Deep prostate-specific antigen (PSA) decline among early participants (pts) in LIBERTAS, a phase 3 study of apalutamide (APA) plus continuous versus intermittent androgen deprivation therapy (ADT) in metastatic castration-sensitive prostate cancer (mCSPC).
Authors: Arun Azad, Marco Antonio Badillo, Qiang Dong, Alicia K. Morgans, Dana Rathkopf, Karie Runcie, Tian Zhang, Geoffrey Gotto, Axel Stuart Merseburger, Alex Dos Santos, Sukie Shopeju, Amitabha Bhaumik, Suneel Dinkar Mundle, Sharon McCarthy, Neeraj Agarwal
Journal: Journal of Clinical Oncology (2025)

147 Background: LIBERTAS is investigating APA in combination with intermittent ADT as an ADT de-escalation strategy for patients with mCSPC. The objective is to evaluate whether APA + intermittent ADT in pts who achieved PSA &lt;0.2 ng/mL after 6 mo initial treatment with APA + ADT provides noninferior radiographic progression-free survival (rPFS) and reduces hot ﬂash burden compared with APA + continuous ADT. In the TITAN study, 54% (263/490) of pts with mCSPC treated with APA + ADT achieved PSA ≤0.2 ng/mL within 3 mo (1). Pts who also achieved PSA ≤0.02 ng/mL vs PSA &gt;0.2 ng/mL showed better overall survival rates (2). Here, we present initial findings of pts enrolled early in LIBERTAS. Methods: LIBERTAS enrolled pts with mCSPC, inclusive of all gender identities. Eligible pts have ≤3 mo ADT prior to enrollment, except for pts receiving ADT as part of their gender-affirming care (GAC), and ECOG PS 0 or 1. Pts have metastasis documented by conventional imaging (CT, MRI, or bone scan) and/or regional lymph node metastases by next-generation imaging (NGI); pts undergoing GAC are eligible with or without evidence of metastasis by conventional imaging or NGI. In the initial 6-mo treatment phase, all pts receive APA 240 mg/d + ADT. In the main treatment phase, 240 pts with confirmed PSA &lt;0.2 ng/mL after the initial treatment phase will be randomized 1:1 to APA 240 mg/d + intermittent or continuous ADT. Stratification: tumor volume and prior treatment for localized PC. Primary end points: rPFS, measured by 18-mo event-free survival rate, and reduction of hot flash burden, measured by the severity-adjusted hot flash score. Results: As of September 20, 2024, 420 pts at 73 sites in 9 countries have enrolled in the initial treatment phase, completing the enrollment goal ahead of schedule. Demographics include 70.5% White, 9.5%, Asian, and 8.6% Black. At baseline, pts had a median (range) age of 70 yrs (48-88) and median PSA 15.0 ng/mL (0.02-6000 ng/mL). At data cutoff, 87 pts had been randomized to the main treatment phase. Among 350 pts with at least 2 evaluable PSA values collected during the initial treatment phase, 246 (70.3%) achieved PSA &lt;0.2 ng/mL and 307 (87.7%) experienced ≥90% PSA decline from baseline at some point during the initial treatment phase. Hot flash compliance, defined as the percentage of data collected per protocol across all sites and visits, exceeded 80%. No new safety signals were observed. Conclusions: Treatment with 6 mo of APA + ADT in this prospective trial resulted in deep PSA responses in the majority of pts with mCSPC. The LIBERTAS study remains on track for successful completion of expected randomization for the standard APA + ADT vs APA + ADT de-escalation. 1. Chowdhury, Ann Oncol 2023. 2. Merseburger, BJU Int 2024. Clinical trial information: NCT05884398 .