HIF pathway and c-Myc as biomarkers for response to sunitinib in metastatic clear-cell renal cell carcinoma
Por:
Maroto, P, Esteban, E, Parra, EF, Mendez-Vidal, MJ, Domenech, M, Perez-Valderrama, B, Calderero, V, Perez-Gracia, JL, Grande, E, Algaba, F
Publicada:
1 ene 2017
Resumen:
Background: Clear-cell renal cell carcinoma (ccRCC) is a heterogeneous disease with a different clinical behavior and response to targeted therapies. Differences in hypoxia-inducible factor (HIF) expression have been used to classify von Hippel-Lindau gene (VHL)-deficient ccRCC tumors. c-Myc may be driving proliferation in HIF-2 alpha-expressing tumors in a growth factor-independent manner.
Objective: To explore the HIF-1 alpha, HIF-2 alpha and c-Myc baseline expression as potential predictors of sunitinib outcome as well as the effectiveness and safety with sunitinib in patients with metastatic ccRCC in routine clinical practice.
Methods: This was an observational and prospective study involving 10 Spanish hospitals. Formalin-fixed, paraffin-embedded primary tumor samples from metastatic ccRCC patients who received sunitinib as first-line treatment were analyzed. Association between biomarker expression and sunitinib treatment outcomes was evaluated. Kaplan-Meier method was applied to measure progression-free survival (PFS) and overall survival.
Results: Eighty-one patients were included: median PFS was 10.8 months (95% CI: 7.4-13.5 months), median overall survival was 21.8 months (95% CI: 14.7-29.8 months) and objective response rate was 40.7%, with 7.4% of patients achieving a complete response. Molecular marker staining was performed in the 69 available tumor samples. Significant association with lower PFS was identified for double c-Myc/HIF-2 alpha-positive staining tumors (median 4.3 vs 11.5 months, hazard ratio = 2.64, 95% CI: 1.03-6.80, P= 0.036). A trend toward a lower PFS was found in positive c-Myc tumors (median 5.9 vs 10.9 months, P= 0.263). HIF-1 alpha and HIF-2 alpha expression levels were not associated with clinical outcome.
Conclusion: These preliminary results suggest that predictive subgroups might be defined based on biomarkers such as c-Myc/HIF-2 alpha. Further validation with more patients will be needed in order to confirm it. Outcomes with sunitinib in metastatic ccRCC in daily clinical practice resemble those obtained in clinical trials.
Filiaciones:
Maroto, P:
Hosp Santa Creu & Sant Pau, Dept Oncol, Barcelona, Spain
Esteban, E:
Nuevo HUCA, Dept Oncol, Oviedo, Spain
Parra, EF:
HU Nuestra Senora Valme, Dept Oncol, Seville, Spain
Mendez-Vidal, MJ:
HU Reina Sofia, Dept Oncol, Cordoba, Spain
Domenech, M:
Hosp Althaia Xarxa Asistencial Manresa, Dept Oncol, Barcelona, Spain
Perez-Valderrama, B:
HU Virgen Rocio, Dept Oncol, Seville, Spain
Calderero, V:
H Fdn Miguel Servet, Dept Oncol, Zaragoza, Spain
Perez-Gracia, JL:
Clin Univ Pamplona, Dept Oncol, Pamplona, Spain
Grande, E:
H Ramon y Cajal, Dept Oncol, Madrid, Spain
Algaba, F:
Univ Autonoma Barcelona, Fdn Puigvert, Pathol Unit, Barcelona, Spain
Green Published, gold, Green Submitted
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