Effect of Atrasentan on Slowing Onset of Bone Pain in Hormone-Refractory Prostate Cancer Patients

Darryl J Sleep*, Sandra M Hulting*, Jeffrey D Isaacson*
Abbott, Abbott Park, IL

Introduction: Debilitating bone pain is the major cause of morbidity for prostate cancer patients with bone metastases whose disease has become refractory to standard hormonal therapies (HRPC). Atrasentan is a selective endothelin A receptor antagonist that helps block osteoblast proliferation and exacerbation of metastases to bone. Methods: The effect of atrasentan on bone pain was evaluated for 684 HRPC patients in a large phase 3 randomized double-blind placebo-controlled study whose bone metastases at baseline were confirmed by independent radiologic review (n=352 for 10 mg atrasentan; n=332 for placebo). Kaplan-Meier methods were used to estimate time to an adverse event of bone pain. Treatment effect was compared using log-rank test and Cox proportional hazards ratio (HR). Incidence of bone pain was compared for the treatment arms using Fisher's exact test.
Results: Significantly more placebo recipients experienced bone pain than did atrasentan recipients.

Incidence of Bone Pain n/N (%)			Cox Proportional Model of Time to Bone Pain
Placebo	10 mg Atrasentan	P value	Hazard Ratio	95% CI	Log-rank P value
209/332 (63.0%)	189/352 (53.7%)	.016	.780	.640, .949	.012

Median time to bone pain was 44 days longer for atrasentan-treated subjects than for placebo-treated subjects (121 days versus 77 days). Atrasentan reduced the hazard associated with experiencing bone pain by 22%.
Conclusions: These data demonstrate that atrasentan provides clinical benefit for HRPC patients with bone metastases, specifically a significantly lower incidence and delay in onset of bone pain.

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