PARP and Androgen-Signaling Inhibition plus ADT in Metastatic Prostate Cancer.

Methods

In this ongoing, phase 3, double-blindtrial assessing talazoparib in patients with metastatic androgen pathway modulation-sensitive [APMS] prostate cancer harboring alterations in homologous recombination repair genes, we randomly assigned patients in a 1:1 ratio to receive talazoparib at a dose of 0.5 mg plus enzalutamide at a dose of 160 mg once daily (talazoparib group) or placebo plus enzalutamide at a dose of 160 mg once daily (control group).

在这项正在进行的、第3阶段、双盲试验中，我们评估了在携带同源重组修复基因改变的转移性雄激素途径调节敏感性[APMS]前列腺癌患者中使用talazoparib的效果，我们以1:1的比例随机分配患者接受每日一次0.5毫克talazoparib加160毫克enzalutamide（talazoparib组）或安慰剂加160毫克enzalutamide（对照组）。

Randomization was stratified according to disease status (new or relapsed), disease volume (high or low), and BRCA (vs. non-BRCA) mutation status.

随机化根据疾病状态（新发或复发）、疾病体积（高或低）以及BRCA（与非BRCA）突变状态进行了分层。

The primary end point was investigator-assessed imaging-based progression-free survival. The key secondary end point was overall survival.

主要终点是研究者评估的基于影像学的无进展生存期。关键次要终点是总生存期。

Results

A total of 300 patients were assigned to the talazoparib group and 299 to the control group.

共有300名患者被分配到talazoparib组，299名患者被分配到对照组。

At 3 years, progression-free survivalwas 77% in the talazoparib group and 56% in the control group (hazard ratiofor disease progression or death, 0.48; 95% confidence interval[CI], 0.36 to 0.65; P<0.001).

在3年时，talazoparib组的无进展生存率为77%，对照组为56%（疾病进展或死亡的风险比为0.48；95%置信区间[CI]，0.36至0.65；P<0.001）。

In this interim analysis, overall survivalat 3 years was 78% in the talazoparib group and 72% in the control group (hazard ratiofor death, 0.77; 95% CI, 0.56 to 1.04).

在这次中期分析中，talazoparib组和对照组的3年总生存率分别为78%和72%（死亡风险比为0.77；95%置信区间，0.56至1.04）。

Serious adverse events were reported in 42% and 32% of the patients in the talazoparib group and the control group, respectively.

在talazoparib组和对照组中，分别有42%和32%的患者报告了严重不良事件。

In the talazoparib group, the most common adverse events were anemia, fatigue, and decreased neutrophil count, and the most common event of grade 3 or higher was anemia, reported in 51% of the patients; two treatment-related deaths occurred.

在接受talazoparib治疗的组别中，最常见的不良事件为贫血、疲劳及中性粒细胞减少，而3级或更高级别的最常见不良事件为贫血，51%的患者报告了此情况；发生了两例与治疗相关的死亡事件。

Conclusions

Talazoparib added to enzalutamide led to significantly better imaging-based progression-free survivalthan placebo plus enzalutamide among patients with metastatic APMS prostate cancer harboring alterations in homologous recombination repair genes.

在携带同源重组修复基因突变的转移性APMS前列腺癌患者中，将talazoparib与enzalutamide联合使用相较于安慰剂加enzalutamide，显著提高了基于影像学的无进展生存期。

Serious adverse events were more common with talazoparib plus enzalutamide than with placebo plus enzalutamide.

与安慰剂加恩杂鲁胺相比，talazoparib加恩杂鲁胺的严重不良事件更为常见。

(Funded by Pfizer; TALAPRO-3 ClinicalTrials.gov number, NCT04821622.).

(由辉瑞资助；TALAPRO-3临床试验注册号，NCT04821622。)