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

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. Multicenter, observational, retrospective study in patients with clear-cell mRCC treated wit...

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Autores: Puente, J.|||0000-0002-6910-1331, Laínez, Nuria, Dueñas, Marta, Mendez Vidal, María José|||0000-0002-7460-1859, Esteban, Emilio, Castellano, Daniel|||0000-0002-9106-0687, Martinez-Fernández, Mónica, Basterretxea, Laura, Juan-Fita, María José, Antón Aparicio, Luís, Leon-Mateos, Luis, Lambea, Julio, Pérez Valderrama, Begoña|||0000-0003-0175-1263, Vázquez, Sergio|||0000-0002-2203-0791, Suárez, Cristina|||0000-0002-0502-5528, Garcia del Muro, Xavier|||0000-0001-5571-2847, Gallardo Díaz, Enrique|||0000-0002-1375-3488, Maroto Rey, Pablo|||0000-0002-0030-0412, Samaniego, M. Luz, Suárez-Paniagua, Beatriz, Sanz, Julián, Paramio, Jesús M.|||0000-0001-7520-3177
Tipo de recurso: artículo
Fecha de publicación:2017
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:186213
Acceso en línea:https://ddd.uab.cat/record/186213
https://dx.doi.org/urn:doi:10.18632/oncotarget.16494
Access Level:acceso abierto
Palabra clave:Sunitinib
Metastatic renal cell carcinoma
Biomarkers
Long-term responders
Primary refractory
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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, J.|||0000-0002-6910-1331Laínez, NuriaDueñas, MartaMendez Vidal, María José|||0000-0002-7460-1859Esteban, EmilioCastellano, Daniel|||0000-0002-9106-0687Martinez-Fernández, MónicaBasterretxea, LauraJuan-Fita, María JoséAntón Aparicio, LuísLeon-Mateos, LuisLambea, JulioPérez Valderrama, Begoña|||0000-0003-0175-1263Vázquez, Sergio|||0000-0002-2203-0791Suárez, Cristina|||0000-0002-0502-5528Garcia del Muro, Xavier|||0000-0001-5571-2847Gallardo Díaz, Enrique|||0000-0002-1375-3488Maroto Rey, Pablo|||0000-0002-0030-0412Samaniego, M. LuzSuárez-Paniagua, BeatrizSanz, JuliánParamio, Jesús M.|||0000-0001-7520-3177SunitinibMetastatic renal cell carcinomaBiomarkersLong-term respondersPrimary refractorySeveral potential predictive markers of efficacy of targeted agents in patients with metastatic renal cell carcinoma (mRCC) have been identified. Interindividual heterogeneity warrants further investigation. 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. 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. 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.Universitat Autònoma de Barcelona 22017-01-0120172017-01-01Articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://ddd.uab.cat/record/186213https://dx.doi.org/urn:doi:10.18632/oncotarget.16494reponame:Dipòsit Digital de Documents de la UABinstname:Universitat Autònoma de BarcelonaInglésengInstituto de Salud Carlos III https://doi.org/10.13039/501100004587 RETIC/RD12-0036-0009Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 PI15/00076Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 CB16/12/00228open accesshttp://purl.org/coar/access_right/c_abf2Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.https://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:ddd.uab.cat:1862132026-06-06T12:50:31Z
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, J.|||0000-0002-6910-1331
Sunitinib
Metastatic renal cell carcinoma
Biomarkers
Long-term responders
Primary refractory
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, J.|||0000-0002-6910-1331
Laínez, Nuria
Dueñas, Marta
Mendez Vidal, María José|||0000-0002-7460-1859
Esteban, Emilio
Castellano, Daniel|||0000-0002-9106-0687
Martinez-Fernández, Mónica
Basterretxea, Laura
Juan-Fita, María José
Antón Aparicio, Luís
Leon-Mateos, Luis
Lambea, Julio
Pérez Valderrama, Begoña|||0000-0003-0175-1263
Vázquez, Sergio|||0000-0002-2203-0791
Suárez, Cristina|||0000-0002-0502-5528
Garcia del Muro, Xavier|||0000-0001-5571-2847
Gallardo Díaz, Enrique|||0000-0002-1375-3488
Maroto Rey, Pablo|||0000-0002-0030-0412
Samaniego, M. Luz
Suárez-Paniagua, Beatriz
Sanz, Julián
Paramio, Jesús M.|||0000-0001-7520-3177
author Puente, J.|||0000-0002-6910-1331
author_facet Puente, J.|||0000-0002-6910-1331
Laínez, Nuria
Dueñas, Marta
Mendez Vidal, María José|||0000-0002-7460-1859
Esteban, Emilio
Castellano, Daniel|||0000-0002-9106-0687
Martinez-Fernández, Mónica
Basterretxea, Laura
Juan-Fita, María José
Antón Aparicio, Luís
Leon-Mateos, Luis
Lambea, Julio
Pérez Valderrama, Begoña|||0000-0003-0175-1263
Vázquez, Sergio|||0000-0002-2203-0791
Suárez, Cristina|||0000-0002-0502-5528
Garcia del Muro, Xavier|||0000-0001-5571-2847
Gallardo Díaz, Enrique|||0000-0002-1375-3488
Maroto Rey, Pablo|||0000-0002-0030-0412
Samaniego, M. Luz
Suárez-Paniagua, Beatriz
Sanz, Julián
Paramio, Jesús M.|||0000-0001-7520-3177
author_role author
author2 Laínez, Nuria
Dueñas, Marta
Mendez Vidal, María José|||0000-0002-7460-1859
Esteban, Emilio
Castellano, Daniel|||0000-0002-9106-0687
Martinez-Fernández, Mónica
Basterretxea, Laura
Juan-Fita, María José
Antón Aparicio, Luís
Leon-Mateos, Luis
Lambea, Julio
Pérez Valderrama, Begoña|||0000-0003-0175-1263
Vázquez, Sergio|||0000-0002-2203-0791
Suárez, Cristina|||0000-0002-0502-5528
Garcia del Muro, Xavier|||0000-0001-5571-2847
Gallardo Díaz, Enrique|||0000-0002-1375-3488
Maroto Rey, Pablo|||0000-0002-0030-0412
Samaniego, M. Luz
Suárez-Paniagua, Beatriz
Sanz, Julián
Paramio, Jesús M.|||0000-0001-7520-3177
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universitat Autònoma de Barcelona
dc.subject.none.fl_str_mv Sunitinib
Metastatic renal cell carcinoma
Biomarkers
Long-term responders
Primary refractory
topic Sunitinib
Metastatic renal cell carcinoma
Biomarkers
Long-term responders
Primary refractory
description 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. 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. 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. 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 2
2017-01-01
2017
2017-01-01
dc.type.none.fl_str_mv Article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://ddd.uab.cat/record/186213
https://dx.doi.org/urn:doi:10.18632/oncotarget.16494
url https://ddd.uab.cat/record/186213
https://dx.doi.org/urn:doi:10.18632/oncotarget.16494
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.relation.none.fl_str_mv Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 RETIC/RD12-0036-0009
Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 PI15/00076
Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 CB16/12/00228
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Dipòsit Digital de Documents de la UAB
instname:Universitat Autònoma de Barcelona
instname_str Universitat Autònoma de Barcelona
reponame_str Dipòsit Digital de Documents de la UAB
collection Dipòsit Digital de Documents de la UAB
repository.name.fl_str_mv
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