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Title: Novel potential predictive markers of sunitinib outcomes in long-term responders versus primary refractory patients with metastatic clear-cell renal cell carcinoma
Author: 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)
Keywords: Marcadors bioquímics
Càncer de ronyó
Biochemical markers
Renal cancer
Issue Date: 2-May-2017
Publisher: Impact Journals
Abstract: 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.
Note: Reproducció del document publicat a:
It is part of: Oncotarget, 2017, vol. 8, num. 18, p. 30410-30421
Related resource:
ISSN: 1949-2553
Appears in Collections:Articles publicats en revistes (Ciències Clíniques)
Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

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