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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, Malcolm D. Clarke, Noel W. James, Nicholas D. Dearnaley, David P. Spears, Melissa R. Ritchie, Alastair W.S. Attard, Gerhardt Cross, William Jones, Rob J. Parker, Christopher C.
Mason, Malcolm D.
Clarke, Noel W.
James, Nicholas D.
Dearnaley, David P.
Spears, Melissa R.
Ritchie, Alastair W.S.
Attard, Gerhardt
Cross, William
Jones, Rob J.
Parker, Christopher C.
Authors
Mason, Malcolm D.
Clarke, Noel W.
James, Nicholas D.
Dearnaley, David P.
Spears, Melissa R.
Ritchie, Alastair W.S.
Attard, Gerhardt
Cross, William
Jones, Rob J.
Parker, Christopher C.
Russell, J. Martin
Thalmann, George N.
Schiavone, Francesca
Cassoly, Estelle
Matheson, David
Millman, Robin
Rentsch, Cyrill A.
Barber, Jim
Gilson, Clare
Ibrahim, Azman
Logue, John
Lydon, Anna
Nikapota, Ashok D.
O’Sullivan, Joe M.
Porfiri, Emilio
Protheroe, Andrew
Srihari, Narayanan Nair
Tsang, David
Wagstaff, John
Wallace, Jan
Walmsley, Catherine
Parmar, Mahesh K.B.
Sydes, Matthew R.
Clarke, Noel W.
James, Nicholas D.
Dearnaley, David P.
Spears, Melissa R.
Ritchie, Alastair W.S.
Attard, Gerhardt
Cross, William
Jones, Rob J.
Parker, Christopher C.
Russell, J. Martin
Thalmann, George N.
Schiavone, Francesca
Cassoly, Estelle
Matheson, David
Millman, Robin
Rentsch, Cyrill A.
Barber, Jim
Gilson, Clare
Ibrahim, Azman
Logue, John
Lydon, Anna
Nikapota, Ashok D.
O’Sullivan, Joe M.
Porfiri, Emilio
Protheroe, Andrew
Srihari, Narayanan Nair
Tsang, David
Wagstaff, John
Wallace, Jan
Walmsley, Catherine
Parmar, Mahesh K.B.
Sydes, Matthew R.
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2017-03-13
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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.
Citation
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.
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Journal article
Language
en
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0732-183X
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The Medical Research Council sponsored the study and was involved in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, and approval of the manuscript. Funding was also provided by Cancer Research UK, Astellas, Janssen, Novartis, Sanofi-Aventis, and Pfizer, none of which were directly involved in the research