic clear-cell renal cell carcinoma
title_full_unstemmed Novel potential predictive markers of sunitinib outcomes in long-term responders versus primary refractory patients with metastatic clear-cell renal cell carcinoma
title_sort Novel potential predictive markers of sunitinib outcomes in long-term responders versus primary refractory patients with metastatic clear-cell renal cell carcinoma
dc.creator.none.fl_str_mv Puente, Javier
Lainez, Nuria
Dueñas, Marta
Méndez-Vidal, María José
Esteban, Emilio
Castellano, Daniel
Martinez-Fernández, Mónica
Basterretxea, Laura
Juan Fita, María José
Antón, Luis
León, Luis
Lambea, Julio
Pérez-Valderrama, Begoña
Vázquez, Sergio
Suarez, Cristina
García del Muro Solans, Xavier
Gallardo, Enrique
Maroto, José Pablo
Samaniego, M. Luz
Suárez-Paniagua, Beatriz
Sanz, Julián
Paramio, Jesús M.
SOGUG (Spanish Oncology Genitourinary Group)
author Puente, Javier
author_facet Puente, Javier
Lainez, Nuria
Dueñas, Marta
Méndez-Vidal, María José
Esteban, Emilio
Castellano, Daniel
Martinez-Fernández, Mónica
Basterretxea, Laura
Juan Fita, María José
Antón, Luis
León, Luis
Lambea, Julio
Pérez-Valderrama, Begoña
Vázquez, Sergio
Suarez, Cristina
García del Muro Solans, Xavier
Gallardo, Enrique
Maroto, José Pablo
Samaniego, M. Luz
Suárez-Paniagua, Beatriz
Sanz, Julián
Paramio, Jesús M.
SOGUG (Spanish Oncology Genitourinary Group)
author_role author
author2 Lainez, Nuria
Dueñas, Marta
Méndez-Vidal, María José
Esteban, Emilio
Castellano, Daniel
Martinez-Fernández, Mónica
Basterretxea, Laura
Juan Fita, María José
Antón, Luis
León, Luis
Lambea, Julio
Pérez-Valderrama, Begoña
Vázquez, Sergio
Suarez, Cristina
García del Muro Solans, Xavier
Gallardo, Enrique
Maroto, José Pablo
Samaniego, M. Luz
Suárez-Paniagua, Beatriz
Sanz, Julián
Paramio, Jesús M.
SOGUG (Spanish Oncology Genitourinary Group)
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Marcadors bioquímics
Càncer de ronyó
Mortalitat
Biochemical markers
Renal cancer
Mortality
topic Marcadors bioquímics
Càncer de ronyó
Mortalitat
Biochemical markers
Renal cancer
Mortality
description Background: several potential predictive markers of efficacy of targeted agents in patients with metastatic renal cell carcinoma (mRCC) have been identified. Interindividual heterogeneity warrants further investigation. Patients and methods: multicenter, observational, retrospective study in patients with clear-cell mRCC treated with sunitinib. Patients were classified in two groups: long-term responders (LR) (progression-free survival (PFS)≥22 months and at least stable disease), and primary refractory (PR) (progressive disease within 3-months of sunitinib onset). Objectives were to compare baseline clinical factors in both populations and to correlate tumor expression of selected signaling pathways components with sunitinib PFS. Results: 123 patients were analyzed (97 LR, 26 PR). In the LR cohort, overall response rate was 79% and median duration of best response was 30 months. Median PFS and overall survival were 43.2 (95% confidence intervals[CI]:37.2-49.3) and 63.5 months (95%CI:55.1-71.9), respectively. At baseline PR patients had a significantly lower proportion of nephrectomies, higher lactate dehydrogenase and platelets levels, lower hemoglobin, shorter time to and higher presence of metastases, and increased Fuhrman grade. Higher levels of HEYL, HEY and HES1 were observed in LR, although only HEYL discriminated populations significantly (AUC[ROC]=0.704; cut-off=34.85). Increased levels of hsa-miR-27b, hsa-miR-23b and hsa-miR-628-5p were also associated with prolonged survival. No statistical significant associations between hsa-miR-23b or hsa-miR-27b and the expression of c-Met were found. Conclusions: certain mRCC patients treated with sunitinib achieve extremely long-term responses. Favorable baseline hematology values and longer time to metastasis may predict longer PFS. HEYL, hsa-miR-27b, hsa-miR-23b and hsa-miR-628-5p could be potentially used as biomarkers of sunitinib response.
publishDate 2017
dc.date.none.fl_str_mv 2017
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/178656
url https://hdl.handle.net/2445/178656
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.18632/oncotarget.16494
Oncotarget, 2017, vol. 8, num. 18, p. 30410-30421
https://doi.org/10.18632/oncotarget.16494
dc.rights.none.fl_str_mv cc-by (c) Puente, Javier et al., 2017
https://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by (c) Puente, Javier et al., 2017
https://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Impact Journals
publisher.none.fl_str_mv Impact Journals
dc.source.none.fl_str_mv Articles publicats en revistes (Ciències Clíniques)
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,300719

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