895O - The Impact of Abiraterone Acetate (AA) Therapy on Patient-Reported Pain and Functional Status in Chemotherapy-Naive Patients with Progressive, Metastatic Castration-Resistant Prostate Cancer (MCRPC)

Abstract

ABSTRACT Background AA is a potent, selective androgen biosynthesis inhibitor. The impact of AA on pain and functional status was prospectively evaluated as part of a large phase 3 trial in asymptomatic/mildly symptomatic, progressive, chemotherapy-naive mCRPC. Material and methods COU-AA-302 is an international, randomized, double-blind study of AA (1 g daily) + prednisone (P; 5 mg twice daily) versus placebo (PL) + P in chemo-naive mCRPC patients (pts) with prior medical/surgical castration and anti-androgen therapy. Pain and functional status were assessed at baseline and throughout study treatment using the BPI-SF and FACT-P questionnaires, respectively. For each measure, clinically significant progression/degradation was evaluated using prespecified definitions. Results 546 pts were randomized to AA + P and 542 to PL + P, with median treatment durations of 13.8 and 8.3 months, respectively. Baseline scores were similar between arms; at baseline, mean worst pain intensity score was 1.2 and mean pain interference score was 0.7 in each arm. AA + P significantly delayed average pain intensity progression, pain interference progression, and degradation in FACT-P total score and most subscales, except the social/family well-being subscale where there was no difference (Table). A post hoc sensitivity analysis using a more stringent definition of worst pain intensity progression (ie, a 2 point worsening at 2 consecutive study visits), showed a significant advantage of AA + P over PL + P at the 25th percentile (median was not reached for this analysis). Conclusions In asymptomatic/minimally symptomatic mCRPC, AA + P delayed functional decline and progression of pain compared to PL + P alone. The extent of these benefits, coupled with improvements in other efficacy end points [Ryan et al ASCO 2012], suggests that AA is a suitable therapy option in this setting. Table: 895O Median time to event, months AA + P (n = 546) PL + P (n = 542) p valuea Hazard ratiob (95% CI) Pain progression Average pain intensityc 26.7 18.4 0.049 0.817 (0.668-0.999) Worst pain intensity (prespecified analysis)c 26.7 19.4 0.109 0.845 (0.688-1.038) Worst pain intensity, 25th percentile (post hoc sensitivity analysis)d 14.8 12.0 0.045 0.777 (0.607-0.995) Pain interference 10.3 7.4 0.005 0.792 (0.674-0.931) Functional status degradation FACT-P total score 12.7 8.3 0.003 0.778 (0.659-0.918) Physical well-being 14.8 11.1 0.002 0.759 (0.637-0.904) Social/Family well-being 18.4 16.6 0.528 0.940 (0.775-1.139) Emotional well-being 22.1 14.2 0.001 0.714 (0.586-0.869) Functional well-being 13.3 8.4 0.001 0.760 (0.644-0.898) Prostate cancer subscale 11.1 5.8 0.703 (0.598-0.827) aObtained from log-rank test stratified by ECOG performance status score (0 or 1). bObtained from stratified proportional hazards model. Hazard ratio cProgression: 30% increase in baseline score without decreased analgesic usage score, at 2 consecutive visits. dProgression: 2-point increase in baseline score without decreased analgesic usage score, at 2 consecutive visits. Disclosure T. Kheoh is an employee of Janssen R&D and holds stock options of Johnson & Johnson. K. Fizazi has the following conflicts of interest to disclose: Honoraria: Janssen Consultancy: Janssen, Cougar Biotechnology Speaker/Advisory Board Participation: Janssen, C.J. Logothetis has received consultancy fees and travel support from Ortho Biotech and research support from Johnson & Johnson, M.R. Smith has served as an advisor to Cougar Biotechnology and Johnson & Johnson and has received research funding from Cougar Biotechnology and Johnson & Johnson. Y. Hao is an employee of Janssen Global Services and holds stock options of Johnson & Johnson. T. Griffin is an employee of Janssen R&D and holds stock options of Johnson & Johnson. S. Li is an employee of Janssen R&D and holds stock options of Johnson & Johnson. M. Meyers is an employee of Janssen R&D and holds stock options of Johnson & Johnson. A. Molina is an employee of Janssen R&D and holds stock options of Johnson & Johnson. All other authors have declared no conflicts of interest.