895O - The impact of abiraterone acetate (AA) therapy on patient-reported pain and functional status in chemotherapy-naive patients with progressive, metas...

Date 30 September 2012
Event ESMO Congress 2012
Session Genitourinary tumors, prostate I
Topics Anti-Cancer Agents & Biologic Therapy
Prostate Cancer
Presenter Ethan Basch
Authors E. Basch1, C.J. Ryan2, T. Kheoh3, K. Fizazi4, C.J. Logothetis5, D.E. Rathkopf6, M.R. Smith7, P. Mainwaring8, Y. Hao9, T. Griffin10, S. Li11, M. Meyers12, A. Molina10, C.S. Cleeland13
  • 1Dept. Of Epidemiology & Biostatistics, Memorial Sloan Kettering Cancer Center, 10065 - New York/US
  • 2UCSF, San Francisco/US
  • 3Biostatistics, Janssen Research & Development, Los Angeles/US
  • 4Cancer Medicine, Institut Gustave Roussy, Villejuif/FR
  • 5Department Of Genitourinary Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston/US
  • 6Department Of Medicine, Memorial Sloan-Kettering Cancer Center, 10128 - New York/US
  • 7Hematology-oncology, Massachusetts General Hospital Cancer Center, Boston/US
  • 8Hoca, Hematology & Oncology Clinics of Australia, AU-4101 - Brisbane/AU
  • 9Outcome Research, Janssen Global Services, Raritan/US
  • 10Oncology, Janssen Research & Development, Los Angeles/US
  • 11Biostatistics, Janssen Research & Development, Spring House/US
  • 12Oncology, Janssen Research & Development, Raritan/US
  • 13Symptom Research, MD Anderson Cancer Center, Houston/US

 

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-naïve 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-naïve 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 <0.001 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 < 1 favors AA + P.
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.