Androgen suppression with abiraterone acetate, leuprolide, PARP inhibition, and stereotactic body radiotherapy (ASCLEPIuS) in high-risk and node positive prostate cancer (PCa): Phase I multicenter results.

• DOI: 10.1200/jco.2025.43.5_suppl.387
• Publication Date: 2025-02-18T14:35:11Z
• Authors: William C. Jackson; Robert Timothy Dess; Angela Y Jia; Himanshu Nagar; Neil B Desai; Raquibul Hannan; Jason W.D. Hearn; Zachery R Reichert; Ariel E. Marciscano; Brian Davis; Raed Zuhour; Nicholas G Zaorsky; Jorge A. Garcia; Pedro C. Barata; Jason Robert Brown; Prateek Mendiratta; Felix Y Feng; Arul Chinnaiyan; Krithika Suresh; Daniel Eidelberg ...
• Keywords: Abiraterone acetate; Androgen Suppression; Abiraterone; Enzalutamide

387 Background: Level 1 evidence supports treatment of high-risk and node positive PCa using 4-9 weeks radiotherapy (RT) combined with 18-36 months androgen deprivation therapy (ADT) or without abiraterone acetate plus prednisone (AAP). While effective, some cancers recur, this prolonged is associated inconvenience variable morbidity. We aimed to determine whether the biological synergy stereotactic body (SBRT) a 6-month combination ADT, AAP, PARP inhibitor niraparib, could enable shorter intensified, yet safe therapeutic alternative. Methods: ASCLEPIuS (NCT04194554) multicenter investigator-initiated phase I/II trial in positive, homologous recombination unselected, PCa. Patients received 6 niraparib SBRT prostate (37.5-40 Gy) +/- pelvic lymph nodes (25 Gy). Focal prostate/nodal boosting was permitted. The I primary endpoint maximum tolerated dose (MTD) time-to-event continuous reassessment method (3 levels: 100 mg 200 held during SBRT, concurrent SBRT). Dose limiting toxicities (DLT) were any persistent grade 4+ hematologic toxicity 3+ rectal/urinary at least possibly related as assessed by CTCAE v5.0. Patient reported quality life (QOL) EPIC-26 short form. Linear mixed models used compare scores over time. Results: Accrual began Nov. 2020 transition from II May 2023 after enrolling 54 men. Median follow-up cohort 12.1 (IQR 9.4-18.9), 80% (n=43) had Grade Group 4-5, median PSA 17 ng/mL (range, 1-73), 15% (n=8) cN+ disease, 76% (n=41) nodal RT. There 0 DLTs date, no rectal urinary toxicities, 5 serious adverse events attributable study (anemia, non-rectal gastrointestinal, syncope, infection, musculoskeletal). most common 3 hypertension (n = 11, 21%) leukopenia (n=6, 11%). Transient reductions holds AAP occurred 10 11 patients, respectively. statistically significant declines patient QOL 6- 12-months post-treatment compared baseline (all p >0.15). A transient decline bowel 6-months (p<0.01), which improved (p=0.16). Conclusions: Our findings support short-term safety tolerability nodes, an MTD men completed enrollment 2024, longer-term safety, efficacy, genomic correlations will be presented future. Clinical information: NCT04194554 .