预约演示
更新于：2025-07-19
Bicalutamide
比卡鲁胺
更新于：2025-07-19
概要
基本信息
原研机构 |
非在研机构- |
最高研发阶段批准上市 |
首次获批日期 英国 (1995-02-23), |
最高研发阶段(中国)批准上市 |
特殊审评加速批准 (美国) |
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结构/序列
分子式C18H14F4N2O4S |
InChIKeyLKJPYSCBVHEWIU-UHFFFAOYSA-N |
CAS号90357-06-5 |
关联
198
项与 比卡鲁胺 相关的临床试验CTRI/2025/04/085182
Comparing the efficacy and safety of 5% topical minoxidil combined with oral bicalutamide versus 5% topical minoxidil in the treatment of female pattern hair loss: A randomized controlled trial
开始日期2026-04-06 |
申办/合作机构- |
CTR20251531
中国健康受试者餐后口服比卡鲁胺片单中心、开放、随机、单剂量、两周期、两序列、自身交叉设计的生物等效性试验
主要目的：研究餐后状态下单次口服受试制剂（T）比卡鲁胺片（规格：50mg，浙江皓格药业有限公司生产，杭州和泽坤元药业有限公司提供）与参比制剂（R）比卡鲁胺片（规格：50mg，商品名：康士得®，持证商：AstraZeneca UK Limited）在受试者体内的吸收速度和吸收程度的差异。
次要目的：评价受试者餐后单次口服比卡鲁胺片受试制剂（T）和参比制剂（R）后的安全性。
开始日期2025-05-06 |
申办/合作机构 |
CTR20251530
中国健康受试者空腹口服比卡鲁胺片单中心、开放、随机、单剂量、两周期、两序列、自身交叉设计的生物等效性试验
主要目的：研究空腹状态下单次口服受试制剂（T）比卡鲁胺片（规格：50mg，浙江皓格药业有限公司生产，杭州和泽坤元药业有限公司提供）与参比制剂（R）比卡鲁胺片（规格：50mg，商品名：康士得®，持证商：AstraZeneca UK Limited）在受试者体内的吸收速度和吸收程度的差异。
次要目的：评价受试者空腹单次口服比卡鲁胺片受试制剂（T）和参比制剂（R）后的安全性。
开始日期2025-05-06 |
申办/合作机构 |
100 项与 比卡鲁胺 相关的临床结果
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100 项与 比卡鲁胺 相关的转化医学
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100 项与 比卡鲁胺 相关的专利（医药）
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3,167
项与 比卡鲁胺 相关的文献（医药）2025-12-31·CANCER BIOLOGY & THERAPY
Assessing the potential for in vivo modulation of
FTH1 gene
expression with small peptides to restore and enhance androgen receptor pathway inhibition in prostate cancer
Article
作者: Nicol, McKayla ; Kumar, Sateesh ; Currie, Crawford ; Framroze, Bomi ; Bjerknes, Christian
Increased levels of intratumoral free iron drive more aggressive behavior with the development of treatment resistance and spread in a range of cancers including prostate cancer (PCa). This phenotype is associated with an increase in TFRC expression and a decrease in FTH1, a profile supporting increased iron acquisition. In this study we investigated the anti-oncogenic effects of two small peptides (FT-002 and FT-005) that upregulate FTH1 expression and downregulate TFRC expression when combined with standard androgen receptor pathway inhibitors (ARPIs) in xenograft models of PCa in male athymic nude mice. The PC3 cell line was used to establish xenografts representing highly aggressive, androgen-resistant PCa and the LNCaP cell line as a model of androgen-sensitive PCa. Both peptides enhanced the anti-tumor efficacy of ARPI therapy. Efficacy was more marked with the combination of the second-generation APRI enzalutamide than the first-generation agent bicalutamide, a result consistent with known resistance mechanisms to different ARPI therapy. Further, the FT-peptide/enzalutamide combination drove tumor regression whereas enzalutamide monotherapy only slowed growth, even in the hormone-sensitive xenograft. The FT-002a-enzalutamide combination was more effective than FT-005 in reducing tumor mass and volume and modulating FTH1 and TFRC expression. The reversal by the peptides of this oncogenic expression pattern points to a reduction in the tumor free iron via increased iron storage in ferritin and a reduction in iron influx via the transferrin receptor. Peptide-mediated modulation of tumor iron metabolism may therefore offer a novel means to enhance ARPI efficacy and delay resistance in advanced prostate cancer.
2025-09-01·ENVIRONMENTAL POLLUTION
Validation of a large volume-solid phase extraction methodology for biotoxicity assessment of pharmaceuticals in aquatic organisms
Article
作者: Gómez-Canela, Cristian ; Moragrega-Knol, Emma ; Barata, Carlos ; Romero-Alfano, Irene
The growing scarcity of freshwater has intensified the need for alternative water sources, which often require advanced treatments to eliminate contaminants. Among emerging pollutants, pharmaceuticals have become a significant concern due to their persistence and potential impact, making their detection essential. However, analysing these contaminants is challenging due to the extremely low concentrations at which they are present. For chemical analysis, minimal or no sample enrichment is often necessary, while bioanalysis typically requires larger sample volumes and an enrichment factor to conduct comprehensive bioassays across various endpoints. Consequently, sample preconcentration techniques for large water volumes are necessary to improve the sensitivity of subsequent toxicological experiments. In this study, a novel large volume solid-phase extraction (LV-SPE) procedure was validated and evaluated for monitoring multiple pharmaceutical compounds in water samples, while maintaining the traditional solid-phase extraction (SPE) methodology using cartridges. This method proved effective extraction and preconcentration of significant amounts of water, with recoveries between 19 % and 109 % in spiked wastewaters (except for fluvoxamine, remdesivir, tamoxifen and tetracycline, with recoveries <10 %). Furthermore, the optimization of this approach covers an expansive chemical space, enabling the capture of a diverse range of pharmaceutical compounds and enhancing the validity of toxicological studies. Bioassays conducted with Daphnia magna juveniles and Danio rerio embryos validated the method's applicability regarding optimized exposure conditions, the absence of adverse effects from SPE blanks or solvent controls and sensitivity in detecting effects across field samples. Overall, the LV-SPE approach enhances sensitivity and reliability for evaluating pharmaceutical mixtures' risks under realistic conditions.
2025-08-01·JOURNAL OF HAZARDOUS MATERIALS
A framework to assess pharmaceutical accumulation in crops: from wastewater irrigation to consumption
Article
作者: Trapp, Stefan ; Garduño-Jiménez, Andrea ; Nightingale, John ; Carter, Laura
The reuse of treated wastewater for irrigation can inadvertently introduce a suite of emerging contaminants such as pharmaceuticals into agri-ecosystems. However, current monitoring efforts to characterise exposure usually focus on a limited range of analytes. A modelling framework was developed that employs a sequence of pre-developed models to predict accumulative potential in a model crop, Zea mays (corn), using chemical structure and excretion rate as the only model inputs. Z. mays was selected as the model crop as it is a major food source, stands as one of the highest cultivated crops globally, and is characterised as having a medium uptake potential. The framework was used to predict uptake in Z. mays in three regions characteristic of high wastewater reuse (Australia, the US and the Middle East). Despite regional and plant specific differences, 72.7 % of the calculated concentrations were within a factor of ten of those reported in the literature. Topiramate, furosemide, and gemfibrozil were observed to accumulate to the greatest extent in Z. mays, predicted concentrations ranged between 50.27 and 418.01 ng/g (dw) for the top 10. Acids predominantly accumulated in leaves and fruit whereas a higher proportion of bases were predicted to accumulate in the roots. To the best of our knowledge 56.7 % of the 30 highest-ranked pharmaceuticals have not been previously documented in existing literature or monitoring campaigns. This presented framework demonstrates a method to assess risk posed by pharmaceutical compounds with limited experimental data.
67
项与 比卡鲁胺 相关的新闻（医药）2025-07-09
·药学进展
“点击蓝字 关注我们焦宇中国药科大学副教授，2011 年毕业于中国科学院上海药物所，获药物化学博士学位。2016 年 9 月至 2017 年 10 月作为访问学者在美国明尼苏达大学药学院进行科研工作。现主要研究方向为：1）靶向雄激素受体的药物化学研究；2）小分子神经系统药物的发现与开发。发表 SCI 论文 21 篇（J Med Chem,Euro J Med Chem, Anal Chem 等 Q1 区期刊），授权发明专利 5 项。去势抵抗性前列腺癌患者对雄激素受体拮抗剂耐药机制的研究进展 PPS 樊亚雯，彭胜宽，裴升，焦宇*（中国药科大学理学院, 江苏 南京 211198）[ 摘要 ] 前列腺癌是困扰全球男性的重大癌症疾病之一，近年来发病率不断升高。雄激素受体（androgen receptor, AR）信号通路一直是前列腺癌治疗的关键通路，据此采取的包括雄激素剥夺治疗（androgen-depri-vation therapy, ADT）、AR 拮抗剂等激素治疗方法仅对早期非转移性疾病明显有效，绝大部分患者晚期进展为去势抵抗性前列腺癌（castration-resistant prostate cancer, CRPC）。近年来，针对 CRPC 患者对 AR 拮抗剂耐药机制的研究取得了显著进展。通过对 AR 信号通路异常、AR 基因突变、AR 共调节因子改变等机制在CRPC 患者对 AR 拮抗剂耐药中的作用进行综述，并对目前 PCa 治疗中针对 AR 拮抗剂的相关耐药机制进行研究，旨在为相关新型拮抗剂的研发及临床治疗方案的设计提供参考。前列腺癌是影响男性健康的恶性肿瘤之一。随着人口老龄化和生活方式的改变，前列腺癌的发病率不断升高。据报道，2023 年美国调查数据中，全球男性患病率较高的排名前 10 的肿瘤依次是前列腺癌、肺癌、结直肠癌、膀胱癌、黑色素瘤、肾癌、非霍奇金淋巴瘤、口腔和咽喉癌、白血病、胰腺癌 [1]，其中发病率最高的前列腺癌患者约占 29%。而中国前列腺癌的发病率和死亡率也在逐年增加 [2]。尽管前列腺癌前期有可用的治疗方案，但最终仍然难以治愈。由于晚期往往会发展为去势抵抗性前列腺癌（castration-resistant prostate cancer，CRPC），因此，一直在寻找和确定更好的治疗方案 [3]。自 20 世 纪 40 年代初，Huggins 和 Hodges 发现雄激素可促进前列腺肿瘤生长以来，雄激素疗法一直是前列腺癌最有效和最广泛使用的治疗方法。积极监测、局部治疗和雄激素剥夺治疗（androgen depri-vation therapy，ADT）对早期非转移性疾病非常有效，但约 10% ~ 50% 的病例最终会在 3 年内对该方法产生耐药性，称为“去势抵抗性”[4]。第 1 代雄激素受体（androgen receptor，AR） 拮抗剂包括氟他胺（1）、尼鲁米特（2）和比卡鲁胺（3）（见图 1），分别于 1989 年、1995 年1996 年获得美国食品药品监督管理局（Food and Drug Administration，FDA）批准。尽管患者在疾病早期阶段接受第 1 代 AR 拮抗剂治疗后，症状表现出一定程度的缓解，但最终会获得耐药性并发展为致死性 CRPC，在临床 CRPC 患者和临床前前列腺癌细胞模型中，经常观察到 AR 过表达等耐药突变 [5]。第 2 代 AR 拮抗剂具有更高的 AR 结合亲和力和特异性，以靶向 CRPC 患者中的异常 AR 信号传导通路，如恩杂鲁胺（MDV3100，4）[6]、阿帕鲁胺（ARN-509，5）[7]、达罗鲁胺（ODM-201，6）[8]，其结构如图 2 所示。但第 2 代药物的临床治疗过程仍然不可避免地出现获得性耐药 [9]，限制了治疗方案的稳定性，因此前列腺癌的耐药性 AR 拮抗剂有待进一步研发。一项对转移性去势抵抗性前列腺癌（metastatic castration-resistant prostate cancer，mCRPC）患者的转录组测序结果表明，71.3% 的病例存在 AR 通路相关基因突变 [10]。此外，磷脂酰肌醇 3- 激酶（phosphoinositide 3-kinase，PI3K）/ 蛋白激酶 B（protein kinase B，PKB）/ 第 10 号染色体缺失的磷酸酶及张力蛋白同源物 (phosphatase and tensin homolog，PTEN)信号通路、核因子κB亚基2（nuclear factor kappa B subunit 2，NF-κB2）信号通路、无翅型 / 整合型蛋白（wingless/integrated，Wnt）信号通路等其他信号通路也与 CRPC 的耐药特性有关 [11] 。本文旨在对前列腺癌治疗中 AR 通路的耐药机制研究进行综述，为相关新型拮抗剂的设计及临床治疗方案提供参考。1雄激素受体的结构和信号通路AR 基因位于 X 染色体的长臂上，包含 8 个外显子，内含子长度不等（0.7~2.6 kb），最终编码出的蛋白质含 919 个氨基酸。AR 包含 3 个主要功能域：N 末 端 结 构 域（N-terminal domain，NTD），DNA 结合结构域（DNA binding domain，DBD）和配体结合结构域（ligand binding domain，LBD）[12]。NTD 位于 AR 的 N 端，占 AR 一半以上，保守性低，与 AR 的反式激活功能相关 [13]。NTD 包含激活功能 1（activation function 1，AF1）区，该处含两个转录激活单位：Tau-1（氨基酸 100 ~ 370）和 Tau-5（氨基酸 360 ~ 485），介导 NTD 和 LBD 之间直接的配体依赖性结构域间相互作用 [14]，有助于稳定AR 二聚体复合物并减缓配体解离速率 [15]。DBD 富含半胱氨酸，具有保守的氨基酸序列，其包含由两个锌指结构组成的核心，每个锌指结构由 4 个半胱氨酸残基组成 [16]。其中，N 端锌指结构的 α 螺旋与DNA 螺旋大沟中作为反应元件的核苷酸相互作用。另一锌指结构不与 DNA 相互作用，但其中保守氨基酸可以介导 AR 受体单体之间的二聚化，并稳定DNA 和 AR 结合的复合物。DBD 和 LBD 之间的区域为铰链区，序列保守性较差，其与 DBD 的连接处序列具有核定位功能 [17-18]。LBD 晶体结构中有由 3 个 α 螺旋形成的配体结合口袋（ligand-binding pocket，LBP），该区域需要配体结合才能激活。当 LBD 被剪接形成剪接异构体时，该蛋白可能会发生功能突变，不再需要配体结合来激活，导致蛋白表达失调。AR 属于核受体超家族中的类固醇受体 [19]，是一种配体依赖的转录因子，控制特定基因表达。生理条件下，睾酮经分泌后以游离形式进入细胞内，被转化为 5α- 二氢睾酮（dihydrotestosterone，DHT），以高亲和力与 AR 结合，引起 AR 的构象变化，使 AR 与热休克蛋白（heat shock protein，HSP）分离，随后募集共调节因子，进行二聚化后移位至细胞核中。在细胞核中，AR 二聚体与目标基因启动子区域的雄激素反应元件（androgen response element，ARE）结合，如前列腺特异性抗原（prostate specific antigen，PSA）和跨膜蛋白酶等，随后招募各种共调节蛋白以促进下游基因的转录 [19]。在雄激素非依赖性 AR 途径中，AR 和 AR 突变体可在没有雄激素启动的情况下二聚化 [20]。该情况下，AR 可以在没有雄激素情况下被表皮生长因子、胰岛素样生长因子等激活 [21]，从而导致核移位和基因转录增加。AR 不仅与正常前列腺的发育和功能相关，而且对前列腺癌细胞的生长和维持也起重要作用，在正常前列腺中，AR 的主要作用是促进上皮细胞的分化，并调节编码前列腺功能所必需的蛋白质（如前列腺特异性抗原）的基因转录；在前列腺癌患者中，雄激素代谢产物与雄激素受体结合，调节细胞周期且促进前列腺癌相关基因表达，导致前列腺癌患者的肿瘤生存、生长 [22]。2雄激素受体通路耐药机制与治疗策略AR 通路相关基因突变是产生 CRPC 耐药的主要原因 [13]。尽管临床治疗引起雄激素的合成减少，但各种 AR 基因组的突变导致 AR 信号通路激活的可能性增加，包括AR扩增、点突变和剪接突变体等，这些耐药突变使得针对前列腺癌的 AR 靶向治疗遇到困难。2.1 雄激素受体扩增在早期复发性前列腺癌患者中，经常出现 AR扩增导致的获得性耐药，致使前列腺癌细胞在低雄激素水平下持续增殖 [23]。AR 扩增是在 CRPC 组织样本中观察到的最常见遗传改变，发生在高达 50%的前列腺癌患者体内 [24]。研究表明，在产生恩杂鲁胺或者阿比特龙耐药性过程中，AR 基因扩增或过表达起着重要的作用。对恩杂鲁胺治疗后患者血浆样本中细胞游离 DNA（cell-free DNA，cf-DNA）的分析显示，AR 拷贝数增加的频率高于接受阿比特龙治疗的患者样本。与未出现 AR 扩增的患者相比，AR 扩增患者早期疾病进展的风险增加 [25]。由于 AR拮抗剂抑制前列腺上皮细胞中的 AR 转录，作为一种负反馈调节机制，AR 扩增可能是一种代偿性的耐药机制。当药物 AR 拮抗作用较强，癌细胞则通过代偿性地增加 AR 表达来减弱治疗效果。全基因组测序结果表明，AR 扩增不仅是 AR 基因的扩增，而且通常包含其远端相关增强子的扩增 [26]。该增强子位于 AR 基因上游约 650 kb 的位置，常在 CRPC患者体内激活。已上市恩杂鲁胺为代表的具有更高AR 拮抗活性的第 2 代 AR 拮抗剂很好地改善了这一临床问题 [9]。2.2 雄激素受体点突变早期前列腺癌患者中，AR 基因突变较为罕见，但晚期雄激素非依赖性前列腺癌患者体内，AR 点突变频率显著增加。20% 的晚期 CRPC 患者体内发现 AR 突变，最常见的是 AR 的 LBD 区 [27]，包括氨基酸残基 F877L、H875Y、T878A、L702H 等， 这些突变几乎都是由于体细胞突变造成的单碱基替换而 LBD 区常作为第 1 代和第 2 代 AR 拮抗剂的作用靶点。AR 点突变常分为两类，一种是将 AR 拮抗剂转化为激动剂（例如 F877L，W742L/C）的突变；另一种是导致配体特异性扩大，使 AR 可以与其他内源性类固醇结合的突变。T878A 是 CRPC 中最常见的点突变之一。1994年，Gaddipati 等 [28] 对 mCRPC 患者的前列腺组织标本进行分析，发现部分患者存在 T878A 突变。体外实验表明，存在 T878A 的癌细胞表现出雄激素非依赖性 AR 转录激活性质，增加了 AR 对雌激素、孕激素等的亲和力 [29]。2021 年研究发现，T878A 突变还可使 AR 被糖皮质激素（如地塞米松）等激活，导致患者产生耐药性 [30]。突变后 AR 配体结合口袋处丙氨酸残基取代苏氨酸残基，丙氨酸是一种体积小于苏氨酸的氨基酸，因此，显著增加配体结合口袋的大小，使许多其他配体如雌二醇能够与 AR 结合，从而激活 AR 信号通路 [29]。2003 年的一项研究表明，将 LNCaP 细胞在体外暴露于比卡鲁胺6~13周内，最初生长会受到抑制，但后期将会通过 W742C 或 W742L 突变，使比卡鲁胺变为 AR 激动剂 [31]。2022 年研究发现，W742C突变可能通过影响 AR 的特定功能区，而非单纯扩大结合口袋，导致癌细胞发生耐药 [32]。W742L 突变可使比卡鲁胺转变为 AR 激动剂，但第 2 代抗雄药物（如恩杂鲁胺）仍能有效抑制该突变。长期使用恩杂鲁胺治疗的前列腺癌患者的癌细胞中可能发生 F877L 突变。这种突变可能改变恩杂鲁胺与 AR 结合的方式，从而使其对 AR 的作用由拮抗转变为激动。一项体外实验研究中，恩杂鲁胺在癌细胞同时具有 T878A 和 F877L 突变的情况下比单独存在 F877L 突变时表现出更强的激动效应 [33]。相反，达罗鲁胺在体外对 F877L 突变以及含其他AR 点突变的情况下显示出较强拮抗活性 [34]。此外，F877L 突变仍保留对比卡鲁胺的敏感性，因此不同结构 AR 拮抗剂的联合用药为临床治疗恩杂鲁胺耐药的前列腺癌患者提供了一种新的治疗策略。此外，H875Y 突变可使雌激素和黄体酮能够激活 AR 通路 [35]。L702H 突变可使糖皮质激素与 AR结合，常与阿比特龙耐药、强的松激活 AR 有关 [36]。2.3 雄激素受体剪接突变体AR 的选择性剪接是另一种与 CRPC 进展有关的耐药机制，18 个 AR 剪接变异体的转录结构已经完全确定，AR-V7 作为唯一已知编码的临床样本中可检测到的 AR 选择性剪接突变体，已被证实其与苯扎鲁胺和阿比特龙的耐药性存在临床关联 [37]。该剪接突变体编码 1 个截断的 AR 蛋白，此蛋白缺乏 C-末端 LBD 区，保留反式激活 NTD 区，这种构象变化使得该蛋白无法有效结合配体，但其作为转录因子具有转录活性，能够促进靶基因的激活。此外，有研究表明，AR-V7 具有不同于野生型 AR 核位移途径和较高的核位移效率。研究表明，AR-V7 对紫杉醇（7）等紫杉烷类广谱抗癌药暂时没有明显耐药性，因此可以考虑联合用药。此外，HSP 家族也与 AR 信号通路相关。HSP 27 是一种保证 AR 稳定性的细胞保护性伴侣蛋白，一项通过利用化学合成的 α-甲基酰基辅酶 A 消旋酶小干扰 RNA（alpha-methylacyl-CoA racemase small interfering RNA，AMACR siRNA）和多西他赛（8）进行的体外研究表明多西他赛和AMARC 抑制剂的双重治疗可能通过下调 HSP 27 来降低 AR-V7 的表达 [38]。HSP 90 是一种依赖三磷酸腺苷（adenosine triphosphate，ATP）的分子伴侣，与 HSP 70 及共伴侣形成动态伴侣复合物，调节包括 AR 在内的 200 多种蛋白的折叠和稳定性。一项研究发现天然抗疟药物布鲁生坦（9）可通过破坏HSP 90 与全长 AR 或 AR-V7 的相互作用，从而达到阻断 AR 信号通路的效果 [39]。甜橙黄酮（10）是一种多甲氧基类黄酮，可在体外诱导 AR-V7 的蛋白酶体降解，增强 AR-V7 阳性细胞对恩杂鲁胺的敏感性。2.4 共调节因子AR 对下游基因的转录激活功能由 150 多个共同调节因子控制，这些因子具有多种作用，包括RNA 剪接、转录因子的招募或通过磷酸化、甲基化或泛素化来调节转录复合体中的其他蛋白质。可分为共激活因子（co-activator）和共抑制因子（co-repressor）。共激活因子 FKBP51 是一种 HSP 90 辅伴侣，已被证明在具有去势抗药性小鼠中会过表达，从而促使 AR 相关超级伴侣复合体的形成，刺激 AR 与雄激素结合。有研究表明，AR-V7 高表达的患者体内检测到 FKBP51 水平升高，通过使用特定的抑制剂来结合 FKBP51 或 FKBP52（另一种 AR 共激活因子），可减少 AR 二聚体的形成 [40]。类固醇受体辅活化子（steroid receptor coactivator，SRC）以激素依赖的方式增强 AR 诱导转录信号。SCR 家族包含 3 个与前列腺癌进展相关的成员，SRC1，SRC2 和 SRC3，其中，SRC1 的磷酸化会导致AR 信号通路的激活 [41]。通过破坏 SRC1/2 和 AR 之间的相互作用，可以抑制 CRPC 癌细胞的 AR 活性 [42]。此外，Galectin-3 已被证明可以增强 AR 转录活性，导致某些 AR 下游基因的过表达，如 KLK3 和TMPRSS2。这表明 Galectin-3 在 CRPC 中可作为潜在靶点 [43]。2.5 转录后调控AR 的转录后调控是指通过乙酰化、磷酸化、甲基化、小泛素样修饰蛋白（small ubiquitin-like modifier，SUMO）化等维持细胞的生长和存活。雄激素受体降解蛋白 1（androgen receptor degradation protein 1，ARD1）是一种乙酰基转移酶，与 AR 和HSP 90 形成复合体，导致 AR 乙酰化、核移位和靶基因表达从而导致前列腺癌发生。体外和体内模型已经证明敲除 ARD1 基因可抑制 AR 的核移位 [44]，表明该基因可作为 AR 耐药治疗的新靶点。AR 丝氨酸 81（S81）处的磷酸化与 AR 重新激活有关，该磷酸化由细胞周期依赖性激酶 1（cyclin-dependent kinase 1，CDK1）和 CDK9 调控，暗示了 CDK 抑制剂在治疗CRPC 过程中的潜在作用。SUMO 化是指一种类似泛素的蛋白与靶蛋白共价结合的过程，通常可抑制 AR转录活性。SUMO 化和去 SUMO 之间的不平衡可导致肿瘤进展。此外，临床研究显示，AR 相关基因高甲基化的患者在 ADT 治疗后的预后情况更差。3结语与展望AR 信号通路在前列腺癌的各个阶段都有着重要作用，最近的研究结果表明，在高达 70% 的肿瘤表现出不同 AR 突变的患者中，AR 信号持续起着关键作用。目前已知的 AR 拮抗剂主要作用于其 LBD区，且该区域常作为耐药突变位点，导致前列腺癌患者的获得性耐药。当患者达到去势抵抗阶段，新出现的第 2 代抗雄激素药物如醋酸阿比特龙、阿帕鲁胺、恩杂鲁胺或达罗鲁胺虽能一定程度上抑制病情进展，但对包括 AR 的选择性剪接突变体、基因点突变等在内的复合型 AR 耐药突变仍然没有有效的治疗效果，使得目前 AR 拮抗剂治疗前列腺癌遭遇瓶颈。因此，目前临床上基于解决 CRPC 的关键问题是灵活选择不同治疗方案或多种治疗策略联合使用，以及新的克服 AR 耐药突变的药物发现。本研究简述了与 AR 信号通路相关的耐药突变机制研究，为新型 AR 拮抗剂的研发及创新性临床治疗方案的选择提供参考，以克服前列腺癌涉及的原发性或获得性耐药机制，有助于提升医师的临床决策强度。参考文献： [1] Siegel R L, Miller K D, Wagle N S, et al. 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FKBP51 and FKBP52 regulate androgen receptor dimerization and proliferation in prostate cancer cells[J]. Mol Oncol, 2022, 16(4): 940-956.[41] Xu J M, Wu R C, O'Malley B W. Normal and cancer-related functions of the p160 steroid receptor co-activator (SRC) family[J]. Nat Rev Cancer, 2009, 9(9): 615-630.[42] Fancher A T, Hua Y, Close D A, et al. Characterization of allosteric modulators that disrupt androgen receptor co-activator protein-protein interactions to alter transactivation-drug leads for metastatic castration resistant prostate cancer[J]. SLAS Discov, 2023, 28(7): 325-343.[43] Dondoo T O, Fukumori T, Daizumoto K, et al. Galectin-3 is implicated in tumor progression and resistance to anti-androgen drug through regulation of androgen receptor signaling in prostate cancer[J]. Anticancer Res, 2017, 37(1): 125-134.[44] Kuhns K J, Zhang G Y, Wang Z H, et al. ARD1/NAA10 acetylation in prostate cancer[J]. Exp Mol Med, 2018, 50(7): 1-8.美编排版：史鑫宇感谢您阅读《药学进展》微信平台原创好文，也欢迎各位读者转载、引用。本文选自《药学进展》2025年第 5 期。《药学进展》杂志由教育部主管、中国药科大学主办，中国科技核心期刊（中国科技论文统计源期刊）。刊物以反映药学科研领域的新方法、新成果、新进展、新趋势为宗旨，以综述、评述、行业发展报告为特色，以药学学科进展、技术进展、新药研发各环节技术信息为重点，是一本专注于医药科技前沿与产业动态的专业媒体。《药学进展》注重内容策划、加强组稿约稿、深度挖掘、分析药学信息资源、在药学学科进展、科研思路方法、靶点机制探讨、新药研发报告、临床用药分析、国际医药前沿等方面初具特色；特别是医药信息内容以科学前沿与国家战略需求相合，更加突出前瞻性、权威性、时效性、新颖性、系统性、实战性。根据最新统计数据，刊物篇均下载率连续三年蝉联我国医药期刊榜首，复合影响因子1.216，具有较高的影响力。《药学进展》编委会由国家重大专项化学药总师陈凯先院士担任主编，编委由新药研发技术链政府监管部门、高校科研院所、制药企业、临床医院、CRO、金融资本及知识产权相关机构近两百位极具影响力的专家组成。联系《药学进展》↓↓↓编辑部官网：pps.cpu.edu.cn；邮箱：yxjz@163.com；电话：025-83271227。欢迎投稿、订阅！往期推荐聚焦“兴药为民·2023生物医药创新融合发展大会”“兴药为民·2023生物医药创新融合发展大会”盛大启幕！院士专家齐聚杭城，绘就生物医药前沿赛道新蓝图“兴药强刊”青年学者论坛暨《药学进展》第二届青年编委会议成功召开“兴药为民·2023生物医药创新融合发展大会”路演专场圆满收官！校企合作新旅程已启航我知道你在看哟
放射疗法
2025-05-22
Five-year follow-up data from the Phase 3 ARCHES trial shows XTANDI (enzalutamide) plus androgen deprivation therapy (ADT) reduces risk of death by 30%
After a median follow-up of 61.4 months, treatment with XTANDI (enzalutamide) plus ADT was associated with a 66% probability of survival at five years compared to 53% probability of survival with placebo plus ADT
XTANDI (enzalutamide) is the first and only androgen receptor inhibitor to demonstrate an overall survival benefit at five years in men with metastatic hormone-sensitive prostate cancer
Data continue to show wide-ranging effect of treatment with XTANDI (enzalutamide) plus ADT across various patient subgroups, notably those with high-volume disease, no prior docetaxel use, and synchronous disease
Long-term data reinforce XTANDI (enzalutamide) plus ADT as a standard of care
TOKYO and NEW YORK, May 22, 2025 /PRNewswire/ -- Astellas Pharma Inc. (TSE: 4503, President and CEO: Naoki Okamura, "Astellas") and Pfizer Inc. (NYSE: PFE) today announced longer-term follow-up results from an open-label extension of the Phase 3 ARCHES (NCT02677896) study, reporting a five-year follow up of overall survival (OS) benefits and a 30% reduction in the risk of death in men with metastatic hormone-sensitive prostate cancer (mHSPC) treated with XTANDI™ (enzalutamide), an androgen receptor pathway inhibitor (ARPI), plus androgen deprivation therapy (ADT) compared to placebo plus ADT. These data will be presented during an oral presentation (Abstract #5005) at the American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago (Tuesday, June 3, 9:45 a.m.- 12:45 p.m. US CT).
"Historically, the likelihood of survival at five years for men with metastatic hormone-sensitive prostate cancer was low, but with advancements in initial treatment intensification like what we've seen with XTANDI, this is now becoming the standard," said Andrew J. Armstrong, MD, ScM, Director of Research at the Center for Prostate & Urologic Cancers, Duke Cancer Institute, Durham, NC, and ARCHES primary investigator. "In our five-year follow up of the global ARCHES trial, two-thirds of men are now surviving five years, representing a 13% absolute and 30% relative improvement over standard hormonal therapy alone, with benefits in patients with high and low disease burden that are meaningful to our patients."
In patients with high-volume disease (HR: 0.70; 95% CI: 0.56-0.88) a 36-month improvement in median OS was observed. Additional clinically relevant subgroups of patients were evaluated, showing consistently improved survival: low-volume disease (HR: 0.71; 95% CI, 0.49-1.05); patients who had previously received docetaxel therapy (HR: 0.67; 95% CI, 0.43- 1.05) and those who had not received prior docetaxel therapy (HR: 0.71; 95% CI, 0.57-0.88). The incidence of treatment-emergent adverse events in the five-year follow-up is consistent with prior ARCHES analyses and no new safety signals were identified.
"The survival benefits of intervention with XTANDI in advanced prostate cancer are well-recognized," added Shontelle Dodson, Executive Vice President, Head of Medical Affairs, Astellas. "The collective – and growing – body of data for XTANDI continues to reinforce its long-term efficacy and patient impact in prostate cancer, including in the metastatic setting, and shows that XTANDI is changing the trajectory of those living with the disease."
These results of the five-year follow-up from the ARCHES study will be submitted for publication in a peer-reviewed journal in the near future.
"Until recently, patients with metastatic hormone-sensitive prostate cancer faced a poor prognosis, particularly in advanced stages, often due to treatment resistance," said Johanna Bendell, M.D., Oncology Chief Development Officer, Pfizer. "As the only androgen receptor inhibitor demonstrating sustained five-year survival in this patient population, these data further reinforce XTANDI combined with androgen deprivation therapy as the standard-of-care for treating this advanced disease."
In addition to five-year data from the follow-up ARCHES study, eight-year data from the ENZAMET study assessing outcomes of enzalutamide versus non-steroidal anti-androgen (NSAA) – both plus testosterone suppression with or without docetaxel – in mHSPC will also be presented during a poster session at ASCO (Monday, June 2, 9:00 a.m. US CT). This independent, Phase 3 trial sponsored by the University of Sydney (NCT02446405), led by the Australian and New Zealand Urogenital and Prostate Cancer Trials Group Limited (ANZUP), demonstrated a reduction in risk of death in men with mHSPC.
"Data from the eight-year follow-up of XTANDI are highly encouraging, as they show the progression-free survival and overall survival benefits are sustained out to at least eight years," said Christopher Sweeney, MBBS, DHS, FRACP, ANZUP Cancer Trials Group Limited, Sydney, Australia, and ENZAMET follow-up primary investigator. "These results further support the value of XTANDI as a treatment regimen for metastatic hormone-sensitive prostate cancer."
With a median follow-up of 98 months, patients with mHSPC were treated with XTANDI plus testosterone suppression or NSAA plus testosterone suppression, each group with or without docetaxel. The median OS in the XTANDI group was 8.0 years and 5.8 years in the NSAA group (HR: 0.73; 95% CI, 0.63-0.86). OS at 96 months was 50% with XTANDI and 40% for NSAA; progression-free survival (PFS) also favored XTANDI over NSAA (HR: 0.49; 95% CI, 0.42-0.57). Prostate cancer accounted for 468 of all 622 deaths and were less frequent among those assigned XTANDI than NSAA (207 versus 261). Other causes accounted for a total of 154 deaths and were similarly frequent among those assigned XTANDI versus NSAA (78 versus 76). Mean duration of treatment was longer for XTANDI (58 months) than NSAA (36 months), with 33% remaining on XTANDI and 88% of these patients remained at the full dose of 160 mg.
XTANDI is currently approved in more than 90 countries, including in the United States, European Union and Japan. Since its initial approval in 2012, over one million patients have been treated with XTANDI globally.1***
About Metastatic Hormone-Sensitive Prostate Cancer (mHSPC)
Metastatic hormone-sensitive prostate cancer, also known as metastatic castration-sensitive prostate cancer, refers to prostate cancer that still responds to hormonal therapy and has spread outside of the prostate gland to other parts of the body, such as the lymph nodes, bones, lungs and liver.2
About the ARCHES Study
The Phase 3, randomized, double-blind, placebo-controlled, multi-national trial enrolled 1,150 patients with metastatic hormone-sensitive prostate cancer (mHSPC) at sites in the United States, Canada, Europe, South America and the Asia-Pacific region. Patients in the ARCHES trial were randomized to receive XTANDI 160 mg daily or placebo and continued on a luteinizing hormone-releasing hormone (LHRH) agonist or antagonist or had a history of bilateral orchiectomy. The ARCHES trial included patients with both low- and high-volume disease and both newly diagnosed patients with mHSPC and patients who had prior definitive therapy and subsequently developed metastatic disease. The trial also included some patients who had received recent treatment with docetaxel for mHSPC, but whose disease had not progressed. The primary endpoint of the trial was radiographic progression-free survival (rPFS), defined as the time from randomization to the first objective evidence of radiographic disease progression as assessed by central review, or death within 24 weeks of treatment discontinuation.
In addition to the key secondary endpoint of overall survival at final analysis, a post hoc 5-year analysis was executed with the intent to further quantify long-term overall survival at a clinically meaningful landmark follow-up of five years.
For more information on the global ARCHES trial, go to .
About ENZAMET
ENZAMET is a trial led by ANZUP Cancer Trials Group Limited in collaboration with the NHMRC (National Health and Medical Research Council) Clinical Trials Centre at the University of Sydney with trial sites in Australia, Canada, Ireland, New Zealand, UK and United States. The trial evaluates the potential of enzalutamide plus androgen deprivation therapy (ADT) versus a conventional non-steroidal anti androgen (NSAA) plus ADT in 1,125 men with mHSPC. The primary endpoint for the trial is overall survival (OS). Additional details about ENZAMET (NCT02446405) are available on . Astellas provided funding and support for the ENZAMET trial.
About XTANDI™ (enzalutamide)
XTANDI (enzalutamide) is an androgen receptor signaling inhibitor. XTANDI is a standard of care and has received regulatory approvals in one or more countries around the world for use in men with metastatic hormone-sensitive prostate cancer (mHSPC), metastatic castration-resistant prostate cancer (mCRPC), non-metastatic castration-resistant prostate cancer (nmCRPC) and non-metastatic hormone-sensitive prostate cancer (nmHSPC) with high-risk biochemical recurrence (BCR). XTANDI is currently approved for one or more of these indications in more than 90 countries, including in the United States, European Union and Japan. Over one million patients have been treated with XTANDI globally.1
About XTANDI (enzalutamide) and Important Safety Information
XTANDI (enzalutamide) is indicated for the treatment of patients with:
castration-resistant prostate cancer (CRPC)
metastatic castration-sensitive prostate cancer (mCSPC)
nonmetastatic castration sensitive prostate cancer (nmCSPC) with biochemical recurrence at high risk for metastasis (high-risk BCR)
Important Safety Information
Warnings and Precautions
Seizure occurred in 0.6% of patients receiving XTANDI in eight randomized clinical trials. In a study of patients with predisposing factors for seizure, 2.2% of XTANDI-treated patients experienced a seizure. It is unknown whether anti-epileptic medications will prevent seizures with XTANDI. Patients in the study had one or more of the following predisposing factors: use of medications that may lower the seizure threshold, history of traumatic brain or head injury, history of cerebrovascular accident or transient ischemic attack, and Alzheimer's disease, meningioma, or leptomeningeal disease from prostate cancer, unexplained loss of consciousness within the last 12 months, history of seizure, presence of a space occupying lesion of the brain, history of arteriovenous malformation, or history of brain infection. Advise patients of the risk of developing a seizure while taking XTANDI and of engaging in any activity where sudden loss of consciousness could cause serious harm to themselves or others. Permanently discontinue XTANDI in patients who develop a seizure during treatment.
Posterior Reversible Encephalopathy Syndrome (PRES) There have been reports of PRES in patients receiving XTANDI. PRES is a neurological disorder that can present with rapidly evolving symptoms including seizure, headache, lethargy, confusion, blindness, and other visual and neurological disturbances, with or without associated hypertension. A diagnosis of PRES requires confirmation by brain imaging, preferably MRI. Discontinue XTANDI in patients who develop PRES.
Hypersensitivity reactions, including edema of the face (0.5%), tongue (0.1%), or lip (0.1%) have been observed with XTANDI in eight randomized clinical trials. Pharyngeal edema has been reported in post-marketing cases. Advise patients who experience any symptoms of hypersensitivity to temporarily discontinue XTANDI and promptly seek medical care. Permanently discontinue XTANDI for serious hypersensitivity reactions.
Ischemic Heart Disease In the combined data of five randomized, placebo-controlled clinical studies, ischemic heart disease occurred more commonly in patients on the XTANDI arm compared to patients on the placebo arm (3.5% vs 2%). Grade 3-4 ischemic events occurred in 1.8% of patients on XTANDI versus 1.1% on placebo. Ischemic events led to death in 0.4% of patients on XTANDI compared to 0.1% on placebo. Monitor for signs and symptoms of ischemic heart disease. Optimize management of cardiovascular risk factors, such as hypertension, diabetes, or dyslipidemia. Discontinue XTANDI for Grade 3-4 ischemic heart disease.
Falls and Fractures occurred in patients receiving XTANDI. Evaluate patients for fracture and fall risk. Monitor and manage patients at risk for fractures according to established treatment guidelines and consider use of bone-targeted agents. In the combined data of five randomized, placebo-controlled clinical studies, falls occurred in 12% of patients treated with XTANDI compared to 6% of patients treated with placebo. Fractures occurred in 13% of patients treated with XTANDI and in 6% of patients treated with placebo.
Embryo-Fetal Toxicity The safety and efficacy of XTANDI have not been established in females. XTANDI can cause fetal harm and loss of pregnancy when administered to a pregnant female. Advise males with female partners of reproductive potential to use effective contraception during treatment with XTANDI and for 3 months after the last dose of XTANDI.
Dysphagia or Choking Severe dysphagia or choking, including events that could be life-threatening requiring medical intervention or fatal, can occur due to XTANDI product size. Advise patients to take each capsule or tablet whole with a sufficient amount of water to ensure that all medication is successfully swallowed. Consider use of a smaller tablet size of XTANDI in patients who have difficulty swallowing. Discontinue XTANDI for patients who cannot swallow capsules or tablets.
Adverse Reactions (ARs)
In the data from the five randomized placebo-controlled trials, the most common ARs (≥ 10%) that occurred more frequently (≥ 2% over placebo) in XTANDI-treated patients were musculoskeletal pain, fatigue, hot flush, constipation, decreased appetite, diarrhea, hypertension, hemorrhage, fall, fracture, and headache. In the bicalutamide-controlled study, the most common ARs (≥ 10%) reported in XTANDI-treated patients were asthenia/fatigue, back pain, musculoskeletal pain, hot flush, hypertension, nausea, constipation, diarrhea, upper respiratory tract infection, and weight loss.
In ARCHES, the placebo-controlled study of metastatic CSPC (mCSPC) patients, Grade 3 or higher ARs were reported in 24% of XTANDI-treated patients. Permanent discontinuation due to ARs as the primary reason was reported in 5% of XTANDI patients and 4% of placebo patients.
Lab Abnormalities: Lab abnormalities that occurred in ≥ 5% of patients, and more frequently (> 2%) in the XTANDI arm compared to placebo in the pooled, randomized, placebo-controlled studies are hemoglobin decrease, neutrophil count decreased, white blood cell decreased, hyperglycemia, hypermagnesemia, hyponatremia, hypophosphatemia, and hypercalcemia.
Hypertension: In the combined data from five randomized placebo-controlled clinical trials, hypertension was reported in 14.2% of XTANDI patients and 7.4% of placebo patients. Hypertension led to study discontinuation in < 1% of patients in each arm.
Drug Interactions
Effect of Other Drugs on XTANDI Avoid coadministration with strong CYP2C8 inhibitors. If coadministration cannot be avoided, reduce the dosage of XTANDI.
Avoid coadministration with strong CYP3A4 inducers. If coadministration cannot be avoided, increase the dosage of XTANDI.
Effect of XTANDI on Other Drugs Avoid coadministration with certain CYP3A4, CYP2C9, and CYP2C19 substrates for which minimal decrease in concentration may lead to therapeutic failure of the substrate. If coadministration cannot be avoided, increase the dosage of these substrates in accordance with their Prescribing Information. In cases where active metabolites are formed, there may be increased exposure to the active metabolites.
About Astellas
Astellas Pharma Inc. is a pharmaceutical company conducting business in more than 70 countries around the world. We are promoting the Focus Area Approach that is designed to identify opportunities for the continuous creation of new drugs to address diseases with high unmet medical needs by focusing on Biology and Modality. Furthermore, we are also looking beyond our foundational Rx focus to create Rx+® healthcare solutions that combine our expertise and knowledge with cutting-edge technology in different fields of external partners. Through these efforts, Astellas stands on the forefront of healthcare change to turn innovative science into VALUE for patients. For more information, please visit our website at .
About Pfizer Oncology
At Pfizer Oncology, we are at the forefront of a new era in cancer care. Our industry-leading portfolio and extensive pipeline includes three core mechanisms of action to attack cancer from multiple angles, including small molecules, antibody-drug conjugates (ADCs), and bispecific antibodies, including other immune-oncology biologics. We are focused on delivering transformative therapies in some of the world's most common cancers, including breast cancer, genitourinary cancer, hematology-oncology, and thoracic cancers, which includes lung cancer. Driven by science, we are committed to accelerating breakthroughs to help people with cancer live better and longer lives.
About the Pfizer/Astellas Collaboration
In October 2009, Medivation, Inc., which is now part of Pfizer (NYSE: PFE), and Astellas (TSE: 4503) entered into a global agreement to jointly develop and commercialize XTANDI (enzalutamide). The companies jointly commercialize XTANDI in the United States, and Astellas has responsibility for manufacturing and all additional regulatory filings globally, as well as commercializing XTANDI outside the United States.
Astellas Forward-Looking Statement
In this press release, statements made with respect to current plans, estimates, strategies and beliefs and other statements that are not historical facts are forward-looking statements about the future performance of Astellas. These statements are based on management's current assumptions and beliefs in light of the information currently available to it and involve known and unknown risks and uncertainties. A number of factors could cause actual results to differ materially from those discussed in the forward-looking statements. Such factors include, but are not limited to: (i) changes in general economic conditions and in laws and regulations, relating to pharmaceutical markets, (ii) currency exchange rate fluctuations, (iii) delays in new product launches, (iv) the inability of Astellas to market existing and new products effectively, (v) the inability of Astellas to continue to effectively research and develop products accepted by customers in highly competitive markets, and (vi) infringements of Astellas' intellectual property rights by third parties.
Information about pharmaceutical products (including products currently in development), which is included in this press release is not intended to constitute an advertisement or medical advice.
Pfizer Disclosure Notice
The information contained in this release is as of May 22, 2025. Pfizer assumes no obligation to update forward-looking statements contained in this release as the result of new information or future events or developments.
This release contains forward-looking information about XTANDI (enzalutamide) and a new indication in the U.S. for the treatment of patients with nonmetastatic castration-sensitive prostate cancer with biochemical recurrence at high risk for metastasis (high-risk BCR), including their potential benefits, that involves substantial risks and uncertainties that could cause actual results to differ materially from those expressed or implied by such statements. Risks and uncertainties include, among other things, uncertainties regarding the commercial success of XTANDI; the uncertainties inherent in research and development, including the ability to meet anticipated clinical endpoints, commencement and/or completion dates for clinical trials, regulatory submission dates, regulatory approval dates and/or launch dates, as well as the possibility of unfavorable new clinical data and further analyses of existing clinical data; whether the EMBARK trial will meet the secondary endpoint of overall survival; the risk that clinical trial data are subject to differing interpretations and assessments by regulatory authorities; whether regulatory authorities will be satisfied with the design of and results from the clinical studies; whether and when drug applications for XTANDI may be filed in other jurisdictions; whether and when regulatory authorities in any jurisdictions may approve any such applications that may be pending or filed for XTANDI (including the application pending with the European Medicines Agency), which will depend on a myriad of factors, including making a determination as to whether the product's benefits outweigh its known risks and determination of the product's efficacy and, if approved, whether XTANDI for any potential indication will be commercially successful; decisions by regulatory authorities impacting labeling, manufacturing processes, safety, and/or other matters that could affect the availability or commercial potential of XTANDI, including for the new indication; dependence on the efforts and funding by Astellas Pharma Inc. for the development, manufacturing and commercialization of XTANDI; uncertainties regarding the impact of COVID-19 on Pfizer's business, operations and financial results; and competitive developments.
A further description of risks and uncertainties can be found in Pfizer's Annual Report on Form 10-K for the fiscal year ended December 31, 2024, and in its subsequent reports on Form 10-Q, including in the sections thereof captioned "Risk Factors" and "Forward-Looking Information and Factors That May Affect Future Results", as well as in its subsequent reports on Form 8-K, all of which are filed with the U.S. Securities and Exchange Commission and available at and .
Astellas Cautionary Notes
In this press release, statements made with respect to current plans, estimates, strategies and beliefs and other statements that are not historical facts are forward-looking statements about the future performance of Astellas. These statements are based on management's current assumptions and beliefs in light of the information currently available to it and involve known and unknown risks and uncertainties. A number of factors could cause actual results to differ materially from those discussed in the forward-looking statements. Such factors include, but are not limited to: (i) changes in general economic conditions and in laws and regulations, relating to pharmaceutical markets, (ii) currency exchange rate fluctuations, (iii) delays in new product launches, (iv) the inability of Astellas to market existing and new products effectively, (v) the inability of Astellas to continue to effectively research and develop products accepted by customers in highly competitive markets, and (vi) infringements of Astellas' intellectual property rights by third parties.
Information about pharmaceutical products (including products currently in development) which is included in this press release is not intended to constitute an advertisement or medical advice.
1 Astellas. Data on File. XTANDI patient. January 2023.
2 Sartor, O., de Bono, J., Chi, K. N., Fizazi, K., Herrmann, K., Piulats, J. M., ... & Hussain, M. (2021). Lutetium-177-PSMA-617 for Metastatic Castration-Resistant Prostate Cancer. New England Journal of Medicine, 385(12), 1091-1103.
SOURCE Astellas Pharma Inc.
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临床结果临床3期上市批准ASCO会议
2025-05-22
Five-year follow-up data from the Phase 3 ARCHES trial shows XTANDI (enzalutamide) plus androgen deprivation therapy (ADT) reduces risk of death by 30% After a median follow-up of 61.4 months, treatment with XTANDI (enzalutamide) plus ADT was associated with a 66% probability of survival at five years compared to 53% probability of survival with placebo plus ADT XTANDI (enzalutamide) is the first and only androgen receptor inhibitor to demonstrate an overall survival benefit at five years in men with metastatic hormone-sensitive prostate cancer Data continue to show wide-ranging effect of treatment with XTANDI (enzalutamide) plus ADT across various patient subgroups, notably those with high-volume disease, no prior docetaxel use, and synchronous disease Long-term data reinforce XTANDI (enzalutamide) plus ADT as a standard of care
TOKYO and NEW YORK, May 22, 2025 — Astellas Pharma Inc. (TSE: 4503, President and CEO: Naoki Okamura, “Astellas”) and Pfizer Inc. (NYSE: PFE) today announced longer-term follow-up results from an open-label extension of the Phase 3 ARCHES (NCT02677896) study, reporting a five-year follow up of overall survival (OS) benefits and a 30% reduction in the risk of death in men with metastatic hormone-sensitive prostate cancer (mHSPC) treated with XTANDI™ (enzalutamide), an androgen receptor pathway inhibitor (ARPI), plus androgen deprivation therapy (ADT) compared to placebo plus ADT. These data will be presented during an oral presentation (Abstract #5005) at the American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago (Tuesday, June 3, 9:45 a.m.- 12:45 p.m. US CT).
“Historically, the likelihood of survival at five years for men with metastatic hormone-sensitive prostate cancer was low, but with advancements in initial treatment intensification like what we’ve seen with XTANDI, this is now becoming the standard,” said Andrew J. Armstrong, MD, ScM, Director of Research at the Center for Prostate & Urologic Cancers, Duke Cancer Institute, Durham, NC, and ARCHES primary investigator. “In our five-year follow up of the global ARCHES trial, two-thirds of men are now surviving five years, representing a 13% absolute and 30% relative improvement over standard hormonal therapy alone, with benefits in patients with high and low disease burden that are meaningful to our patients.”
In patients with high-volume disease (HR: 0.70; 95% CI: 0.56-0.88) a 36-month improvement in median OS was observed. Additional clinically relevant subgroups of patients were evaluated, showing consistently improved survival: low-volume disease (HR: 0.71; 95% CI, 0.49-1.05); patients who had previously received docetaxel therapy (HR: 0.67; 95% CI, 0.43- 1.05) and those who had not received prior docetaxel therapy (HR: 0.71; 95% CI, 0.57-0.88). The incidence of treatment-emergent adverse events in the five-year follow-up is consistent with prior ARCHES analyses and no new safety signals were identified.
“The survival benefits of intervention with XTANDI in advanced prostate cancer are well-recognized,” added Shontelle Dodson, Executive Vice President, Head of Medical Affairs, Astellas. “The collective – and growing – body of data for XTANDI continues to reinforce its long-term efficacy and patient impact in prostate cancer, including in the metastatic setting, and shows that XTANDI is changing the trajectory of those living with the disease.”
These results of the five-year follow-up from the ARCHES study will be submitted for publication in a peer-reviewed journal in the near future.
“Until recently, patients with metastatic hormone-sensitive prostate cancer faced a poor prognosis, particularly in advanced stages, often due to treatment resistance,” said Johanna Bendell, M.D., Oncology Chief Development Officer, Pfizer. “As the only androgen receptor inhibitor demonstrating sustained five-year survival in this patient population, these data further reinforce XTANDI combined with androgen deprivation therapy as the standard-of-care for treating this advanced disease.”
In addition to five-year data from the follow-up ARCHES study, eight-year data from the ENZAMET study assessing outcomes of enzalutamide versus non-steroidal anti-androgen (NSAA) – both plus testosterone suppression with or without docetaxel – in mHSPC will also be presented during a poster session at ASCO (Monday, June 2, 9:00 a.m. US CT). This independent, Phase 3 trial sponsored by the University of Sydney (NCT02446405), led by the Australian and New Zealand Urogenital and Prostate Cancer Trials Group Limited (ANZUP), demonstrated a reduction in risk of death in men with mHSPC.
“Data from the eight-year follow-up of XTANDI are highly encouraging, as they show the progression-free survival and overall survival benefits are sustained out to at least eight years,” said Christopher Sweeney, MBBS, DHS, FRACP, ANZUP Cancer Trials Group Limited, Sydney, Australia, and ENZAMET follow-up primary investigator. “These results further support the value of XTANDI as a treatment regimen for metastatic hormone-sensitive prostate cancer.”
With a median follow-up of 98 months, patients with mHSPC were treated with XTANDI plus testosterone suppression or NSAA plus testosterone suppression, each group with or without docetaxel. The median OS in the XTANDI group was 8.0 years and 5.8 years in the NSAA group (HR: 0.73; 95% CI, 0.63-0.86). OS at 96 months was 50% with XTANDI and 40% for NSAA; progression-free survival (PFS) also favored XTANDI over NSAA (HR: 0.49; 95% CI, 0.42-0.57). Prostate cancer accounted for 468 of all 622 deaths and were less frequent among those assigned XTANDI than NSAA (207 versus 261). Other causes accounted for a total of 154 deaths and were similarly frequent among those assigned XTANDI versus NSAA (78 versus 76). Mean duration of treatment was longer for XTANDI (58 months) than NSAA (36 months), with 33% remaining on XTANDI and 88% of these patients remained at the full dose of 160 mg.
XTANDI is currently approved in more than 90 countries, including in the United States, European Union and Japan. Since its initial approval in 2012, over one million patients have been treated with XTANDI globally.1
***
About Metastatic Hormone-Sensitive Prostate Cancer (mHSPC) Metastatic hormone-sensitive prostate cancer, also known as metastatic castration-sensitive prostate cancer, refers to prostate cancer that still responds to hormonal therapy and has spread outside of the prostate gland to other parts of the body, such as the lymph nodes, bones, lungs and liver.2
About the ARCHES Study The Phase 3, randomized, double-blind, placebo-controlled, multi-national trial enrolled 1,150 patients with metastatic hormone-sensitive prostate cancer (mHSPC) at sites in the United States, Canada, Europe, South America and the Asia-Pacific region. Patients in the ARCHES trial were randomized to receive XTANDI 160 mg daily or placebo and continued on a luteinizing hormone-releasing hormone (LHRH) agonist or antagonist or had a history of bilateral orchiectomy. The ARCHES trial included patients with both low- and high-volume disease and both newly diagnosed patients with mHSPC and patients who had prior definitive therapy and subsequently developed metastatic disease. The trial also included some patients who had received recent treatment with docetaxel for mHSPC, but whose disease had not progressed. The primary endpoint of the trial was radiographic progression-free survival (rPFS), defined as the time from randomization to the first objective evidence of radiographic disease progression as assessed by central review, or death within 24 weeks of treatment discontinuation.
In addition to the key secondary endpoint of overall survival at final analysis, a post hoc 5-year analysis was executed with the intent to further quantify long-term overall survival at a clinically meaningful landmark follow-up of five years.
For more information on the global ARCHES trial, go to www.clinicaltrials.gov.
About ENZAMET ENZAMET is a trial led by ANZUP Cancer Trials Group Limited in collaboration with the NHMRC (National Health and Medical Research Council) Clinical Trials Centre at the University of Sydney with trial sites in Australia, Canada, Ireland, New Zealand, UK and United States. The trial evaluates the potential of enzalutamide plus androgen deprivation therapy (ADT) versus a conventional non-steroidal anti androgen (NSAA) plus ADT in 1,125 men with mHSPC. The primary endpoint for the trial is overall survival (OS). Additional details about ENZAMET (NCT02446405) are available on www.clinicaltrials.gov. Astellas provided funding and support for the ENZAMET trial.
About XTANDI™ (enzalutamide) XTANDI (enzalutamide) is an androgen receptor signaling inhibitor. XTANDI is a standard of care and has received regulatory approvals in one or more countries around the world for use in men with metastatic hormone-sensitive prostate cancer (mHSPC), metastatic castration-resistant prostate cancer (mCRPC), non-metastatic castration-resistant prostate cancer (nmCRPC) and non-metastatic hormone-sensitive prostate cancer (nmHSPC) with high-risk biochemical recurrence (BCR). XTANDI is currently approved for one or more of these indications in more than 90 countries, including in the United States, European Union and Japan. Over one million patients have been treated with XTANDI globally.1
About XTANDI (enzalutamide) and Important Safety Information
XTANDI (enzalutamide) is indicated for the treatment of patients with:
castration-resistant prostate cancer (CRPC) metastatic castration-sensitive prostate cancer (mCSPC) nonmetastatic castration sensitive prostate cancer (nmCSPC) with biochemical recurrence at high risk for metastasis (high-risk BCR)
Important Safety Information
Warnings and Precautions Seizure occurred in 0.6% of patients receiving XTANDI in eight randomized clinical trials. In a study of patients with predisposing factors for seizure, 2.2% of XTANDI-treated patients experienced a seizure. It is unknown whether anti-epileptic medications will prevent seizures with XTANDI. Patients in the study had one or more of the following predisposing factors: use of medications that may lower the seizure threshold, history of traumatic brain or head injury, history of cerebrovascular accident or transient ischemic attack, and Alzheimer’s disease, meningioma, or leptomeningeal disease from prostate cancer, unexplained loss of consciousness within the last 12 months, history of seizure, presence of a space occupying lesion of the brain, history of arteriovenous malformation, or history of brain infection. Advise patients of the risk of developing a seizure while taking XTANDI and of engaging in any activity where sudden loss of consciousness could cause serious harm to themselves or others. Permanently discontinue XTANDI in patients who develop a seizure during treatment.
Posterior Reversible Encephalopathy Syndrome (PRES) There have been reports of PRES in patients receiving XTANDI. PRES is a neurological disorder that can present with rapidly evolving symptoms including seizure, headache, lethargy, confusion, blindness, and other visual and neurological disturbances, with or without associated hypertension. A diagnosis of PRES requires confirmation by brain imaging, preferably MRI. Discontinue XTANDI in patients who develop PRES.
Hypersensitivity reactions, including edema of the face (0.5%), tongue (0.1%), or lip (0.1%) have been observed with XTANDI in eight randomized clinical trials. Pharyngeal edema has been reported in post-marketing cases. Advise patients who experience any symptoms of hypersensitivity to temporarily discontinue XTANDI and promptly seek medical care. Permanently discontinue XTANDI for serious hypersensitivity reactions.
Ischemic Heart Disease In the combined data of five randomized, placebo-controlled clinical studies, ischemic heart disease occurred more commonly in patients on the XTANDI arm compared to patients on the placebo arm (3.5% vs 2%). Grade 3-4 ischemic events occurred in 1.8% of patients on XTANDI versus 1.1% on placebo. Ischemic events led to death in 0.4% of patients on XTANDI compared to 0.1% on placebo. Monitor for signs and symptoms of ischemic heart disease. Optimize management of cardiovascular risk factors, such as hypertension, diabetes, or dyslipidemia. Discontinue XTANDI for Grade 3-4 ischemic heart disease.
Falls and Fractures occurred in patients receiving XTANDI. Evaluate patients for fracture and fall risk. Monitor and manage patients at risk for fractures according to established treatment guidelines and consider use of bone-targeted agents. In the combined data of five randomized, placebo-controlled clinical studies, falls occurred in 12% of patients treated with XTANDI compared to 6% of patients treated with placebo. Fractures occurred in 13% of patients treated with XTANDI and in 6% of patients treated with placebo.
Embryo-Fetal Toxicity The safety and efficacy of XTANDI have not been established in females. XTANDI can cause fetal harm and loss of pregnancy when administered to a pregnant female. Advise males with female partners of reproductive potential to use effective contraception during treatment with XTANDI and for 3 months after the last dose of XTANDI.
Dysphagia or Choking Severe dysphagia or choking, including events that could be life-threatening requiring medical intervention or fatal, can occur due to XTANDI product size. Advise patients to take each capsule or tablet whole with a sufficient amount of water to ensure that all medication is successfully swallowed. Consider use of a smaller tablet size of XTANDI in patients who have difficulty swallowing. Discontinue XTANDI for patients who cannot swallow capsules or tablets.
Adverse Reactions (ARs) In the data from the five randomized placebo-controlled trials, the most common ARs (≥ 10%) that occurred more frequently (≥ 2% over placebo) in XTANDI-treated patients were musculoskeletal pain, fatigue, hot flush, constipation, decreased appetite, diarrhea, hypertension, hemorrhage, fall, fracture, and headache. In the bicalutamide-controlled study, the most common ARs (≥ 10%) reported in XTANDI-treated patients were asthenia/fatigue, back pain, musculoskeletal pain, hot flush, hypertension, nausea, constipation, diarrhea, upper respiratory tract infection, and weight loss.
In ARCHES, the placebo-controlled study of metastatic CSPC (mCSPC) patients, Grade 3 or higher ARs were reported in 24% of XTANDI-treated patients. Permanent discontinuation due to ARs as the primary reason was reported in 5% of XTANDI patients and 4% of placebo patients. Lab Abnormalities: Lab abnormalities that occurred in ≥ 5% of patients, and more frequently (> 2%) in the XTANDI arm compared to placebo in the pooled, randomized, placebo-controlled studies are hemoglobin decrease, neutrophil count decreased, white blood cell decreased, hyperglycemia, hypermagnesemia, hyponatremia, hypophosphatemia, and hypercalcemia.
Hypertension: In the combined data from five randomized placebo-controlled clinical trials, hypertension was reported in 14.2% of XTANDI patients and 7.4% of placebo patients. Hypertension led to study discontinuation in < 1% of patients in each arm.
Drug Interactions Effect of Other Drugs on XTANDI Avoid coadministration with strong CYP2C8 inhibitors. If coadministration cannot be avoided, reduce the dosage of XTANDI.
Avoid coadministration with strong CYP3A4 inducers. If coadministration cannot be avoided, increase the dosage of XTANDI.
Effect of XTANDI on Other Drugs Avoid coadministration with certain CYP3A4, CYP2C9, and CYP2C19 substrates for which minimal decrease in concentration may lead to therapeutic failure of the substrate. If coadministration cannot be avoided, increase the dosage of these substrates in accordance with their Prescribing Information. In cases where active metabolites are formed, there may be increased exposure to the active metabolites.
About Astellas Astellas Pharma Inc. is a pharmaceutical company conducting business in more than 70 countries around the world. We are promoting the Focus Area Approach that is designed to identify opportunities for the continuous creation of new drugs to address diseases with high unmet medical needs by focusing on Biology and Modality. Furthermore, we are also looking beyond our foundational Rx focus to create Rx+® healthcare solutions that combine our expertise and knowledge with cutting-edge technology in different fields of external partners. Through these efforts, Astellas stands on the forefront of healthcare change to turn innovative science into VALUE for patients. For more information, please visit our website at https://www.astellas.com/en.
About Pfizer Oncology At Pfizer Oncology, we are at the forefront of a new era in cancer care. Our industry-leading portfolio and extensive pipeline includes three core mechanisms of action to attack cancer from multiple angles, including small molecules, antibody-drug conjugates (ADCs), and bispecific antibodies, including other immune-oncology biologics. We are focused on delivering transformative therapies in some of the world’s most common cancers, including breast cancer, genitourinary cancer, hematology-oncology, and thoracic cancers, which includes lung cancer. Driven by science, we are committed to accelerating breakthroughs to help people with cancer live better and longer lives.
About the Pfizer/Astellas Collaboration In October 2009, Medivation, Inc., which is now part of Pfizer (NYSE: PFE), and Astellas (TSE: 4503) entered into a global agreement to jointly develop and commercialize XTANDI (enzalutamide). The companies jointly commercialize XTANDI in the United States, and Astellas has responsibility for manufacturing and all additional regulatory filings globally, as well as commercializing XTANDI outside the United States.
Astellas Forward-Looking Statement In this press release, statements made with respect to current plans, estimates, strategies and beliefs and other statements that are not historical facts are forward-looking statements about the future performance of Astellas. These statements are based on management’s current assumptions and beliefs in light of the information currently available to it and involve known and unknown risks and uncertainties. A number of factors could cause actual results to differ materially from those discussed in the forward-looking statements. Such factors include, but are not limited to: (i) changes in general economic conditions and in laws and regulations, relating to pharmaceutical markets, (ii) currency exchange rate fluctuations, (iii) delays in new product launches, (iv) the inability of Astellas to market existing and new products effectively, (v) the inability of Astellas to continue to effectively research and develop products accepted by customers in highly competitive markets, and (vi) infringements of Astellas’ intellectual property rights by third parties.
Information about pharmaceutical products (including products currently in development), which is included in this press release is not intended to constitute an advertisement or medical advice.
Pfizer Disclosure Notice The information contained in this release is as of May 22, 2025. Pfizer assumes no obligation to update forward-looking statements contained in this release as the result of new information or future events or developments.
This release contains forward-looking information about XTANDI (enzalutamide) and a new indication in the U.S. for the treatment of patients with nonmetastatic castration-sensitive prostate cancer with biochemical recurrence at high risk for metastasis (high-risk BCR), including their potential benefits, that involves substantial risks and uncertainties that could cause actual results to differ materially from those expressed or implied by such statements. Risks and uncertainties include, among other things, uncertainties regarding the commercial success of XTANDI; the uncertainties inherent in research and development, including the ability to meet anticipated clinical endpoints, commencement and/or completion dates for clinical trials, regulatory submission dates, regulatory approval dates and/or launch dates, as well as the possibility of unfavorable new clinical data and further analyses of existing clinical data; whether the EMBARK trial will meet the secondary endpoint of overall survival; the risk that clinical trial data are subject to differing interpretations and assessments by regulatory authorities; whether regulatory authorities will be satisfied with the design of and results from the clinical studies; whether and when drug applications for XTANDI may be filed in other jurisdictions; whether and when regulatory authorities in any jurisdictions may approve any such applications that may be pending or filed for XTANDI (including the application pending with the European Medicines Agency), which will depend on a myriad of factors, including making a determination as to whether the product’s benefits outweigh its known risks and determination of the product’s efficacy and, if approved, whether XTANDI for any potential indication will be commercially successful; decisions by regulatory authorities impacting labeling, manufacturing processes, safety, and/or other matters that could affect the availability or commercial potential of XTANDI, including for the new indication; dependence on the efforts and funding by Astellas Pharma Inc. for the development, manufacturing and commercialization of XTANDI; uncertainties regarding the impact of COVID-19 on Pfizer’s business, operations and financial results; and competitive developments.
A further description of risks and uncertainties can be found in Pfizer’s Annual Report on Form 10-K for the fiscal year ended December 31, 2024, and in its subsequent reports on Form 10-Q, including in the sections thereof captioned “Risk Factors” and “Forward-Looking Information and Factors That May Affect Future Results”, as well as in its subsequent reports on Form 8-K, all of which are filed with the U.S. Securities and Exchange Commission and available at www.sec.gov and www.pfizer.com.
Astellas Cautionary Notes In this press release, statements made with respect to current plans, estimates, strategies and beliefs and other statements that are not historical facts are forward-looking statements about the future performance of Astellas. These statements are based on management's current assumptions and beliefs in light of the information currently available to it and involve known and unknown risks and uncertainties. A number of factors could cause actual results to differ materially from those discussed in the forward-looking statements. Such factors include, but are not limited to: (i) changes in general economic conditions and in laws and regulations, relating to pharmaceutical markets, (ii) currency exchange rate fluctuations, (iii) delays in new product launches, (iv) the inability of Astellas to market existing and new products effectively, (v) the inability of Astellas to continue to effectively research and develop products accepted by customers in highly competitive markets, and (vi) infringements of Astellas' intellectual property rights by third parties.
Information about pharmaceutical products (including products currently in development) which is included in this press release is not intended to constitute an advertisement or medical advice.
###
1 Astellas. Data on File. XTANDI patient. January 2023. 2 Sartor, O., de Bono, J., Chi, K. N., Fizazi, K., Herrmann, K., Piulats, J. M., ... & Hussain, M. (2021). Lutetium-177-PSMA-617 for Metastatic Castration-Resistant Prostate Cancer. New England Journal of Medicine, 385(12), 1091-1103.
Pfizer Contacts: For Media 212-733-1226 PfizerMediaRelations@Pfizer.com
For Investors 212-733-4848 IR@pfizer.com
Astellas Contacts: For Media +1-847-686-1813 tara.grayczyk@astellas.com
Corporate Communications +81-3-3244-3201
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| 转移性前列腺癌 | 美国 | 1995-10-04 | |
| 前列腺癌 | 英国 | 1995-02-23 |
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| 男子乳腺发育 | 临床3期 | 意大利 | 2003-12-01 | |
| 非转移性前列腺癌 | 临床3期 | 美国 | 1995-08-01 | |
| 非转移性前列腺癌 | 临床3期 | 加拿大 | 1995-08-01 | |
| 晚期前列腺癌 | 临床3期 | 美国 | 1994-12-01 | |
| 转移性乳腺癌 | 临床2期 | 美国 | 2007-03-23 | |
| 近端肾小管性酸中毒伴有眼部异常和智力低下 | 临床2期 | 美国 | 2007-03-23 | |
| 家族性睾丸毒症 | 临床2期 | 美国 | 2004-11-22 | |
| 家族性睾丸毒症 | 临床2期 | 加拿大 | 2004-11-22 | |
| 家族性睾丸毒症 | 临床2期 | 法国 | 2004-11-22 | |
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| 研究 | 分期 | 人群特征 | 评价人数 | 分组 | 结果 | 评价 | 发布日期 |
|---|
临床2期 | 29 | 願範願鹽襯壓範獵遞壓(構範製襯廠壓繭夢鹽壓) = 願鹽網顧築壓網遞範夢 蓋艱鹽鬱鹹築網窪衊簾 (窪糧襯鹹膚構繭獵構艱 ) 更多 | 不佳 | 2024-09-16 | |||
願範願鹽襯壓範獵遞壓(構範製襯廠壓繭夢鹽壓) = 鑰選鹽夢鏇憲膚艱簾積 蓋艱鹽鬱鹹築網窪衊簾 (窪糧襯鹹膚構繭獵構艱 ) 更多 | |||||||
ESMO2024 人工标引  | N/A | AR阳性唾液腺肿瘤 AR Positive | 20 | 鑰遞觸襯積選淵襯夢鏇(製窪鹹膚鏇繭簾襯衊鏇) = 願願鏇鏇窪壓築鹹簾憲 襯蓋醖膚構淵構獵鑰鹹 (觸壓顧網築艱憲鬱觸網, 0.5 ~ 62.5) 更多 | 积极 | 2024-09-14 | |
N/A | - | 窪鬱獵壓夢壓觸範顧觸(艱窪鬱醖簾鹹鹹壓鹽膚) = pH 7.42, PCO2 32, and PO2 66 鹹鏇鑰膚觸範顧衊築網 (願顧遞鏇夢壓壓憲願窪 ) 更多 | - | 2024-05-19 | |||
AUA2024 人工标引 | 临床2期 | 去势抵抗性前列腺癌 ERBB3 Expression | 28 | 簾蓋夢願蓋鹹窪糧網鹽(鹽糧簾顧繭遞製網願憲) = Patients with higher serum levels of ErbB3 exhibited a better response to the bicalutamide+RAD001 treatment 積鏇窪觸鏇獵窪憲築鹽 (顧鬱鑰餘鬱願製選夢製 ) 更多 | 积极 | 2024-05-01 | |
临床2期 | 345 | GnRH + Bicalutamide | 蓋膚衊淵顧壓選壓鬱醖(願選壓淵鏇鬱願遞網繭) = 醖膚襯醖簾齋鹽齋齋醖 淵糧願襯鬱鏇廠遞願艱 (衊襯餘糧鑰鬱鏇構構餘 ) 更多 | 积极 | 2024-01-25 | ||
蓋膚衊淵顧壓選壓鬱醖(願選壓淵鏇鬱願遞網繭) = 構築鏇願鬱糧網艱蓋獵 淵糧願襯鬱鏇廠遞願艱 (衊襯餘糧鑰鬱鏇構構餘 ) 更多 | |||||||
临床3期 | 760 | RT + bicalutamide | 繭築選築遞夢選構範淵(鑰醖願蓋壓壓餘網獵繭) = 蓋簾蓋廠鬱壓遞製鏇選 餘築膚構衊積艱積襯鹽 (鬱鏇艱鹹積壓觸壓齋網, 47 ~ 58) 更多 | 积极 | 2024-01-25 | ||
RT + placebo | 繭築選築遞夢選構範淵(鑰醖願蓋壓壓餘網獵繭) = 網製夢簾鹹蓋淵憲鏇醖 餘築膚構衊積艱積襯鹽 (鬱鏇艱鹹積壓觸壓齋網, 38 ~ 48) 更多 | ||||||
N/A | - | 積範蓋淵餘獵構範鹹齋(鏇鑰獵窪繭鹽衊構糧獵) = 鏇選壓觸鑰顧襯鬱築繭 艱觸憲廠夢襯選壓鬱網 (窪壓觸糧網鑰廠憲鬱範 ) 更多 | - | 2024-01-25 | |||
临床2期 | - | 構構衊製獵鑰醖繭顧膚(鹹齋夢鑰膚淵鹽淵憲廠): HR = 0.71 (90% CI, 0.49 ~ 1.03), P-Value = 0.06 更多 | 积极 | 2023-10-01 | |||
Abiraterone Acetate/Prednisone (AAP) and Apalutamide (Apa) | |||||||
临床2期 | 26 | 淵積廠繭簾鹹窪鏇廠窪(蓋膚鬱衊鏇糧餘壓網鬱) = 窪廠遞窪獵鬱構願壓醖 壓糧衊鏇顧鹹範齋膚襯 (醖鹹鹹壓窪獵築夢簾廠, 夢憲衊選膚蓋鹽醖淵衊 ~ 衊衊憲遞網膚願範網積) 更多 | - | 2023-02-16 | |||
N/A | 5,336 | (Standard of care (SOC) + ADT) | 繭製鹽構鬱繭範獵遞廠(壓襯壓製構膚淵廠憲膚): HR = 0.83 (95% CI, 0.72 ~ 0.96) 更多 | 不佳 | 2022-11-01 | ||
Standard of care (SOC) + Bicalutamide monotherapy (BICmono) |
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