Pfizer Inc. (NYSE: PFE) today announced positive results from the Phase 3 TALAPRO-2 study of TALZENNA® (talazoparib), an oral poly ADP-ribose polymerase (PARP) inhibitor, in combination with XTANDI® (enzalutamide), an androgen receptor pathway inhibitor (ARPI), demonstrating a statistically significant and clinically meaningful improvement in overall survival (OS) compared to placebo plus XTANDI in patients with metastatic castration-resistant prostate cancer (mCRPC), with or without homologous recombination repair (HRR) gene mutations. The TALAPRO-2 results will be presented at the American Society of Clinical Oncology Genitourinary (ASCO GU) Cancers Symposium in San Francisco and featured in the ASCO GU official Press Program.

辉瑞公司 (NYSE: PFE) 今天宣布了 TALZENNA ® (talazoparib)（一种口服聚 ADP-核糖聚合酶 (PARP) 抑制剂）与 XTANDI ® (enzalutamide)（一种雄激素受体途径抑制剂 (ARPI)）联合使用的 3 期 TALAPRO-2 研究的积极结果，结果显示与安慰剂联合 XTANDI 相比，转移性去势抵抗性前列腺癌 (mCRPC) 患者（无论是否伴有同源重组修复 (HRR) 基因突变）的总生存率 (OS) 有统计学和临床​​意义的改善。TALAPRO-2 结果将在旧金山举行的美国临床肿瘤学会泌尿生殖系统 (ASCO GU) 癌症研讨会上公布，并在 ASCO GU 官方新闻计划中介绍。

The TALAPRO-2 study evaluated two sets of patients, unselected (cohort 1) and selected for HRR gene-mutations (cohort 2). Overall survival was a prespecified, alpha-protected key secondary endpoint. After more than four years of median follow-up (52.5 months), the median OS in cohort 1 was 45.8 months with TALZENNA in combination with XTANDI, and 37.0 months with XTANDI and placebo (Hazard Ratio [HR] of 0.80; 95% Confidence Interval [CI], 0.66-0.96; p=0.015), representing a 20% reduction in the risk of death. This represents a nearly 9-month gain in median OS versus standard of care XTANDI. Data from cohort 1 will be presented today at ASCO GU in an oral presentation (Abstract LBA18) by Dr. Neeraj Agarwal, global lead investigator for TALAPRO-2.

TALAPRO-2 研究评估了两组患者，一组未经选择（队列 1），一组因 HRR 基因突变而选择（队列 2）。总生存期是预先设定的、受 alpha 保护的关键次要终点。经过超过四年的中位随访（52.5 个月），队列 1 中位 OS 为 TALZENNA 与 XTANDI 联合治疗的 45.8 个月，XTANDI 与安慰剂联合治疗的 37.0 个月（风险比 [HR] 为 0.80；95% 置信区间 [CI]，0.66-0.96；p=0.015），代表死亡风险降低了 20%。与标准治疗 XTANDI 相比，这意味着中位 OS 增加了近 9 个月。第 1 组的数据将于今日在 ASCO GU 上以口头报告（摘要 LBA18）的形式由 TALAPRO-2 全球首席研究员 Neeraj Agarwal 博士介绍。

In Cohort 2, a statistically significant and clinically meaningful improvement in OS was observed in patients with HRR-mutated mCRPC. At a median follow-up of 44.2 months, the median OS was 45.1 months with TALZENNA in combination with XTANDI, and 31.1 months with XTANDI and placebo (HR of 0.62; 95% CI, 0.48-0.81; p=0.0005), a 38% reduction in the risk of death. This result represents a 14-month gain in median OS versus standard of care XTANDI in a patient population with a historically poor prognosis. The OS improvement in the HRR-mutated population was observed in patients in both BRCA and non-BRCA gene alterations. Dr. Karim Fizazi, Institut Gustave Roussy, University of Paris-Saclay will share data from Cohort 2 at ASCO GU today (Abstract LBA141).

在第 2 组，HRR 突变 mCRPC 患者的 OS 出现统计学显著且具有临床意义的改善。在 44.2 个月的中位随访期内，TALZENNA 与 XTANDI 联合治疗的中位 OS 为 45.1 个月，XTANDI 与安慰剂联合治疗的中位 OS 为 31.1 个月（HR 为 0.62；95% CI，0.48-0.81；p=0.0005），死亡风险降低 38%。这一结果表示，在历史预后较差的患者群体中，与标准治疗 XTANDI 相比，中位 OS 增加了 14 个月。在 BRCA 和非 BRCA 基因变异的患者中均观察到 HRR 突变人群的 OS 改善。巴黎萨克雷大学 Gustave Roussy 研究所的 Karim Fizazi 博士今天将分享 ASCO GU 第 2 组的数据（摘要 LBA141）。

“Since its approval, TALZENNA in combination with XTANDI has redefined the standard of care for those living with homologous recombination repair gene-mutated mCRPC. These latest data from TALAPRO-2 are extremely compelling, demonstrating that the combination significantly extended overall survival, in patients selected and unselected for HRR gene alterations, potentially shifting the treatment paradigm for all men living with mCRPC,” said Roger Dansey, M.D., Chief Oncology Officer, Pfizer. “Although definitive conclusions cannot be drawn across studies, these results appear to represent the longest median overall survival reported in a randomized, controlled Phase 3 trial in mCRPC. We look forward to continuing to work with global authorities to potentially update the TALZENNA label with these results.”

辉瑞公司首席肿瘤学官 Roger Dansey 医学博士表示：“自获批以来，TALZENNA 与 XTANDI 的联合用药重新定义了同源重组修复基因突变的 mCRPC 患者的治疗标准。TALAPRO-2 的最新数据非常引人注目，表明该联合用药显著延长了 HRR 基因变异患者和未变异患者的总生存期，有可能改变所有 mCRPC 患者的治疗模式。”“虽然无法从所有研究中得出明确的结论，但这些结果似乎代表了 mCRPC 随机对照 3 期试验中报告的最长中位总生存期。我们期待继续与全球监管机构合作，利用这些结果更新 TALZENNA 标签。”

“TALAPRO-2 is the first study demonstrating a significant and clinically meaningful survival benefit using a combination of PARP and androgen receptor inhibitors in mCRPC,” said Neeraj Agarwal, M.D., FASCO, Professor and Presidential Endowed Chair of Cancer Research at Huntsman Cancer Institute, University of Utah, and global lead investigator for TALAPRO-2. “Survival rates in metastatic castration-resistant prostate cancer are poor due to the advanced and aggressive stage of the disease. Today’s results demonstrate the potential for TALZENNA in combination with XTANDI to be a practice-changing treatment to help improve patient survival in mCRPC.”

犹他大学亨茨曼癌症研究所教授兼癌症研究主席、TALAPRO-2 全球首席研究员 Neeraj Agarwal 医学博士、FASCO 表示：“TALAPRO-2 是第一项证明 PARP 和雄激素受体抑制剂联合治疗 mCRPC 具有显著且具有临床意义的生存益处的研究。转移性去势抵抗性前列腺癌的生存率较低，因为该病处于晚期且侵袭性阶段。今天的结果表明，TALZENNA 与 XTANDI 联合使用有可能成为一种改变实践的治疗方法，有助于提高 mCRPC 患者的生存率。”

At the time of the final analysis, updated radiographic progression free survival (rPFS) and other secondary efficacy endpoints demonstrated maintained clinical benefit in both cohorts and were consistent with the primary analyses previously reported and published in The Lancet and Nature Medicine .

在最终分析时，更新的放射学无进展生存期（rPFS）和其他次要疗效终点均表明两个队列均保持了临床益处，并且与 之前在《柳叶刀》 和 《自然医学》上报告 和发表的 主要分析一致 。

In addition to the FDA, these data have been shared with the European Medicines Agency (EMA) and other global health authorities to support potential updates of the approved labels for TALZENNA.

除了 FDA 之外，这些数据还与欧洲药品管理局 (EMA) 和其他全球卫生当局共享，以支持 TALZENNA 批准标签的潜在更新。

The safety profile of TALZENNA plus XTANDI was generally consistent with the known safety profile of each medicine. The most common all-cause adverse events in the TALZENNA group (≥30% of patients) were anemia, neutropenia, and fatigue, and the most common (≥10% of patients) grade 3–4 adverse events were anemia (49%) and neutropenia (19.3%). Adverse events were generally manageable with dose modification and supportive care.

TALZENNA 加 XTANDI 的安全性与每种药物已知的安全性基本一致。TALZENNA 组最常见的全因不良事件（≥30% 的患者）是贫血、中性粒细胞减少和疲劳，最常见的（≥10% 的患者）3-4 级不良事件是贫血（49%）和中性粒细胞减少（19.3%）。不良事件通常可以通过调整剂量和支持治疗来控制。