Niraparib and abiraterone acetate plus prednisone for HRR-deficient metastatic castration-sensitive prostate cancer: a randomized phase 3 trial

作者：Gerhardt Attard, Neeraj Agarwal, Julie N. Graff, Shahneen Sandhu, Eleni Efstathiou, Mustafa Özgüroğlu, Andrea Juliana Gomes, Karina Vianna, Hong Luo, Geoffrey Gotto, Heather H. Cheng, Won Bae Kim, Carly R. Varela, Daneen Schaeffer, K. Krämer, Susan Li, Benoît Baron, Fei Shen, Suneel Mundle, Sharon McCarthy, David Olmos, Kim N., Dana E. Rathkopf · 发表于：Nature Medicine · 年份：2025 · DOI：10.1038/s41591-025-03961-8 · 被引用次数：62 · 研究领域：Prostate Cancer Treatment and Research、PARP inhibition in cancer therapy、Prostate Cancer Diagnosis and Treatment

Inhibition of poly(ADP-ribose) polymerase (PARP) after relapse on hormone therapy is well established for patients with prostate cancer with homologous recombination repair (HRR) gene alterations, but resistance often develops. We hypothesized that PARP inhibition within 6 months of starting androgen deprivation therapy for metastatic castration-sensitive prostate cancer (mCSPC) could be effective and improve radiographic progression-free survival when added to standard-of-care treatments. The double-blind AMPLITUDE trial evaluated combining niraparib, a potent and specific PARP inhibitor, with abiraterone acetate and prednisone (AAP) versus placebo and AAP in mCSPC with HRR gene alterations. Patients (n = 696) were randomized in a 1:1 ratio (348 per group). Median age was 68 years; 56% had BRCA1 or BRCA2 alterations; 78% had high-volume metastases; and 16% had received docetaxel. The primary endpoint was met, with a significant improvement in radiographic progression-free survival observed first in the BRCA subgroup (median not reached at the time of analysis for the niraparib and AAP group versus 26 months for the AAP group; hazard ratio = 0.52; 95% confidence interval: 0.37-0.72; P < 0.0001) and then in the intention-to-treat population (hazard ratio = 0.63; 95% confidence interval: 0.49-0.80; P = 0.0001). The data for overall survival, a key secondary endpoint, are immature (193/389 events) but favor niraparib (hazard ratio = 0.79 (95% confidence interval: 0.59-1.04); BRC...