Final findings from a phase II, placebo-controlled, randomized discontinuation trial (RDT) of sorafenib (BAY 43–9006) in patients with advanced renal cell carcinoma (RCC)
4544 Background: BAY 43–9006 (BAY) is a Raf kinase and VEGFR inhibitor with effects on both tumor proliferation and angiogenesis. This Phase II RDT determined the effects of BAY on tumor growth in patients (pts) with stable disease (SD) after 12 wks treatment. Methods: 202 pts with advanced RCC (ECOG 1–2) entered a 12-wk induction phase (BAY 400 mg po bid). Pts with bidimensional tumor measurements remaining within 25% of baseline (SD) were then randomized (double-blind) to BAY 400 mg bid or placebo (Pb), and the progression-free rate [percentage of pts with SD or response] at 24 wks compared. Results: 65 pts with SD at 12 wks were randomized to BAY (n=32) or Pb (n=33); pt characteristics were well matched between groups. After 24 wks, 6 pts (18%) on Pb were progression-free compared with 16 pts (50%) on BAY (p=0.0077). Median progression-free survival (PFS) after randomization was greater with BAY vs Pb (23 vs 6 wks, p=0.0001, hazard ratio 0.29). BAY was restarted in 25 pts who progressed on Pb after a median time from randomization of 7 wks. Median PFS after restarting BAY in these pts was 24 wks; 13 pts are ongoing. The most common drug-related AEs in all 202 pts with RCC were rash (62%), hand-foot skin reaction (HFS; 61%) and fatigue (56%). Grade 3/4 drug-related AEs occurred in 47% of patients; the most common were hypertension (24%), HFS (13%) and fatigue (5%). Drug-related AEs led to discontinuation in 2% of pts, and no deaths. Conclusions: These Phase II data prove that BAY had a marked effect on PFS in pts with metastatic RCC, with an acceptable toxicity profile. The RDT (with design modifications to improve efficiency) should be considered for Phase II trials of other drugs with putative effects on disease stabilization.