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 San Carlos (Madrid))
Laínez, Nuria (Complejo Hospitalario de Navarra)
Dueñas, Marta (Centro de Investigación Biomédica en Red de Cáncer)
Méndez-Vidal, María José (Hospital Universitario Reina Sofía (Còrdova, Espanya))
Esteban, Emilio (Hospital Universitario Central de Asturias)
Castellano, Daniel (Hospital Universitario 12 de Octubre (Madrid))
Martinez-Fernández, Mónica (Centro de Investigación Biomédica en Red de Cáncer)
Basterretxea, Laura (Hospital Universitario de Donostia (Sant Sebastià, País Basc))
Juan-Fita, María José (Instituto Valenciano Oncologia)
Antón Aparicio, Luís (Complejo Hospitalario Universitario de A Coruña)
Leon-Mateos, Luis (Promoción e Planificación da Investigación Sanitaria, Axencia de Coñecemento en Saúde, Santiago de Compostela, Spain)
Lambea, Julio (Hospital Clínico Universitario "Lozano Blesa" de Zaragoza)
Pérez-Valderrama, Begoña (Hospital Universitario Virgen del Rocío (Sevilla, Andalusia))
Vázquez, Sergio (Hospital Universitario Lucus Augusti (Lugo))
Suárez, Cristina (Universitat Autònoma de Barcelona)
Garcia del Muro, Xavier (Institut Català d'Oncologia)
Gallardo, Enrique (Parc Taulí Hospital Universitari. Institut d'Investigació i Innovació Parc Taulí (I3PT))
Maroto, José Pablo (Institut d'Investigació Biomèdica Sant Pau)
Samaniego, M. Luz (TFS HealthScience)
Suárez-Paniagua, Beatriz (TFS HealthScience)
Sanz, Julián (Hospital Clínico San Carlos (Madrid))
Paramio, Jesús M. (Centro de Investigación Biomédica en Red de Cáncer)
Universitat Autònoma de Barcelona

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.
Grants:	Instituto de Salud Carlos III RETIC/RD12-0036-0009 Ministerio de Economía y Competitividad PI15/00076 Ministerio de Economía y Competitividad CB16/12/00228
Note:	Altres ajuts : SOGUG-2011-05
Note:	Altres ajuts: SAF/2015/66015-R
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.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
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

DOI: 10.18632/oncotarget.16494
PMID: 28423742

12 p, 5.3 MB

The record appears in these collections:
Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Parc Taulí Research and Innovation Institute (I3PT
Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut de Recerca Sant Pau
Articles > Research articles
Articles > Published articles