Preliminary antitumor activity of BAY 43–9006 in metastatic renal cell carcinoma and other advanced refractory solid tumors in a phase II randomized discontinuation trial (RDT)

4501 Background: BAY 43–9006 (BAY) is a novel signal transduction inhibitor that prevents tumor cell proliferation and angiogenesis through blockade of the Raf/MEK/ERK pathway at the level of Raf kinase and the receptor tyrosine kinases VEGFR-2 and PDGFR-β. The phase II RDT study was undertaken to determine the antitumor activity (either regression or disease stabilization) of BAY in patients (pts) with a variety of advanced refractory solid tumors. Methods: Pts were enrolled in a placebo-controlled, RDT consisting of a 12-week induction phase, in which pts received 400 mg bid oral BAY, followed by a randomization phase. At the end of the 12-week phase pts whose target lesion tumor burden showed growth >25% (progressive disease PD) were discontinued. Pts whose target lesion tumor burden showed shrinkage ≥25% (responders) continued open label BAY until PD or toxicity. Pts whose target tumor lesion remained within 25% of baseline (stable disease SD) were randomized to receive 400 mg bid oral BAY or placebo. Results: In 14 months, 397 pts were enrolled. The most common tumor types were colorectal (CRC), renal cell carcinoma (RCC) and melanoma. Typical drug-related toxicities were hand-foot skin reaction, rash, fatigue, diarrhea, anorexia and hypertension. Tumor regressions were observed in multiple tumor types including RCC, CRC, melanoma, thyroid, sarcoma and pancreas. Of the 112 pts with RCC, 65 pts have reached the initial 12-week assessment (63 evaluable for response). Response evaluation by investigator demonstrated 25 responders, 18 SD and 15 PD. Five pts discontinued due to other reasons (e.g. adverse event or withdrawal of consent). Conclusions: BAY has activity (as measured by disease regressions) in multiple tumor types, particularly RCC, and is well tolerated in pts with advanced cancers. The randomized portion will provide information about BAY's disease-stabilizing effect and long-term safety, in particular in pts with RCC. An ongoing phase III study in RCC will assess BAY's effect on time to progression and survival. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bayer Pharmaceutical Corp. Bayer Bayer Pharmaceuticals Bayer