Deep Prostate-specific Antigen Response following Addition of Apalutamide to Ongoing Androgen Deprivation Therapy and Long-term Clinical Benefit in SPARTAN

Background: Apalutamide plus androgen deprivation therapy (ADT) significantly improved metastasis-free survival (MFS), overall survival (OS), and time to prostatespecific antigen (PSA) progression in the placebo-controlled SPARTAN study of highrisk nonmetastatic castration-resistant prostate cancer (nmCRPC). Objective: To assess the relationships between PSA kinetics, outcomes, and molecular subtypes in SPARTAN. Design, setting, and participants: The authors conducted a post hoc analysis of nmCRPC patients randomized to receive apalutamide (n = 806) or placebo (n = 401) plus ADT and a subset stratified by molecular classifiers. Intervention: Apalutamide 240 mg/d. Outcome measurements and statistical analysis: The association between PSA kinetics and MFS, OS, time to PSA progression, and molecular subtypes was evaluated using the landmark analysis and Kaplan-Meier methods. Results and limitations: By 3 mo, PSA decreased in most apalutamide-treated patients and increased in most placebo-treated patients. After apalutamide, the median time to PSA nadir, confirmed >50% PSA reduction, >90% PSA reduction, and PSA <0.2 ng/ml were 7.4, 1.0, 1.9, and 2.8 mo, respectively. By 6 mo, 90%, 57%, and 32% of apalutamide patients had >50% PSA reduction, >90% PSA reduction, and PSA <0.2 ng/ml, respectively,