To assess the association between achievement of prostate-specific antigen (PSA) levels ≤0.2 ng/mL (henceforth 'ultralow') and clinical outcomes in patients in the 'Targeted Investigational Treatment Analysis of Novel Anti-androgen' (TITAN) study (ClinicalTrials. gov Identifier NCT02489318) with metastatic castration-sensitive prostate cancer (mCSPC).
Patients in the TITAN study with mCSPC were randomised to 240 mg/day apalutamide (n = 525) or placebo (n = 527) plus androgen-deprivation therapy. This post hoc analysis assessed the achievement of a PSA level of 0.2->0.02 ng/mL ('ultralow one' [UL1]) and ≤0.02 ng/mL ('ultralow two' [UL2]) vs >0.2 ng/mL with apalutamide treatment and its association with radiographic progression-free survival (rPFS), overall survival (OS), time to castration-resistant PC (TTCRPC), and time to PSA progression (TTPP). The landmark analysis and Kaplan-Meier methods were used.
By 3 months, more patients achieved UL1 and UL2 with apalutamide (38% and 23%) vs placebo (15% and 5%). In the apalutamide-treated patients, UL2 vs PSA >0.2 ng/mL at landmark 3 months was associated with significantly longer rPFS (hazard ratio [HR] 0.28, 95% confidence interval [CI] 0.14-0.54), OS (HR 0.24, 95% CI 0.13-0.43), TTCRPC (HR 0.2, 95% CI 0.11-0.38), and TTPP (HR 0.11, 95% CI 0.04-0.27; nominal P values all <0.001); this association was also observed but less pronounced for UL1. Similar findings were observed at 6 months. Early onset of decline to UL2 by 3 months was associated with improved survival vs PSA >0.2 ng/mL anytime (HR 0.12, 95% CI 0.06-0.22; P < 0.001) in apalutamide-treated patients.
In this post hoc analysis of TITAN, patients with the deepest PSA decline derived the greatest benefit. These results extend our findings of apalutamide efficacy in the overall TITAN population, underscoring the clinical value of PSA kinetics as a marker for treatment efficacy.
Patients with metastatic prostate cancer that is sensitive to ongoing hormonal treatment benefited significantly from the addition of apalutamide compared with placebo. Those who achieved rapid and deep PSA reduction had the greatest survival benefit.
BJU international. 2024 Jun 28 [Epub ahead of print]
Axel S Merseburger, Neeraj Agarwal, Anders Bjartell, Hirotsugu Uemura, Alvaro Juarez Soto, Amitabha Bhaumik, Jürgen Böhm, Nguyen Tran, Nils Krochmann, Mehregan Nematian-Samani, Suneel D Mundle, Sabine D Brookman-May, Angela Lopez-Gitlitz, Sharon A McCarthy, Kim Chi, Simon Chowdhury
Department of Urology, University Hospital Schleswig-Holstein, Campus Lübeck, Lübeck, Germany., Department of Genitourinary Oncology, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA., Department of Urological Cancer, Skåne University Hospital, Lund University, Malmö, Sweden., Department of Urology, Kindai University Faculty of Medicine, Osaka, Japan., Department of Urology, Hospital Universitario de Jerez de la Frontera, Cadiz, Spain., Janssen Research and Development, Titusville, NJ, USA., Janssen-Cilag GmbH, Neuss, Germany., Janssen Research and Development, Raritan, NJ, USA., Ludwig-Maximilians-University, Munich, Germany., Janssen Research & Development, Los Angeles, CA, USA., Department of Medicine, BC Cancer and Vancouver Prostate Centre, Vancouver, British Columbia, Canada., Department of Urological Cancer, Guy's, King's, and St. Thomas' Hospitals and Sarah Cannon Research Institute, London, UK.