Session: LBA02: Late-Breaking Abstracts II - Cancer
LBA02-11: Updated Progression-Free Survival from PRESTO: a Phase 3 Randomized Study of Androgen Annihilation for High-Risk Biochemically Relapsed Prostate Cancer (AFT-19)
Introduction: In the Phase 3 PRESTO study, intensified androgen deprivation therapy (ADT) with apalutamide (Apa) +/- abiraterone acetate plus prednisone (AAP) administered for 1 year prolonged prostate-specific antigen progression-free survival (PSA-PFS) in patients with high-risk biochemically relapse (BCR). We report PSA-PFS with extended follow up. Methods: PRESTO is a randomized phase 3, open-label trial in patients with BCR following radical prostatectomy and PSADT = 9 months (mo) without distant metastases on conventional imaging (NCT03009981). Patients were randomized 1:1:1 to receive 1 year of ADT, ADT + Apa, or ADT + Apa + AAP, stratified by PSADT ( < 3 vs 3–9 mo). The primary endpoint of PSA-PFS (> 0.2 ng/mL) was compared for each experimental arm vs. control. Analyses were stratified by PSA doubling time and the study was designed to test each hypothesis at a one-sided alpha equal to 0.0125. The first interim analysis at 102 PSA-PFS events in each pair-wise comparison was previously reported (ESMO 2022). We report extended follow up with 146 (ADT vs ADT + Apa) and 142 (ADT vs ADT + Apa + AAP) events, respectively. Results: A total of 504 pts were randomized to ADT (n = 167), ADT + Apa (n = 168) or ADT + Apa + AAP (n = 169). Median time from randomization to last contact was 26.5 and 26.8 months, for the two treatment comparisons. Both experimental arms prolonged PSA-PFS compared to control (Apa + ADT vs ADT HR = 0.59, 97.5% CI: 0.40 – 0.85, 1-sided p-value = 0.0006; ADT + Apa + AAP vs ADT, HR = 0.53, 97.5% CI: 0.36 – 0.77, p-value = 1-sided 0.00006). Median time to testosterone recovery was 3.9, 3.8 and 4.7 mo in ADT, ADT + Apa, and ADT + Apa + AAP arms, respectively. The most common grade = 2 adverse event (AE) was hypertension (19%, 23%, 30% in ADT, ADT + Apa and ADT + Apa + AAP arms, respectively). Three (2.1%) and five (3.4%) patients stopped treatment for AEs in the ADT + Apa and ADT + Apa + AAP arms, respectively. Follow-up for quality of life, metastasis-free survival (MFS), and time to castration resistance (TTCR) is ongoing. Conclusions: In patients with high-risk BCR following radical prostatectomy, intensified ADT with addition of apalutamide or apalutamide plus abiraterone each prolonged biochemical PFS without new safety concerns identified. Follow up is ongoing to determine the impact on longer term endpoints including MFS and time to castration resistance. SOURCE OF Funding: AFT, Janssen; https://acknowledgments.alliancefound.org
