The following is a summary of “Deep, rapid, and durable prostate-specific antigen decline with apalutamide plus androgen deprivation therapy is associated with longer survival and improved clinical outcomes in TITAN patients with metastatic castration-sensitive prostate cancer,” published in the May 2023 issue of the Oncology by Chowdhury et al.

Patients with metastatic castration-sensitive prostate cancer had improved overall survival (OS) and radiographic progression-free survival (rPFS) when apalutamide was added to ongoing androgen deprivation therapy (ADT). The final analysis confirmed the enhancement of OS and other long-term outcomes. Researchers evaluated the kinetics of prostate-specific antigen (PSA) and the relationship between PSA decline and survival in TITAN patients with metastatic castration-sensitive prostate cancer. Patients were administered apalutamide (240 mg/day) or placebo in conjunction with ADT (1:1). 

This post hoc exploratory analysis assessed PSA kinetics and decline about rPFS (22.7 months follow-up) and OS, time to PSA progression, and time to castration resistance (44.0 months follow-up) in patients with or without confirmed PSA decline utilizing landmark analysis, the Kaplan–Meier method, and Cox proportional hazards regression. About 1,052 patients were enrolled (525 on apalutamide and 527 on placebo). Around 90%, 73%, and 68% of apalutamide-treated patients attained best confirmed PSA declines (≥50% or ≥90% from baseline or to ≤0.2 ng/ml) at any time during the study, compared to 55%, 29%, and 33% of placebo-treated patients, respectively. About 59% and 51% of apalutamide-treated patients achieved the highest deep PSA decline of ≥90% or ≤0.2 ng/ml at 3 months, compared to 13% and 18% of placebo-treated patients, respectively. 

Deep PSA decline at 3 months was associated with longer OS [hazard ratio (HR) 0.35; 95% CI 0.25 to 0.48], rPFS (HR 0.44; 95% CI 0.30-0.65), time to PSA progression (HR 0.31; 95% CI 0.22-0.44) and time to castration resistance (HR 0.38; 95% CI 0.27-0.52) compared with no decline (P<0.0001 for all). Similar outcomes were observed at the 6-month and 12-month milestones of apalutamide treatment. Combining apalutamide and androgen deprivation therapy (ADT) was associated with enhanced clinical outcomes, including more prolonged survival.

Source: sciencedirect.com/science/article/pii/S0923753423000868