4563 Background: Atrasentan (Xinlay), a selective endothelin-A receptor antagonist, has been studied in 2 randomized placebo controlled studies of men with metastatic hormone-refractory prostate cancer (HRPC) using time to disease progression as the primary endpoint. A meta-analysis of these studies was performed to more precisely define the clinical benefit of atrasentan 10 mg in this patient population. Methods: A meta-analysis using subject-specific data was conducted on the intent-to-treat populations of both studies. Time to disease progression (TTP), time to bone pain (TTBP), as well as time to prostate specific antigen (TTPSA) and bone alkaline phosphatase (TTBALP) progression were analyzed by Kaplan-Meier methodology and by Cox proportional hazards modeling, both stratified by study. Results: 1002 patients were randomized to either atrasentan 10 mg (n=497) or placebo (n=505) in the 2 studies. Atrasentan 10 mg resulted in a statistically significant delay in TTP (log-rank p=0.045), TTBP (log-rank p=0.025), TTPSA (log-rank p=0.002), and TTBALP progression (log-rank p <0.001) compared with placebo. Compared with patients receiving placebo, patients treated with atrasentan 10 mg were 14% less likely to experience disease progression (HR=0.863; 95% CI=0.747, 0.997), had an 18% less likelihood of experiencing bone pain (HR=0.819; 95% CI=0.687, 0.976), had a 22% less chance of experiencing PSA progression (HR=0.775; 95% CI=0.657, 0.914), and were 46% less likely to experience BAP progression (HR=0.537; 95% CI=0.414, 0.695). The relative probability of remaining progression-free was 10% greater at 3 months and 22% greater at 6 months for patients treated with atrasentan 10 mg compared with those treated with placebo, where the probability of remaining progression-free on placebo was 49% and 27% at 3 and 6 months respectively. Conclusions: The results of this analysis demonstrate that atrasentan 10 mg, a novel cytostatic agent, provides significant clinical benefit to patients with metastatic HRPC and indicate that atrasentan would be a valuable addition to the limited treatment options available for these men. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Abbott Laboratories Abbott Laboratories Abbott Laboratories Abbott Laboratories, Aventis, OSI Abbott Laboratories, AstraZeneca, Lilly Oncology, NCI