부산대학교 도서관

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. Keywords: c-Myc, clear-cell renal cell carcinoma, HIF, sunitinib
Introduction Clear-cell renal cell carcinoma (ccRCC) is the most common type of adult kidney cancer. Local recurrence or distant metastasis develops in up to 40% of the patients treated for [...]