Darolutamide + Consolidation Radiotherapy in Advanced Prostate Cancer Detected by PSMA

Prior treatment

• Prior treatment with second-generation androgen receptor (AR) antagonists, CYP17 enzyme inhibitors or oral ketoconazole
• Use of oestrogens or 5-α reductase inhibitors or anti-androgens within 28 days before randomisation
• Use of systemic corticosteroid with a dose greater than the equivalent 10 mg of prednisone/day within 28 days before randomisation
• Radiotherapy within 12 weeks prior to randomisation
• Initiation of treatment with an osteoclast-targeted therapy to prevent skeletal-related events within 12 weeks before randomisation
• Any of the following within 6 months before randomisation: stroke, myocardial infarction, severe/unstable angina pectoris, coronary/peripheral artery bypass graft; congestive heart failure New York Heart Association (NYHA) Class III or IV
• Unable to swallow study medications and comply with study requirements

Other illness

• Patients with detectable metastases or a history of metastatic disease on conventional imaging
• Uncontrolled hypertension
• Prior malignancy
• Gastrointestinal disorder or procedure that expects to interfere significantly with the absorption of study treatment

• ≥ 18 years of age and provided written Informed Consent
• Histologically or cytologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation or small cell features
• Castration-resistant prostate cancer, defined as at least 2 consecutive PSA rises obtained at least 1 week apart in the setting of castrate testosterone levels
• Castrate level of serum testosterone (\<1.7 nmol/l \[50 ng/dl\]) on gonadotrophin - releasing hormone (GnRH) agonist or antagonist therapy or after bilateral orchiectomy
• A baseline PSA level of at least 1ng per millilitre and a PSA doubling time of 10 months or less
• Adequate bone marrow reserve and organ function Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• At least 1 site of PSMA-avid disease on PSMA-PET/CT imaging in any of the following regions; At least 1 site of PSMA-avid disease on PSMA-PET/CT imaging in any of the following regions:
  • Local recurrence within the prostate gland or prostate bed
  • Regional lymph node disease (below the aortic bifurcation)
  • Extra-pelvic lymph node, bone or soft tissue metastatic disease