KEY TAKEAWAYS
- The NCT02489318 Phase III TITAN study was randomized, double-blind, and placebo-controlled.
- The aim of the study was to determine if a robust prostate-specific antigen (PSA) decline could be achieved with Apalutamide + Androgen Deprivation Therapy (ADT).
- The primary outcome measures of the study were Radiographic Progression-free Survival (rPFS) and Overall Survival (OS) with time frames of up to 35 and 57 months respectively.
- The results of the study confirmed that durable PSA decline improved long-term outcomes in patients with metastatic castration-sensitive prostate cancer.
The first interim analysis of phase III, TITAN study revealed that when Apalutamide was added to ongoing androgen deprivation therapy (ADT), it improved overall survival (OS) and radiographic progression-free survival (rPFS) in patients with metastatic castration-sensitive prostate cancer(mCSPC). The end analysis showed that OS and other long-term outcomes had improved. The study also focused on assessing PSA kinetics and the relationship between PSA decrease and outcomes.
Patients (1:1) were given either a placebo + ADT or Apalutamide (240 mg/day). Using a landmark analysis, Kaplan-Meier method, and Cox proportional-hazards model, this post hoc exploratory analysis assessed PSA kinetics and decline in relation to rPFS (22.7 months’ follow-up) and OS It also studied the time taken for PSA progression and time to castration resistance (44.0 months’ follow-up) in patients with or without confirmed PSA decline.
90%, 73%, and 68% of patients receiving Apalutamide experienced the best verified PSA declines (50% or 90% from baseline or to 0.2 ng/ml), compared to 55%, 29%, and 32% of patients receiving placebo. After 3 months of therapy with Apalutamide, the best deep PSA decline of 90% or to 0.2 ng/ml had been achieved in 59% and 51% of patients receiving Apalutamide, and in 13% and 18% of patients receiving a placebo, respectively.
Deep PSA decline at the landmark of 3 months of Apalutamide treatment was associated with longer OS (HR 0.35; 95% CI 0.25-0.48), prolonged rPFS (0.44; 0.30-0.65), time to castration resistance (0.38; 0.27-0.52), and time to PSA progression (0.31; 0.22-0.44).
Similar outcomes were seen at the crucial 6- and 12-month points in Apalutamide therapy. A robust (rapid, deep, and long-lasting) PSA drop was seen with Apalutamide plus ADT, and this PSA decline was linked to better clinical outcomes, including long-term survival.
Source: https://www.annalsofoncology.org/article/S0923-7534(23)00086-8/fulltext
Clinical Trial: https://clinicaltrials.gov/ct2/show/NCT02489318
Chowdhury, S., Bjartell, A., Agarwal, N., Chung, B. H., Given, R. W., Pereira de Santana Gomes, A. J., Merseburger, A. S., Özgüroğlu, M., Soto, Á. J., Uemura, H., Ye, D., Brookman-May, S. D., Londhe, A., Bhaumik, A., Mundle, S. D., Larsen, J. S., McCarthy, S. A., & Chi, K. N. (2023). 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. Annals of oncology : official journal of the European Society for Medical Oncology, S0923-7534(23)00086-8. Advance online publication. https://doi.org/10.1016/j.annonc.2023.02.009
