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.

The first interim analysis of the phase III, randomized, double-blind, placebo-controlled, multinational TITAN study demonstrated improved overall survival (OS) and radiographic progression-free survival (rPFS) with apalutamide added to ongoing androgen deprivation therapy (ADT) in patients with metastatic castration-sensitive prostate cancer (mCSPC). The final analysis confirmed improvement in OS and other long-term outcomes. We evaluated prostate-specific antigen (PSA) kinetics and the association between PSA decline and outcomes in patients with mCSPC from TITAN.

Patients received apalutamide (240 mg/day) or placebo plus ADT (1:1). This post hoc exploratory analysis evaluated PSA kinetics and decline in relation with 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 using a landmark analysis, Kaplan-Meier method, and Cox proportional-hazards model.

1052 patients (apalutamide, 525; placebo, 527) were enrolled. Best confirmed PSA declines (≥50% or ≥90% from baseline or to ≤0.2 ng/ml ) were achieved at any time during the study in 90%, 73%, and 68% of apalutamide-treated versus 55%, 29%, and 32% of placebo-treated patients. By 3 months of apalutamide treatment, best deep PSA decline of ≥90% or to ≤0.2 ng/ml occurred in 59% and 51% of apalutamide- and in 13% and 18% of placebo-treated patients, respectively. Achievement of deep PSA decline at landmark 3 months of apalutamide treatment was associated with longer OS (HR 0.35; 95% CI 0.25-0.48), rPFS (0.44; 0.30-0.65), time to PSA progression (0.31; 0.22-0.44), and time to castration resistance (0.38; 0.27-0.52) compared with no decline (P < 0.0001 for all). Similar results were observed at landmark 6 and 12 months of apalutamide treatment.

Apalutamide plus ADT demonstrated a robust (rapid, deep, and durable) PSA decline that was associated with improved clinical outcomes, including long-term survival.

Annals of oncology : official journal of the European Society for Medical Oncology. 2023 Feb 27 [Epub ahead of print]

S Chowdhury, A Bjartell, N Agarwal, B H Chung, R W Given, A J Pereira de Santana Gomes, A S Merseburger, M Özgüroğlu, Á Juárez Soto, H Uemura, D Ye, S D Brookman-May, A Londhe, A Bhaumik, S D Mundle, J S Larsen, S A McCarthy, K N Chi

Department of Urological Cancer, Guy's, King's, London, UK; St Thomas' Hospitals, London, UK; Sarah Cannon Research Institute, London, UK. Electronic address: ., Department of Urology, Skåne University Hospital, Lund University, Malmö, Sweden., Department of Genitourinary Oncology, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA., Department of Urology, Yonsei University College of Medicine and Gangnam Severance Hospital, Seoul, South Korea., Department of Urology, Urology of Virginia, Eastern Virginia Medical School, Norfolk, VA, USA., Department of Clinical Oncology, Liga Norte Riograndense Contra O Cancer, Natal, Brazil., Department of Urology, University Hospital Schleswig-Holstein, Campus Lübeck, Lübeck, Germany., Department of Oncology, Cerrahpaşa School of Medicine, Istanbul University-Cerrahpaşa, Istanbul, Turkey., Department of Urology, Hospital Universitario de Jerez de la Frontera, Cadiz, Spain., Department of Medicine, Kindai University Faculty of Medicine, Osaka, Japan., Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China., Janssen Research & Development, Spring House, PA, USA; Ludwig-Maximilians-University (LMU), Munich, Germany., Janssen Research & Development, Titusville, NJ, USA., Janssen Research & Development, Raritan, NJ, USA., Janssen Research & Development, Los Angeles, PA, USA., Department of Medicine, BC Cancer and Vancouver Prostate Centre, Vancouver, BC, Canada.