Metastatic prostate cancer: increased, extended radium-223 dose schedule fails phase 2

  • Sternberg CN & al.
  • Ann Oncol
  • 1 Feb 2020

  • curated by Deepa Koli
  • Univadis Clinical Summaries
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Takeaway

  • Higher or extended dosing schedules of radium-223 fail to extend symptomatic skeletal events-free survival (SSE-FS) in patients with metastatic castration-resistant prostate cancer (mCRPC) and bone metastases vs standard dose and schedule (55 kBq/kg; 6 cycles).

Why this matters

  • 2 previous phase 2 studies have reported dose-dependent effects on serum markers, increased disease control, and pain relief.
  • But current results support 6 injections of standard-dose radium-223 as the optimal regimen.

Study design

  • Phase 2: 391 patients with mCRPC and bone metastases were randomly assigned 1:1:1 to radium-223 standard dose and schedule, high dose (88 kBq/kg; 6 cycles), or extended schedule (55 kBq/kg; 12 cycles).
  • Funding: Bayer.

Key results

  • SSE rates:
    • 28% standard dose.
    • 32% high dose.
    • 37% extended schedule.
  • Median SSE-free survival did not differ significantly between:
    • High- vs standard-dose groups:
      • 12.9 vs 12.3 months;
      • HR, 1.06 (P=.70).
    • Extended- vs standard-schedule groups:
      • 10.8 vs 13.2 months;
      • HR, 1.26 (P=.31). 
  • OS (HRs) was similar between:
    • High- vs standard-dose groups: 1.08 (P=.62);
    • Extended-schedule vs standard-schedule groups: 1.00 (P=1.00).
  • Most common grade ≥3 adverse event was anemia:
    • 10% standard, 14% high, 14% extended.
  • Serious adverse event rates: 20% standard, 29% high, 31% extended.
  • Treatment-discontinuation rates: 33% standard, 46% high, 76% extended.

Limitations

  • Open-label design.