Angiogenesis is a critical process in the progression of advanced renal cell carcinoma. Agents targeting angiogenesis have played a primary role in the treatment of metastatic renal cell carcinoma. However, resistance to anti-angiogenesis therapy almost always occurs, and major progress has been made in understanding its underlying molecular mechanism. Axitinib and everolimus have been used extensively in patients whom have had disease progression after prior anti-angiogenesis therapy. Recently, several new agents have been shown to improve overall survival in comparison with everolimus. This review provides an in-depth summary of drugs employable in the clinical setting, the rationale to their use, and the studies conducted leading to their approval for use and provides perspective on the paradigm shift in the treatment of renal cell carcinoma. Highlighted are the newly approved agents cabozantinib, nivolumab, and lenvatinib for advanced renal cell carcinoma patients treated with prior anti-angiogenesis therapy.

The rate of venous thromboembolism (VTE) has been reported to be higher in blacks compared to whites. Non-O blood types have also been associated with a significantly higher VTE risk. Given that a higher proportion of blacks have O blood type, one might have expected that black individuals would have fewer VTE. In this study, we analyzed race, gender, age, ABO/Rh blood type and VTE risk in 60,982 black and white patients admitted over a span of 10 years. The overall occurrence of VTE was 7.6%, higher in males (8.7% males vs. 7.2% females), higher in non-O blood types (8.5% non-O vs. 6.9% O blood type), and increasing with age (5.8% <65yrs, 11.3% ≥65yrs). No difference in VTE rate was noted with Rh antigen positivity. When stratified by age, VTE rate was consistently higher in blacks and non-O blood types. No difference was detected among the various non-O blood types. To assess the potential confounder of comorbidities, we stratified patients according to Charlson comorbidity score. In a subgroup of healthy patients with age-independent Charlson comorbidity scores of 0 (N=28,387), blacks still had an increased VTE risk and this risk was still higher with increasing age and in those with non-O blood types. We conclude that black race and non-O blood types have increased VTE risk when stratified for age and that associated comorbidities do not explain these differences.