Castration-resistant prostate cancer: what is the optimal abiraterone-enzalutamide sequence?

  • Khalaf DJ & et al.
  • Lancet Oncol
  • 11 Nov 2019

  • curated by Deepa Koli
  • Univadis Clinical Summaries
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Takeaway

  • In patients with metastatic castration-resistant prostate cancer (mCRPC), the treatment sequence of abiraterone+prednisone followed by enzalutamide shows a longer time to PSA progression and higher proportion of patients with PSA response vs the opposite treatment sequence.

Why this matters

  • This is the first randomized, head-to-head comparison of abiraterone+prednisone and enzalutamide.
  • Second-line enzalutamide can be considered an appropriate treatment option at first progression with abiraterone+prednisone.

Study design

  • Phase 2 study of 202 patients with mCRPC, randomly assigned 1:1 to abiraterone+prednisone followed by crossover to enzalutamide at PSA progression (abiraterone-enzalutamide group) or vice versa (enzalutamide-abiraterone group).
  • Funding: Canadian Cancer Society Research Institute; others.

Key results

  • The median follow-up, 30.7 months.
  • Primary endpoints: in the abiraterone-enzalutamide vs enzalutamide-abiraterone group:
    • The median time to second PSA progression was 19.3 vs 15.2 months (HR, 0.66; P=.36). 
    • 36% vs 4% of patients showed PSA responses (P<.0001 prespecified psa decline threshold for activity was>
  • Time to PSA progression was not statistically different after first-line treatment (HR, 0.95; P=.78).
  • PSA response was seen in 68% of patients with first-line abiraterone and 82% of patients with first-line enzalutamide.
  • Serious adverse events rate was 15% with abiraterone+prednisone and 20% with enzalutamide-abiraterone sequence.
  • The most common grade 3-4 adverse events: hypertension and fatigue.

Limitations

  • Open-label study.