CRPC with bone metastasis: radium-223 adds no benefit to AAP

  • Smith M & et al.
  • Lancet Oncol
  • 6 Feb 2019

  • curated by Deepa Koli
  • Univadis Clinical Summaries
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Takeaway

  • Adding radium-223 to abiraterone acetate+prednisone/prednisolone (AAP) fails to improve symptomatic skeletal event-free survival in patients with castration-resistant prostate cancer (CRPC) and bone metastases vs placebo.
  • Add-on radium-223 increases the frequency of bone fractures.

Why this matters

  • Both AAP and radium-223 are approved in CRPC; based on these findings, a combination of both therapies is not recommended.

Study design

  • Randomized, double-blind, placebo-controlled, phase 3 trial, ERA 223.
  • 806 chemotherapy-naive patients with CRPC and bone metastases were randomly assigned to AAP+radium-223 (n=401) or AAP+placebo (n=405).
  • Funding: Bayer.

Key results

  • Median follow-up, 21.2 months
  • 49% of patients in the AAP+radium-223 group and 47% in the placebo group had ≥1 symptomatic skeletal event or died.
  • In the AAP+radium-223 vs placebo group:
    • Median symptomatic skeletal event-free survival was 22.3 vs 26.0 months (HR, 1.122; P=.2636).
    • Fracture rate (any grade) was 29% vs 11%.
    • Most common grade 3-4 treatment-emergent adverse events (TEAEs) were hypertension (11% vs 13%), fractures (9% vs 3%), and increased alanine aminotransferase concentrations (9% vs 7%).
    • Serious TEAE rate was 41% vs 39%.
    • OS was not significantly different (HR, 1.195; P=.1280)
    • Treatment-related deaths occurred in 2 vs 1 patient.

Limitations

  • Bone mineral density not evaluated.