Validation of prostate-specific antigen (PSA) decline among the Latin American subgroup of LIBERTAS: A phase 3 study of apalutamide (APA) plus continuous versus intermittent androgen deprivation therapy (ADT) in metastatic castration-sensitive prosta

5021 Background: APA in combination with continuous ADT showed rapid and deep PSA decline in participants (pts) with mCSPC in the TITAN study, and this deep PSA decline was associated with improved overall survival. LIBERTAS (NCT05884398), a global phase 3 study, is evaluating APA + intermittent ADT as an ADT de-escalation strategy for pts with mCSPC who achieve an undetectable PSA ( < 0.2 ng/mL) after 6 months on APA + ADT. In the initial treatment phase of LIBERTAS, 6 months of APA + continuous ADT resulted in deep PSA responses in the majority of pts with mCSPC. Methods: Pts with mCSPC were eligible if they had ≤3 months of prior ADT, ECOG PS 0–1 and confirmed metastases by conventional or next-generation imaging. In the initial 6-month treatment phase, all pts received APA 240 mg/day + ADT. In the main treatment phase, pts with < 0.2 ng/mL were randomized 1:1 to APA 240 mg/day + intermittent or continuous ADT. Co-primary endpoints were radiographic progression-free survival (rPFS), measured by the 18-month event-free survival rate, and reduction of hot flash burden, measured by the 18-month severity-adjusted hot flash score. Here, we present an analysis of the Latin American (LATAM) subgroup evaluating PSA response results following the initial treatment phase. Results: From Dec 2023 to July 2024, 118 LATAM pts were enrolled (87 pts from 7 sites in Brazil, and 31 pts from 4 sites in Mexico). Racial distribution in LATAM pts was 60.2% White, 10.2% Black, 9.3% Multiple, and 17.8% other. LATAM pts were younger (median age 67 years [range: 48–86]) and had more advanced disease (89.0% with M1 disease at diagnosis; 39.8% with ECOG PS 1, 66.1% with high volume disease; median baseline PSA 22.95 ng/mL [IQR: 3.18–87.00]) compared with the overall study population. Among 109 pts who completed the 6-month initial treatment phase, 104 (95.4%) achieved a ≥50% PSA decline (PSA50), 90 (82.6%) achieved a ≥90% decline (PSA90), and 66 (60.6%) achieved PSA < 0.2 ng/mL (PSA0.2), of which 62 (56.9%) pts were randomized to the main treatment phase. Median time to response was 1.87 months for PSA50, 1.91 months for PSA90, and 3.14 months for PSA0.2. No new safety signals were observed in the LATAM subgroup. Conclusions: LATAM pts in LIBERTAS were younger on average and had more advanced disease compared with the overall study population. Despite having higher baseline PSA levels, LATAM pts with mCSPC demonstrated rapid and deep PSA responses to APA + ADT, consistent with the results from the global analysis. The safety profile of APA was consistent with previous studies. The LIBERTAS study remains on track for the primary readout. Clinical trial information: NCT05884398 .