Web of Science: 4 citations, Scopus: 4 citations, Google Scholar: citations,
Novel potential predictive markers of sunitinib outcomes in long-term responders versus primary refractory patients with metastatic clear-cell renal cell carcinoma
Puente, Javier (Hospital Clínico Universitario San Carlos)
Laínez, Nuria (Medical Oncology Department, Complejo Hospitalario de Navarra, Pamplona, Spain)
Dueñas, Marta (CIBERONC, Spain)
Méndez-Vidal, María José (Medical Oncology Department, Hospital Universitario Reina Sofía, Córdoba, Spain)
Esteban, Emilio (Medical Oncology Department, Hospital Universitario Central de Asturias, Oviedo, Spain)
Castellano, Daniel (Medical Oncology Department, and Instituto Investigación Biomédica, Hospital Universitario 12 de Octubre, Madrid, Spain)
Martinez-Fernández, Mónica (CIBERONC, Spain)
Basterretxea, Laura (Medical Oncology Department, Hospital Donostia, Donostia, Spain)
Juan-Fita, María José (Medical Oncology Department, Instituto Valenciano de Oncología, Valencia, Spain)
Antón, Luis (Medical Oncology Department, Complejo Hospitalario Universitario de A Coruña, A Coruña, Spain)
León, Luis (Promoción e Planificación da Investigación Sanitaria, Axencia de Coñecemento en Saúde, Santiago de Compostela, Spain)
Lambea, Julio (Medical Oncology Department, Hospital Clínico de Zaragoza, Zaragoza, Spain)
Pérez-Valderrama, Begoña (Medical Oncology Department, Hospital Universitario Virgen del Rocío, Sevilla, Spain)
Vázquez, Sergio (Medical Oncology Department, Hospital Universitario Lucus Augusti, Lugo, Spain)
Suarez, Cristina (Universitat Autònoma de Barcelona)
del Muro, Xavier Garcia (Institut Català d'Oncologia, Hospital Duran i Reynals)
Gallardo, Enrique (Medical Oncology Department, Hospital Universitari Parc Taulí, Sabadell, Spain)
Maroto, José Pablo (Institut d'Investigacions Biomèdiques Sant Pau)
Samaniego, M Luz (Statistical Department, Trial Form Support TFS people, Madrid, Spain)
Suárez-Paniagua, Beatriz (Oncology Medical Department, Trial Form Support, Madrid, Spain)
Sanz, Julián (Pathology Department, Hospital Clínico Universitario San Carlos, Madrid, Spain)
Paramio, Jesús M. (CIBERONC, Spain)

Date: 2017
Abstract: 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.
Note: Altres ajuts : SOGUG-2011-05
Note: Número d'acord de subvenció SAF/2015/66015-R
Note: Número d'acord de subvenció ISCIII-RETIC/RD12-0036-0009
Note: Número d'acord de subvenció ISCIII/PIE 15-00076
Note: Número d'acord de subvenció ISCII/CB16 12-00228
Rights: Aquest 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. Creative Commons
Language: Anglès.
Document: article ; recerca ; publishedVersion
Subject: Sunitinib ; Metastatic renal cell carcinoma ; Biomarkers ; Long-term responders ; Primary refractory
Published in: Oncotarget, Vol. 8 (march 2017) , p. 30410-30421, ISSN 1949-2553

PMID: 28423742
DOI: 10.18632/oncotarget.16494

12 p, 5.3 MB

The record appears in these collections:
Research literature > UAB research groups literature > Research Centres and Groups (scientific output) > Health sciences and biosciences > Institut d'Investigació Biomèdica Sant Pau
Articles > Research articles
Articles > Published articles

 Record created 2018-02-08, last modified 2019-02-06

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