Extended follow-up from JAVELIN Renal 101: subgroup analysis of avelumab plus axitinib versus sunitinib by the International Metastatic Renal Cell Carcinoma Database Consortium risk group in patients with advanced renal cell carcinoma.

BACKGROUND: We report updated data for avelumab plus axitinib versus sunitinib in patients with advanced renal cell carcinoma from the third interim analysis of the phase III JAVELIN Renal 101 trial. PATIENTS AND METHODS: Progression-free survival (PFS), objective response rate (ORR), and duration of response per investigator assessment (RECIST version 1.1) and overall survival (OS) were evaluated in the overall population and in International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk groups; safety was also assessed. RESULTS: Overall, median OS [95% confidence interval (CI)] was not reached [42.2 months-not estimable (NE)] with avelumab plus axitinib versus 37.8 months (31.4-NE) with sunitinib [hazard ratio (HR) 0.79, 95% CI 0.643-0.969; one-sided P = 0.0116], and median PFS (95% CI) was 13.9 months (11.1-16.6 months) versus 8.5 months (8.2-9.7 months), respectively (HR 0.67, 95% CI 0.568-0.785; one-sided P < 0.0001). In patients with IMDC favorable-, intermediate-, poor-, or intermediate plus poor-risk disease, respectively, HRs (95% CI) for OS with avelumab plus axitinib versus sunitinib were 0.66 (0.356-1.223), 0.84 (0.649-1.084), 0.60 (0.399-0.912), and 0.79 (0.636-0.983), and HRs (95% CIs) for PFS were 0.71 (0.490-1.016), 0.71 (0.578-0.866), 0.45 (0.304-0.678), and 0.66 (0.550-0.787), respectively. ORRs, complete response rates, and durations of response favored avelumab plus axitinib overall and across all risk groups. In the avelumab plus axitinib arm, 81.1% had a grade ≥3 treatment-emergent adverse event (TEAE), and incidences of TEAEs and immune-related AEs were highest <6 months after randomization. CONCLUSIONS: Avelumab plus axitinib continues to show improved efficacy versus sunitinib and a tolerable safety profile overall and across IMDC risk groups. The OS trend favors avelumab plus axitinib versus sunitinib, but data remain immature; follow-up is ongoing. TRIAL REGISTRATION: ClinicalTrials.govNCT02684006; https://clinicaltrials.gov/ct2/show/NCT02684006.

High-density lipoprotein cholesterol affects early endothelial progenitor cell number and endothelial function in obese women.

OBJECTIVE: In order to improve our understanding of high-density lipoprotein cholesterol (HDL-C) cardiovascular (CV) impact in obesity, the association of HDL-C plasma level with circulating early endothelial progenitor cell (early-EPC) number and endothelium-dependent vasodilatation (EDV) in obese women with normal or high low-density lipoprotein cholesterol (LDL-C) plasma levels was evaluated. DESIGN AND METHODS: One hundred thirteen obese female subjects and a control group of 78 healthy female subjects were recruited. Circulating early-EPC were assessed by single- and two-color flow cytometric analyses with a fluorescence activated cell sorting (FACScan) flow cytometer. EDV was evaluated as response to ischemia by strain gauge plethysmography. RESULTS: Both early-EPC number and EDV were significantly decreased in obese women compared with the control group. Obese women with low HDL-C showed a further decrease of early-EPC and EDV in the presence of both high or normal LDL-C plasmatic levels. In the normal HDL-C level subgroup, hypercholesterolemic and nonhypercholesterolemic subjects showed no difference in early-EPC number, whereas slight EDV impairment was present in hypercholesterolemic subjects. CONCLUSION: In obese women, low HDL-C is associated to decreased early-EPC number and impaired EDV, suggesting the need to assess whether evaluation of early-EPC and EDV may increase HDL-C prognostic value in the stratification of CV risk.