Saad F, Small EJ, Feng FY, et al. - In nonmetastatic castration-resistant prostate cancer (nmCRPC) patients, treatment with apalutamide plus androgen deprivation therapy (ADT) resulted in rapid, deep, and durable prostate-specific antigen (PSA) responses by 6-mo treatment irrespective of evaluated molecular prognostic markers. Clinical benefits were obtained in relation to an early PSA response with apalutamide, supporting prognostic value of PSA monitoring.

• In the placebo-controlled SPARTAN study, significant improvements in metastasis-free survival (MFS), overall survival (OS), and time to PSA progression were achieved with apalutamide plus ADT in high-risk nmCRPC.

• This is 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, to examine the links between PSA kinetics, outcomes, and molecular subtypes in SPARTAN.

• By 3 mo, PSA reduced in the majority of apalutamide-treated patients and rose in most placebo-treated cases.

• Post-apalutamide treatment, the median time to PSA nadir, corroborated ≥50% PSA decrease, ≥90% PSA decrease, 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 were found to have ≥50% PSA decrease, ≥90% PSA decrease, and PSA ≤0.2 ng/ml, respectively, while only 1.5% of placebo patients had ≥50% PSA decrease.

• Reductions in PSA were noted within 3 mo and up to 12 mo of apalutamide therapy, and were similar across molecular subtypes.

• At landmark 6-mo apalutamide treatment, deep PSA responses (≥90% PSA reduction or PSA ≤0.2 ng/ml) were identified to be significantly related to improved time to PSA progression, MFS, and OS.