Adding celecoxib with or without zoledronic acid for hormone-naïve prostate cancer: long-term survival results from an adaptive, multiarm, multistage, platform, randomized controlled trial

Mason, M. D. et al. (2017) Adding celecoxib with or without zoledronic acid for hormone-naïve prostate cancer: long-term survival results from an adaptive, multiarm, multistage, platform, randomized controlled trial. Journal of Clinical Oncology, 35(14), pp. 1530-1541. (doi: 10.1200/JCO.2016.69.0677) (PMID:28300506)

Abstract

Purpose: Systemic Therapy for Advanced or Metastatic Prostate Cancer: Evaluation of Drug Efficacy is a randomized controlled trial using a multiarm, multistage, platform design. It recruits men with high-risk, locally advanced or metastatic prostate cancer who were initiating long-term hormone therapy. We report survival data for two celecoxib (Cel)-containing comparisons, which stopped accrual early at interim analysis on the basis of failure-free survival. Patients and Methods: Standard of care (SOC) was hormone therapy continuously (metastatic) or for ≥ 2 years (nonmetastatic); prostate (± pelvic node) radiotherapy was encouraged for men without metastases. Cel 400 mg was administered twice a day for 1 year. Zoledronic acid (ZA) 4 mg was administered for six 3-weekly cycles, then 4-weekly for 2 years. Stratified random assignment allocated patients 2:1:1 to SOC (control), SOC + Cel, or SOC + ZA + Cel. The primary outcome measure was all-cause mortality. Results were analyzed with Cox proportional hazards and flexible parametric models adjusted for stratification factors. Results: A total of 1,245 men were randomly assigned (Oct 2005 to April 2011). Groups were balanced: median age, 65 years; 61% metastatic, 14% N+/X M0, 25% N0M0; 94% newly diagnosed; median prostate-specific antigen, 66 ng/mL. Median follow-up was 69 months. Grade 3 to 5 adverse events were seen in 36% SOC-only, 33% SOC + Cel, and 32% SOC + ZA + Cel patients. There were 303 control arm deaths (83% prostate cancer), and median survival was 66 months. Compared with SOC, the adjusted hazard ratio was 0.98 (95% CI, 0.80 to 1.20; P = .847; median survival, 70 months) for SOC + Cel and 0.86 (95% CI, 0.70 to 1.05; P =.130; median survival, 76 months) for SOC + ZA + Cel. Preplanned subgroup analyses in men with metastatic disease showed a hazard ratio of 0.78 (95% CI, 0.62 to 0.98; P = .033) for SOC + ZA + Cel. Conclusion: These data show no overall evidence of improved survival with Cel. Preplanned subgroup analyses provide hypotheses for future studies.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Russell, Dr Martin and Jones, Professor Robert
• Authors: Mason, M. D., Clarke, N. W., James, N. D., Dearnaley, D. P., Spears, M. R., Ritchie, A. W.S., Attard, G., Cross, W., Jones, R. J., Parker, C. C., Russell, J. M., Thalmann, G. N., Schiavone, F., Cassoly, E., Matheson, D., Millman, R., Rentsch, C. A., Barber, J., Gilson, C., Ibrahim, A., Logue, J., Lydon, A., Nikapota, A. D., O'Sullivan, J. M., Porfiri, E., Protheroe, A., Srihari, N. N., Tsang, D., Wagstaff, J., Wallace, J., Walmsley, C., Parmar, M. K.B., and Sydes, M. R.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: Journal of Clinical Oncology
• Publisher: American Society of Clinical Oncology
• ISSN: 0732-183X
• ISSN (Online): 1527-7755
• Published Online: 13 March 2017
• Copyright Holders: Copyright © 2017 American Society of Clinical Oncology
• First Published: First published in Journal of Clinical Oncology 35(14): 1530-1541
• Publisher Policy: Reproduced under a Creative Commons License