| 徐一鹏,王 鹤,谢 丽.他拉唑帕尼联合恩扎鲁胺一线治疗转移性去势抵抗性前列腺癌患者（TALAPRO-2）：一项随机、安慰剂对照、Ⅲ期临床试验结果解读[J].肿瘤学杂志,2023,29(8):720-727. |
| 他拉唑帕尼联合恩扎鲁胺一线治疗转移性去势抵抗性前列腺癌患者（TALAPRO-2）：一项随机、安慰剂对照、Ⅲ期临床试验结果解读 |
| Talazoparib plus Enzalutamide in Men with First-Line Metastatic Castration-Resistant Prostate Cancer (TALAPRO-2)： Interpretation of a Randomised， Placebo-Controlled， Phase Ⅲ Trial |
| 投稿时间：2023-08-15 |
| DOI：10.11735/j.issn.1671-170X.2023.08.B013 |
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| 中文关键词: 转移性去势抵抗性前列腺癌 他拉唑帕尼 恩扎鲁胺 临床试验 |
| 英文关键词:metastatic castration-resistant prostate cancer Talazoparib Enzalutamide clinical trial |
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| 中文摘要: |
| 摘 要：TALAPRO-2是一项国际多中心、随机、双盲、安慰剂对照的Ⅲ期研究，在北美、欧洲、以色列、南美、南非和亚太地区的26个国家（地区）的223家医院、癌症中心和医疗中心开展。研究对比了他拉唑帕尼加恩扎鲁胺方案（治疗组）与安慰剂加恩扎鲁胺方案（对照组）一线治疗转移性去势抵抗型前列腺癌（metastatic castration-resistant prostate cancer，mCRPC）患者的疗效、安全性和患者报告结局（patient-reported outcome，PRO）。并结合患者的HRR基因突变状态等因素进行了亚组分析。2019年1月7日至2020年9月17日期间，研究一共纳入了805例患者。2023年最新公布的数据中，TALAPRO-2研究公布了主要终点［经盲法独立中心审查评估的影像学无进展生存期（radiographic progression free survival，rPFS)］全人群获益的结果：治疗组患者未达到中位rPFS（95%CI：27.5个月～未达到），对照组的rPFS为21.9个月（95%CI：16.6～25.1）（HR=0.63，95%CI：0.51～0.78，P＜0.001）。在预先设定的亚组中也得到了一致的获益。但该研究目前的总生存期数据尚未成熟（成熟度为31%）。在不良反应方面，治疗组常见的治疗后不良事件是贫血、中性粒细胞减少和疲乏，其中，常见的3～4级不良反应是贫血（46%），在剂量减少后得以改善。治疗组患者没有发生治疗相关的死亡，但对照剂组有2例患者（<1%）出现了治疗相关性的死亡。对于mCRPC患者，相比较于恩扎鲁胺单药的标准治疗方案，他拉唑帕尼联合恩扎鲁胺治疗组的rPFS出现了具有临床意义和统计学差异的改善。最终总生存期数据和额外的长期安全性随访将进一步阐明联合治疗在伴有和不伴有肿瘤HRR基因改变的患者中的临床获益。 |
| 英文摘要: |
| Abstract： TALAPRO-2 constitutes a phase Ⅲ study of international scope， spanning 26 countries across North America， Europe， Israel， South America， South Africa， and the Asia-Pacific region. This multicenter， randomized， double-blind， placebo-controlled trial was conducted in 223 medical facilities， including hospitals and cancer centers. The investigation focused on assessing the efficacy， safety， and patient-reported outcome (PRO) of the treatment regimen involving talazoparib and enzalutamide (treatment arm) in comparison to the placebo plus enzalutamide regimen (control arm) for front-line therapy in patients with metastatic castration-resistant prostate cancer (mCRPC). Notably， the study incorporated subgroup analyses to consider variables such as patients’ HRR gene alteration status. Between January 7， 2019， and September 17， 2020， the study enrolled a total of 805 patients. The most recent data， published in 2023， unveiled findings regarding the primary endpoint ［radiographic progression free survival (rPFS) assessed through a blinded independent central review］ that demonstrated benefits across the entire patient cohort. Specifically， patients in the treatment group did not achieve the median rPFS (95%CI： 27.5 months-not attained)， while the control group displayed a median rPFS of 21.9 months (95%CI： 16.6～25.1) (HR=0.63， 95%CI：0.51～0.78， P＜0.001). Consistently favorable outcomes were also evident within pre-defined subgroups. However， the study’s maturity level concerning overall survival data currently stands at 31%. In terms of adverse events， the treatment group commonly experienced post-treatment adverse effects such as anemia， neutropenia， and fatigue. Among these， the most prevalent grade 3～4 adverse reaction was anemia (46%)， which showed improvement with dose reduction. While no treatment-related deaths occurred within the treatment group， two patients (<1%) in the control group succumbed to treatment-related causes. In the context of mCRPC patients， the combination therapy of talazoparib and enzalutamide demonstrated both clinical significance and statistical divergence in rPFS when compared to the standard enzalutamide monotherapy. The eventual provision of comprehensive overall survival data and extended safety assessments will provide further insights into the clinical advantages associated with combination therapy for patients with and without tumor HRR gene alterations. |
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