Real-World Evidence of Triplet Therapy in Metastatic Hormone-Sensitive Prostate Cancer: An Austrian Multicenter Study

Area of Science:

• Oncology
• Urology
• Pharmacology

Background:

• Randomized trials established triplet therapy (androgen deprivation therapy [ADT] + androgen receptor pathway inhibitor [ARPI] + docetaxel) as superior to doublet therapy (ADT + docetaxel) for metastatic hormone-sensitive prostate cancer (mHSPC).
• This led to a shift in treatment paradigms for mHSPC.

Purpose of the Study:

• To conduct the first real-world analysis of triplet therapy in mHSPC patients.
• To evaluate treatment patterns, effectiveness, and safety in a real-world Austrian cohort.

Main Methods:

• A retrospective analysis of 97 mHSPC patients from 16 Austrian centers.
• Data collected on baseline characteristics, treatment parameters, and outcomes.
• Statistical analysis included Mann-Whitney U test, X²-test, and logistic regression for progression variables.

Main Results:

• Triplet therapy was primarily used for synchronous, high-volume mHSPC.
• Non-simultaneous initiation of chemotherapy and ARPI (44.3%) was linked to worse treatment response (HR 0.245, P = .015).
• Starting ARPI before chemotherapy increased progression risk (HR 15.781, P = .023). Adverse events occurred in 61.9% of patients (grade 3-5 in 15%).
• All patients achieved PSA decline (99%); imaging response was 88% for abiraterone and 75% for darolutamide.

Conclusions:

• Triplet therapy is effective and tolerable in real-world mHSPC practice, particularly for synchronous high-volume disease.
• Simultaneous administration of chemotherapy and ARPI is preferred.
• If not simultaneous, initiating chemotherapy before ARPI is recommended for better outcomes.