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

STAMPEDE investigators

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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.

Original languageEnglish
Pages (from-to)1530-1541
Number of pages12
JournalJournal of Clinical Oncology
Volume35
Issue number14
Early online date13 Mar 2017
DOIs
Publication statusPublished - 10 May 2017

Bibliographical note

Funding Information:
Supported by the Cancer Research UK, Medical Research Council, Novartis, Sanofi,Pfizer, Janssen Pharmaceuticals, Astellas Pharma, National Institute of Health Research Clinical Research Network (formerly National Cancer Research Network), and the Swiss Group for Clinical Cancer Research. Research Funding: Janssen (Inst), Astellas Pharma (Inst), Pfizer (Inst), Sanofi (Inst), Novartis (Inst) Research Funding: Takeda Pharmaceuticals Research Funding: Sanofi, Novartis, Pfizer, Janssen Pharmaceuticals, Astellas Pharma Research Funding: Janssen Pharmaceuticals (Inst), AstraZeneca (Inst), Arno Therapeutics (Inst), Innocrin Pharma (Inst) Research Funding: Novartis, Pfizer (Ins) Research Funding: Bayer Schering Pharma (Inst) Research Funding: Pfizer (Inst) Research Funding: Bayer AG Research Funding: Novartis Research Funding: Novartis (Inst) Research Funding: Novartis, Sanofi, Pfizer, Janssen Pharmaceuticals, Astellas Pharma Research Funding: Astellas Pharma, Janssen-Cilag, Pfizer, Novartis, Sanofi, Clovis Oncology D.P.D., C.C.P., and G.A. acknowledge support from the NIHR to the Royal Marsden NHS Trust and The Institute of Cancer Research Biomedical Research Centre

Publisher Copyright:
© 2017 by American Society of Clinical Oncology.

Copyright:
Copyright 2019 Elsevier B.V., All rights reserved.

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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