Choosing Between Abiraterone and Darolutamide for High-Volume mHSPC

Introduction to Treatment Options

The National Comprehensive Cancer Network recommends triplet therapy with ADT + docetaxel + darolutamide or ADT + docetaxel + abiraterone as the preferred choice for patients with high-volume metastatic hormone-sensitive prostate cancer who are fit for chemotherapy, based on robust survival data from ARASENS and PEACE-1, respectively 1, 2.

The PEACE-1 trial demonstrated a 1-year overall survival gain (HR 0.75; 95% CI 0.59-0.95) in the triplet arm versus ADT + docetaxel for de novo metastatic patients 3, 1.
The ARASENS trial showed a 2-year overall survival improvement with 4-year OS of 62.7% versus 50.4% (HR 0.68; 95% CI 0.57-0.80) for patients with high-volume metastatic hormone-sensitive prostate cancer 1, 4, 5.

Both triplet regimens are NCCN Category 1, preferred options for patients with metastatic castration-sensitive prostate cancer, with use strongly encouraged for high-volume de novo disease in chemotherapy-fit patients 3, 1.
The 2023 NCCN Guidelines prioritize triplet therapies over doublet therapy (ADT + docetaxel alone) for high-volume disease, as both PEACE-1 and ARASENS demonstrated superior overall survival compared to ADT + docetaxel 3, 1.

High-volume disease (visceral metastases or ≥4 bone lesions with ≥1 beyond vertebral bodies/pelvis) is a key consideration for triplet therapy 1.
For abiraterone + prednisone, monthly monitoring of liver function tests, serum potassium, phosphate levels, and blood pressure is recommended 8, 6, 7.
For darolutamide, serial PSA every 3-6 months and conventional imaging every 6-12 months are recommended 5.

Abiraterone demonstrates measurable QoL benefits with 37% risk reduction in pain intensity progression, 53% reduction in fatigue, and 15% reduction in overall QoL deterioration compared to ADT alone 9.
Darolutamide shows favorable tolerability with lower discontinuation rates due to adverse events and lower fatigue incidence than placebo 5.

ADT + docetaxel doublet therapy alone is considered suboptimal for high-volume mHSPC when patients are fit for triplet therapy 3, 1.
Switching between abiraterone formulations or between abiraterone with different steroids upon disease progression is not recommended 6.
Avoiding corticosteroids with abiraterone without careful monitoring and readiness to add mineralocorticoid receptor antagonist or steroid is not recommended 6.
Repeating the same novel hormonal therapy after progression is not recommended, with the exception of docetaxel rechallenge after progression on a novel hormone therapy if docetaxel was given in the castration-naive setting 10.