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

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 survivalwhen added to standard-of-care treatments.

我们假设，在开始雄激素剥夺治疗后的6个月内抑制PARP，对于转移性去势敏感性前列腺癌(mCSPC)患者可能是有效的，并且当添加到标准治疗中时，可以改善放射学无进展生存期。

The double-blindAMPLITUDE 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.

双盲的AMPLITUDE试验评估了将强效且特异性的PARP抑制剂尼拉帕利与阿比特龙醋酸盐和泼尼松（AAP）联合使用，与安慰剂和AAP在携带同源重组修复（HRR）基因改变的转移性去势敏感性前列腺癌（mCSPC）中的效果。

Patients (n = 696) were randomized in a 1:1 ratio (348 per group).

患者（n = 696）按1:1的比例随机分组（每组348人）。

Median age was 68 years; 56% had BRCA1 or BRCA2 alterations; 78% had high-volume metastases; and 16% had received docetaxel.

中位年龄为68岁；56%的患者存在BRCA1或BRCA2突变；78%的患者有高体积转移；16%的患者接受过多西他赛治疗。

The primary endpoint was met, with a significant improvement in radiographic progression-free survivalobserved 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-treatpopulation (hazard ratio= 0.63; 95% confidence interval: 0.49-0.80; P = 0.0001).

主要终点达成，观察到放射影像无进展生存期在BRCA亚组中显著改善（分析时niraparib和AAP组的中位无进展时间未达到，而AAP组为26个月；风险比为0.52；95%置信区间：0.37-0.72；P < 0.0001），随后在意向治疗人群中也观察到类似结果（风险比为0.63；95%置信区间：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); BRCA subgroup: hazard ratio= 0.75 (95% confidence interval: 0.51-1.11)).

总生存（关键次要终点）的数据尚不成熟（共发生193/389事件），但倾向于使用尼拉帕利（风险比=0.79（95%置信区间：0.59-1.04）；BRCA亚组：风险比=0.75（95%置信区间：0.51-1.11））。

Incidenceof grade 3 or 4 adverse events was 75% in the niraparib and AAP group and 59% in the AAP group; most frequent in the niraparib and AAP group were anemia (29%), with 25% of patients requiring a blood transfusion, and hypertension (27%).

3级或4级不良事件的发生率为尼拉帕利和AAP组的75%，AAP组的59%；尼拉帕利和AAP组中最常见的是贫血（29%），有25%的患者需要输血，以及高血压（27%）。

There were 14 treatment-emergent adverse events leading to deaths in the niraparib group and seven in the placebo group.

尼拉帕利组中有14例治疗相关的不良事件导致死亡，在安慰剂组中有7例。

Combining niraparib with AAP significantly improved radiographic progression-free survivalin patients with mCSPC harboring BRCA1/BRCA2 or other HRR gene alterations, suggesting clinical benefit with this combination for these patients.

将尼拉帕利与抗雄激素治疗（AAP）联合使用显著提高了携带BRCA1/BRCA2或其他同源重组修复（HRR）基因改变的转移性去势敏感性前列腺癌（mCSPC）患者的放射影像学无进展生存期，这表明这种联合治疗对这些患者具有临床益处。

ClinicalTrials.gov identifier: NCT04497844 .

临床试验注册号：NCT04497844。