Impact of atrasentan on prostate-specific outcomes with hormone refractory prostate cancer patients

Abstract

4582 Background: For men with advanced cancer facing reduced life expectancy and no possibility of cure, symptom relief and maintenance of function are primary objectives of treatment. The Functional Assessment of Cancer Therapy-Prostate (FACT-P) quality of life (QOL) instrument incorporates a disease-specific, 12-item prostate cancer (PCa) subscale (PCS) that includes assessment of PCa-related symptoms such as pain and fatigue. The recently developed FACT Advanced Prostate Symptom Index (FAPSI), an 8-item index derived from the FACT-P, assesses weight loss, urinary problems, pain and fatigue. Scores range from 0–48 for PCS and 0–32 for FAPSI with higher scores indicating better QOL and fewer symptoms. The impact of atrasentan on PCS and FAPSI was evaluated in a phase 3, randomized, placebo-controlled study in men with metastatic hormone refractory PCa (HRPC) (N=809). Methods: All randomized patients with a baseline and final QOL assessment were analyzed. Mean change from baseline to final PCS and FAPSI scores was analyzed using analysis of covariance to compare treatments. The same analyses were performed on a subset of patients (N = 474) with HRPC metastastic only to bone. Results: Patients treated with placebo recorded a greater deterioration in both the PCS and FAPSI than those receiving atrasentan (p=0.032 and p=0.081). For both indices, the treatment difference was greater and statistically significant in men with bone metastases. The difference between groups was less than the minimally important difference (MID) of 3 points. However, as a group, the placebo-treated patients deteriorated beyond the MID, whereas the atrasentan-treated patients did not. Conclusion: These data indicate that atrasentan modestly improves PCa-specific outcomes relative to placebo. The QOL benefit observed with atrasentan therapy was most apparent in HRPC patients with metastases only to bone. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Abbott Laboratories Abbott Laboratories Abbott Laboratories