Bup and Bev were tolerable and showed preliminary activity in VEGF-refractory metastatic renal cell carcinoma (n = 32). The MTD for Bup was 80 mg/d. The PR was 11% (95% CI: 1–33%) for those treated at MTD. The OS, PFS and median TTF were 18% (95% CI: 4–N.E.); 9% (95% CI: 2–9%) and 4% (95% CI: 2–9%). 2 patients had an activating PIK3CA mutation, 1 of which achieved a PR (TTF-13 months) and the other exhibited a 16% tumor shrinkage (TTF-9 months). The gene discussed is VEGFA; the disease is neoplasm.