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Novel potential predictive markers of sunitinib outcomes in long-term responders versus primary refractory patients with metastatic clear-cell renal cell carcinoma
- Source :
- Oncotarget, r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau, instname, RUC. Repositorio da Universidade da Coruña, Dipòsit Digital de la UB, Universidad de Barcelona, Zaguán. Repositorio Digital de la Universidad de Zaragoza, Repositorio Institucional de la Consejería de Sanidad de la Comunidad de Madrid, Consejería de Sanidad de la Comunidad de Madrid, Dipòsit Digital de Documents de la UAB, Universitat Autònoma de Barcelona
- Publication Year :
- 2017
- Publisher :
- Impact Journals, 2017.
-
Abstract
- [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. PPfizer; SOGUG-2011-05 Ministerio de Economía, Industria y Competitividad; SAF2015-66015-R Ministerio de Economía, Industria y Competitividad; ISCIII-RETIC RD12/0036/0009 Ministerio de Economía, Industria y Competitividad; PIE 15/00076
- Subjects :
- Male
0301 basic medicine
Oncology
Indoles
sunitinib
Kaplan-Meier Estimate
urologic and male genital diseases
primary refractory
Càncer de ronyó
Metastasis
0302 clinical medicine
Renal cell carcinoma
Molecular Targeted Therapy
Hematology
Sunitinib
Biochemical markers
Prognosis
Renal cancer
030220 oncology & carcinogenesis
Cohort
Marcadors bioquímics
Female
Signal Transduction
Research Paper
medicine.drug
medicine.medical_specialty
Antineoplastic Agents
macromolecular substances
metastatic renal cell carcinoma
03 medical and health sciences
Internal medicine
Biomarkers, Tumor
medicine
Mortalitat
Humans
Pyrroles
Mortality
Carcinoma, Renal Cell
Neoplasm Staging
Retrospective Studies
business.industry
Gene Expression Profiling
biomarkers
Retrospective cohort study
Biomarker
medicine.disease
MicroRNAs
Clear cell renal cell carcinoma
030104 developmental biology
ROC Curve
Drug Resistance, Neoplasm
long-term responders
business
Progressive disease
Subjects
Details
- Language :
- English
- ISSN :
- 19492553
- Database :
- OpenAIRE
- Journal :
- Oncotarget, r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau, instname, RUC. Repositorio da Universidade da Coruña, Dipòsit Digital de la UB, Universidad de Barcelona, Zaguán. Repositorio Digital de la Universidad de Zaragoza, Repositorio Institucional de la Consejería de Sanidad de la Comunidad de Madrid, Consejería de Sanidad de la Comunidad de Madrid, Dipòsit Digital de Documents de la UAB, Universitat Autònoma de Barcelona
- Accession number :
- edsair.doi.dedup.....fdfa82e8640a2be321c0a3e9ca9d5fce