RT Journal Article
T1 Novel potential predictive markers of sunitinib outcomes in long-term responders versus primary refractory patients with metastatic clear-cell renal cell carcinoma.
A1 Puente, Javier
A1 Laínez, Nuria
A1 Dueñas, Marta
A1 Méndez-Vidal, María José
A1 Esteban, Emilio
A1 Castellano, Daniel
A1 Martinez-Fernández, Mónica
A1 Basterretxea, Laura
A1 Juan-Fita, María José
A1 Antón, Luis
A1 León, Luis
A1 Lambea, Julio
A1 Pérez-Valderrama, Begoña
A1 Vázquez, Sergio
A1 Suarez, Cristina
A1 Del Muro, Xavier Garcia
A1 Gallardo, Enrique
A1 Maroto, José Pablo
A1 Samaniego, M Luz
A1 Suárez-Paniagua, Beatriz
A1 Sanz, Julián
A1 Paramio, Jesús M
A1 SOGUG (Spanish Oncology Genitourinary Group), 
K1 biomarkers
K1 long-term responders
K1 metastatic renal cell carcinoma
K1 primary refractory
K1 sunitinib
AB 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.
YR 2017
FD 2017
LK https://hdl.handle.net/10668/25131
UL https://hdl.handle.net/10668/25131
LA en
DS RISalud
RD Apr 12, 2025