Darolutamide in Japanese patients with metastatic hormone-sensitive prostate cancer: Phase 3 ARASENS subgroup analysis

Cancer Med. 2024 Nov;13(21):e70029. doi: 10.1002/cam4.70029.

Abstract

Background: In the global ARASENS study (NCT02799602), darolutamide plus androgen-deprivation therapy (ADT) and docetaxel significantly reduced risk of death by 32.5% versus placebo plus ADT and docetaxel (hazard ratio [HR] 0.68; 95% confidence interval [CI] 0.57-0.80; p < 0.0001), with a favorable safety profile in patients with metastatic hormone-sensitive prostate cancer (mHSPC). We investigated outcomes in Japanese participants.

Methods: Patients were randomized 1:1 to oral darolutamide 600 mg twice daily or placebo, plus ADT and docetaxel. The primary endpoint was overall survival.

Results: The Japanese subgroup comprised 148 patients (darolutamide 63, placebo 85). In the Japanese versus overall population, more patients were aged ≥75 years (darolutamide/placebo 35%/22% vs. 16%/17%) and had body mass index <25 kg/m2 (78%/79% vs. 46%/43%), The ECOG performance status 0 (92%/88% vs. 72%/71%), de novo mHSPC (95%/97% vs. 86%/87%), and Gleason score ≥8 (94%/92% vs. 78%/79%). Median treatment duration was 43.3/15.4 months for darolutamide/placebo. The overall survival HR for darolutamide versus placebo was 0.91 (95% CI 0.50-1.64), despite 85% of patients in the placebo group receiving subsequent life-prolonging therapy. Darolutamide prolonged time to castration-resistant prostate cancer (HR 0.31; 95% CI 0.17-0.55). Treatment-emergent adverse event incidences were generally similar between groups. Adverse events known to be associated with docetaxel (e.g., neutropenia) were more frequent in the Japanese versus overall population.

Conclusion: In conclusion, efficacy outcomes showed positive trends for darolutamide plus ADT and docetaxel in Japanese patients with mHSPC, consistent with the overall population, despite higher risk factors. The combination was well tolerated, with no new safety signals in Japanese patients.

Keywords: Japanese; darolutamide; efficacy; metastatic hormone‐sensitive prostate cancer; safety.

Publication types

  • Clinical Trial, Phase III
  • Randomized Controlled Trial
  • Multicenter Study

MeSH terms

  • Aged
  • Aged, 80 and over
  • Androgen Antagonists / administration & dosage
  • Androgen Antagonists / adverse effects
  • Androgen Antagonists / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols* / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols* / therapeutic use
  • Docetaxel* / administration & dosage
  • Docetaxel* / adverse effects
  • Docetaxel* / therapeutic use
  • Double-Blind Method
  • East Asian People
  • Humans
  • Japan
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • Prostatic Neoplasms* / drug therapy
  • Prostatic Neoplasms* / mortality
  • Prostatic Neoplasms* / pathology
  • Pyrazoles / administration & dosage
  • Pyrazoles / adverse effects
  • Pyrazoles / therapeutic use
  • Treatment Outcome

Substances

  • darolutamide
  • Docetaxel
  • Pyrazoles
  • Androgen Antagonists