ESMO 2019 — Metastatic castration-resistant prostate cancer: olaparib improves PFS and interim OS in selected patients


  • Jo Whelan
  • Oncology Conference reports
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Takeaway

  • Olaparib significantly improved both PFS and interim overall survival compared with hormonal treatment in metastatic castration-resistant prostate cancer (mCRPC) with genetic alterations related to DNA damage repair.

Why this matters

  • Up to 30% of men with mCRPC have such genetic alterations.
  • Treatment options for mCRPC are limited. This is the first biomarker-selected phase 3 study of a targeted agent to produce positive results in this setting.

Study design

  • Cohort A had alterations in BRCA1, BRCA2, or ATM genes and Cohort B had alterations in any of 12 other genes. All had mCRPC that had progressed on enzalutamide or abiraterone acetate.
  • Patients were randomised (2:1) to olaparib or physician’s choice of enzalutamide or abiraterone acetate (both in addition to prednisone).
  • The primary endpoint was radiographic progression-free survival (rPFS) in Cohort A.
  • Funding: AstraZeneca and MSD.

Key results

  • Median rPFS in Cohort A was 7.39 months with olaparib and 3.55 months with hormonal treatment (hazard ratio [HR] 0.34, 95% CI 0.25-0.47, P
  • Median overall survival (interim analysis) in Cohort A was 18.50 and 15.11 months with olaparib and hormonal treatment respectively (HR 0.64, 95% CI 0.43-0.97, P=0.0173). Survival was also improved in the overall population; improvement was despite crossover to olaparib in the hormone therapy arm in both cohorts.
  • 16.4% of patients discontinued olaparib due to adverse events, compared with 8.5% with hormonal treatment.

Limitations

  • Survival data are not yet mature.

Expert commentary

  • “This truly practice-changing study signifies the beginning of an era of targeted therapy [in this setting],” said Eleni Efstathiou MD, PhD (MD Anderson Cancer Center, Houston, TX), who was the invited discussant and not involved in the study.