尼拉帕利与醋酸阿比特龙治疗转移性去势抵抗性前列腺癌。

Niraparib and Abiraterone Acetate for Metastatic Castration-Resistant Prostate Cancer.

机构信息

BC Cancer - Vancouver Center, University of British Columbia, Vancouver, BC, Canada.

Memorial Sloan Kettering Cancer Center and Weill Cornell Medicine, New York, NY.

出版信息

J Clin Oncol. 2023 Jun 20;41(18):3339-3351. doi: 10.1200/JCO.22.01649. Epub 2023 Mar 23.

DOI:10.1200/JCO.22.01649

PMID:36952634

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10431499/

Abstract

PURPOSE

Metastatic castration-resistant prostate cancer (mCRPC) remains a lethal disease with current standard-of-care therapies. Homologous recombination repair (HRR) gene alterations, including alterations, can sensitize cancer cells to poly (ADP-ribose) polymerase inhibition, which may improve outcomes in treatment-naïve mCRPC when combined with androgen receptor signaling inhibition.

METHODS

MAGNITUDE (ClinicalTrials.gov identifier: NCT03748641) is a phase III, randomized, double-blinded study that evaluates niraparib and abiraterone acetate plus prednisone (niraparib + AAP) in patients with (HRR+, n = 423) or without (HRR-, n = 247) HRR-associated gene alterations, as prospectively determined by tissue/plasma-based assays. Patients were assigned 1:1 to receive niraparib + AAP or placebo + AAP. The primary end point, radiographic progression-free survival (rPFS) assessed by central review, was evaluated first in the subgroup and then in the full HRR+ cohort, with secondary end points analyzed for the full HRR+ cohort if rPFS was statistically significant. A futility analysis was preplanned in the HRR- cohort.

RESULTS

Median rPFS in the subgroup was significantly longer in the niraparib + AAP group compared with the placebo + AAP group (16.6 10.9 months; hazard ratio [HR], 0.53; 95% CI, 0.36 to 0.79; = .001). In the overall HRR+ cohort, rPFS was significantly longer in the niraparib + AAP group compared with the placebo + AAP group (16.5 13.7 months; HR, 0.73; 95% CI, 0.56 to 0.96; = .022). These findings were supported by improvement in the secondary end points of time to symptomatic progression and time to initiation of cytotoxic chemotherapy. In the HRR- cohort, futility was declared per the prespecified criteria. Treatment with niraparib + AAP was tolerable, with anemia and hypertension as the most reported grade ≥ 3 adverse events.

CONCLUSION

Combination treatment with niraparib + AAP significantly lengthened rPFS in patients with HRR+ mCRPC compared with standard-of-care AAP.

UNLABELLED

[Media: see text].

摘要

目的

转移性去势抵抗性前列腺癌（mCRPC）仍是一种致命疾病，目前的标准治疗方法仍然如此。同源重组修复（HRR）基因改变，包括改变，可使癌细胞对聚（ADP-核糖）聚合酶抑制敏感，当与雄激素受体信号抑制联合使用时，可能改善治疗初治 mCRPC 的预后。

方法

MAGNITUDE（ClinicalTrials.gov 标识符：NCT03748641）是一项 III 期、随机、双盲研究，评估尼拉帕利联合醋酸阿比特龙加泼尼松（尼拉帕利+AAP）在 HRR 阳性（n = 423）或 HRR 阴性（n = 247）患者中的疗效，HRR 相关基因改变通过组织/血浆检测方法前瞻性确定。患者按 1:1 比例接受尼拉帕利+AAP 或安慰剂+AAP 治疗。主要终点为中心评估的影像学无进展生存期（rPFS），首先在亚组中进行评估，然后在全 HRR+队列中进行评估，如果 rPFS 具有统计学意义，则对全 HRR+队列进行次要终点分析。HRR-队列中预先计划了一项无效性分析。

结果

亚组中尼拉帕利+AAP 组的中位 rPFS 明显长于安慰剂+AAP 组（16.6 10.9 个月；风险比[HR]，0.53；95%置信区间[CI]，0.36 至 0.79； =.001）。在全 HRR+队列中，尼拉帕利+AAP 组的 rPFS 明显长于安慰剂+AAP 组（16.5 13.7 个月；HR，0.73；95%CI，0.56 至 0.96； =.022）。这些发现得到了次要终点的支持，包括症状进展时间和开始细胞毒性化疗时间的改善。在 HRR-队列中，根据预设标准宣布无效。尼拉帕利+AAP 治疗耐受性良好，最常见的 3 级不良事件为贫血和高血压。