Treatment of Metastatic Prostate Cancer with Apalutamide and Leuprolide

Introduction to Therapies

Leuprolide is a gonadotropin-releasing hormone (GnRH) analog that serves as the backbone androgen deprivation therapy (ADT), maintaining castrate serum testosterone levels (<50 ng/dL) in patients with metastatic prostate cancer, as recommended by the National Comprehensive Cancer Network 1, 2

The American Society of Clinical Oncology recommends that patients with metastatic castration-sensitive prostate cancer should receive both leuprolide (or another GnRH analog) and apalutamide together, as the TITAN trial demonstrated that apalutamide 240 mg daily plus ADT significantly improved overall survival compared to ADT alone (82.4% vs 73.5% at 24 months; HR 0.67, P=0.005) 3
Radiographic progression-free survival at 24 months was 68.2% with apalutamide plus ADT versus 47.5% with placebo plus ADT (HR 0.48, P<0.001) 3

The National Comprehensive Cancer Network recommends that if PSA doubling time ≤10 months, continue ADT and add apalutamide 240 mg daily (category 1, preferred option), as apalutamide improved metastasis-free survival from 16.2 to 40.5 months (HR 0.28, P<0.001) 1, 4, 5

Common adverse events to monitor include fatigue (30.4%), hypertension (24.8%), rash (23.8%), diarrhea (20.3%), and weight loss (16.1%) 5
Seizure risk (0.2%): Permanently discontinue if seizure occurs 5