Benefit of Atrasentan in Men with Hormone Refractory Prostate Cancer Metastatic to Bone

Abstract

4687 Background: Bone alkaline phosphatase (BAP) predicts time to progression (TTP) and survival in patients with hormone refractory prostate cancer (HRPC). We tested 2 hypotheses: a) BAP at baseline is predictive of both TTP and survival in HRPC patients with bony metastases only and b) BAP predicts response to atrasentan therapy in these men. Methods: Data were analyzed from 474 men with HRPC metastastic only to bone from a randomized, double-blind, placebo-controlled phase 3 trial of atrasentan 10 mg QD. Kaplan-Meier and Cox proportional hazard methodologies were used to compare TTP (a composite of radiological and clinical outcomes) between treatments. Values from 451 patients with baseline BAP values were analyzed. Data from treatment arms were pooled and stratified by baseline BAP < and >/= the median value. TTP and survival and the effect of treatment within the 2 groups were compared using Kaplan-Meier methodology. Results: 253 patients received atrasentan, 221 received placebo; atrasentan resulted in a significant delay in TTP versus placebo (p=0.026). The median baseline BAP value was 31.5 ng/mL. Median TTP for patients whose baseline BAP < median was 168 days versus 85 days for patients with baseline BAP >/= median (p<0.001) and median time to death was 741 days vs 461 days for patients with BAP < median and >/= median, respectively (p<0.001). In patients with a baseline BAP >/= median, atrasentan significantly delayed TTP versus placebo, while in patients with baseline BAP < median, treatment effect did not reach significance (table). Conclusions: These data confirm that high baseline BAP is predictive of early disease progression and reduced survival in HRPC patients with only bone metastases, independent of therapy. Atrasentan therapy significantly delayed TTP versus placebo in subjects with bone metastases only. It also significantly increased TTP in bony metastatic HRPC patients with a high baseline BAP. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Abbott Laboratories Abbott Laboratories