Phase 3 AMPLITUDE trial: Niraparib (NIRA) and abiraterone acetate plus prednisone (AAP) for metastatic castration-sensitive prostate cancer (mCSPC) patients (pts) with alterations in homologous recombination repair (HRR) genes.

作者：Gerhardt Attard, Neeraj Agarwal, Julie N. Graff, Shahneen Sandhu, Eleni Efstathiou, Mustafa Özgüroğlu, Andrea Juliana Gomes, Karina Costa Maia Vianna, Hong Luo, Heather H. Cheng, Won Bae Kim, Carlos Federico Varela, Daneen Schaeffer, Shiva Dibaj, Susan Li, Fei Shen, Suneel Mundle, David Olmos, Kim N., Dana E. Rathkopf, on behalf of the AMPLITUDE Investigators · 发表于：Journal of Clinical Oncology · 年份：2025 · DOI：10.1200/jco.2025.43.17_suppl.lba5006 · 被引用次数：21 · 研究领域：Prostate Cancer Treatment and Research、PARP inhibition in cancer therapy、Radiopharmaceutical Chemistry and Applications

LBA5006 Background: NIRA is a highly selective and potent inhibitor of poly (ADP-ribose) polymerase (PARP)-1/2. In the MAGNITUDE trial, NIRA + AAP significantly improved radiographic progression-free survival (rPFS) in HRR gene–altered metastatic castration-resistant prostate cancer. The double-blind, placebo (PBO)-controlled AMPLITUDE trial (NCT04497844) evaluated the efficacy and safety of NIRA + AAP in HRR gene–altered mCSPC. Methods: Pts with germline or somatic HRR gene alterations ( BRCA1 , BRCA2 , BRIP1 , CDK12 , CHEK2 , FANCA , PALB2 , RAD51B , RAD54L ) were randomized 1:1 to a dual-action tablet (NIRA 200 mg + abiraterone acetate 1000 mg) plus prednisone 5 mg, or PBO + AAP (hereafter AAP). Eligible pts had received ≤6 mo of androgen deprivation therapy (ADT) ± ≤6 cycles of docetaxel (DOC) ± ≤45 d of AAP with metastatic disease extended beyond lymph nodes. The primary end point is investigator-assessed rPFS (time from randomization to radiographic progression or death). Secondary end points include time to symptomatic progression (TSP), overall survival (OS), and safety. The Kaplan-Meier product limit method and a stratified Cox model were used for time-to-event variables and the hazard ratio (HR) and stratified log-rank test for estimating treatment effect. This is the first and final analysis for rPFS and the first interim analysis (of 3) for OS (data cutoff, 7 Jan 2025). Approximately 261 rPFS events were required (2-sided α, 0.025; power, 91%) for an HR ≤0.64 to d...