他拉唑帕利联合恩扎卢胺治疗转移性去势抵抗性前列腺癌：来自随机、安慰剂对照、III 期 TALAPRO-2 研究的安全性分析。

Talazoparib plus enzalutamide in metastatic castration-resistant prostate cancer: Safety analyses from the randomized, placebo-controlled, phase III TALAPRO-2 study.

机构信息

Peter MacCallum Cancer Centre, Melbourne, Australia.

Institut Gustave Roussy, University of Paris-Saclay, Villejuif, France.

出版信息

Eur J Cancer. 2024 Dec;213:115078. doi: 10.1016/j.ejca.2024.115078. Epub 2024 Oct 20.

DOI:10.1016/j.ejca.2024.115078

PMID:39486165

Abstract

BACKGROUND

This detailed analysis further characterizes the safety profile of talazoparib plus enzalutamide in the ongoing randomized, phase III TALAPRO-2 study in patients with metastatic castration-resistant prostate cancer (mCRPC). In both the all-comers and homologous recombination repair (HRR)-deficient populations, talazoparib plus enzalutamide significantly improved radiographic progression-free survival compared with placebo plus enzalutamide.

METHODS

The talazoparib plus enzalutamide safety populations in TALAPRO-2 included 398 patients from cohort 1 (all-comers, unselected for HRR gene alterations) and 198 patients from the combined HRR-deficient population (patients from the all-comers population with HRR gene alterations plus subsequently enrolled patients with HRR gene alterations; cohort 2). Patients received talazoparib 0.5 mg (0.35 mg, moderate renal impairment) and enzalutamide 160 mg once daily. Safety analyses evaluated common treatment-emergent adverse events (TEAE), their type, severity, timing, seriousness, and relationship to study treatment.

RESULTS

In the all-comers (n = 398) and HRR-deficient populations (n = 198), all-cause grade 3/4 (G3/4) TEAEs with talazoparib plus enzalutamide were reported in 71.9 % and 66.2 % of patients, respectively. Most common G3/4 hematologic TEAEs were anemia (46.7 % and 40.9 %, respectively), neutropenia (18.3 % and 18.7 %), and thrombocytopenia (7.3 % and 7.1 %). Median time to event was 3.3 and 3.3 months for G3/4 anemia, 2.3 and 2.3 months for G3/4 neutropenia, and 2.3 and 1.5 months for G3/4 thrombocytopenia. Maximum hemoglobin reduction occurred after 13 and 15 weeks of treatment. 18.8 % and 10.1 % of patients discontinued talazoparib. TEAEs were managed with dose interruption (62.1 % and 57.6 %), reduction (52.8 % and 52.0 %), hematologic supportive care (13.1 % and 10.6 %), and packed red blood cell transfusions (39.2 % and 35.9 %).

CONCLUSION

Talazoparib plus enzalutamide had a generally manageable safety profile in patients with mCRPC within the all-comers and the HRR-deficient populations.

GOV IDENTIFIER

NCT03395197.

摘要

背景

这项详细分析进一步描述了在转移性去势抵抗性前列腺癌（mCRPC）患者中进行的正在进行的随机、III 期 TALAPRO-2 研究中，他拉唑帕利联合恩扎卢胺的安全性概况。在所有患者和同源重组修复（HRR）缺陷人群中，与安慰剂联合恩扎卢胺相比，他拉唑帕利联合恩扎卢胺显著改善了影像学无进展生存期。

方法

TALAPRO-2 中的他拉唑帕利联合恩扎卢胺安全性人群包括来自队列 1（所有患者，未选择 HRR 基因改变）的 398 例患者和联合 HRR 缺陷人群（队列 2）中的 198 例患者。患者接受他拉唑帕利 0.5mg（中度肾功能损害时为 0.35mg）和恩扎卢胺 160mg 每日一次。安全性分析评估了常见的治疗中出现的不良事件（TEAE）、其类型、严重程度、发生时间、严重程度以及与研究治疗的关系。

结果

在所有患者（n=398）和 HRR 缺陷人群（n=198）中，他拉唑帕利联合恩扎卢胺分别有 71.9%和 66.2%的患者出现任何原因的 3/4 级（G3/4）TEAE。最常见的 G3/4 血液学 TEAE 为贫血（分别为 46.7%和 40.9%）、中性粒细胞减少症（分别为 18.3%和 18.7%）和血小板减少症（分别为 7.3%和 7.1%）。G3/4 贫血的中位时间分别为 3.3 和 3.3 个月，G3/4 中性粒细胞减少症的中位时间分别为 2.3 和 2.3 个月，G3/4 血小板减少症的中位时间分别为 2.3 和 1.5 个月。最大血红蛋白下降发生在治疗的 13 周和 15 周后。分别有 18.8%和 10.1%的患者停止使用他拉唑帕利。TEAE 通过剂量中断（62.1%和 57.6%）、剂量减少（52.8%和 52.0%）、血液学支持治疗（13.1%和 10.6%）和红细胞输注（39.2%和 35.9%）进行管理。