PROpel III 期关键结果：与阿比特龙单药相比，奥拉帕利联合阿比特龙治疗转移性去势抵抗性前列腺癌中位总生存期的绝对差异增加了7.4个月

前列腺癌是男性第二大常见癌症，也是全球男性癌症死亡第五大原因，2020 年发病人数 140 万，死亡人数375,000。转移性前列腺癌与显着的死亡率相关 。前列腺癌的发展通常由称为雄激素的男性性激素驱动，包括睾丸激素。在美国，2022年估计有 268,490 例新发患者和  34,500人死亡。mCRPC患者的总生存期在临床研究中约为三年，在真实世界中甚至更短。 大约一半的 mCRPC 患者可能只接受过一线有效治疗，后续治疗效果会越来越差。

在 mCRPC 患者中，尽管使用雄激素剥夺疗法来阻断雄性激素的作用，但前列腺癌仍会进展并扩散到身体其他部位。大约 10-20% 的晚期前列腺癌患者会在五年内进展为去势抵抗性前列腺癌 (CRPC)，其中至少 84% 的男性在确诊 CRPC 时已经发生了转移。在诊断为CRPC时没有转移的患者中，33% 可能在两年内发生转移。尽管过去十多年 mCRPC 治疗因为使用紫杉烷和新型内分泌类药物（NHA）取得了进展，但该人群的医疗需求未能得到满足。

PROpel III 期转移性去势抵抗性前列腺癌(mCRPC)的最终预设总生存期 (OS) 分析结果显示阿斯利康和默沙东联合开发的奥拉帕利联合阿比特龙和泼尼松/泼尼松龙显示的中位OS为 42.1 个月，而阿比特龙联合安慰剂组为 34.7 个月。显示联合治疗对比标准治疗取得7.4个月的中位OS绝对差异（ 成熟度47.9%， HR 0.81；95% CI 0.67-1.00；p=0.0544）。

虽然中位OS未达到统计学差异，但这一临床活动建立在对照组为患者接受当前的标准治疗阿比特龙之上。研究结果将于今天在 2023 年美国临床肿瘤学会 (ASCO) 泌尿生殖系统 (GU) 癌症研讨会 (#LBA16) 上以口头报告的形式公布。

在ASCO GU 2022上报道的研究主要终点结果显示，PROpel 研究达到了主要终点影像学无进展生存 (rPFS) ，并已发表在《新英格兰医学证据杂志》。结果显示，奥拉帕利联合阿比特龙与阿比特龙单药治疗相比，影像学进展或死亡的风险显著降低了 34%（HR 0.66；95% CI 0.54-0.81；p< 0.0001）。

曼彻斯特克里斯蒂/索尔福德皇家医院和曼彻斯特大学泌尿外科医生兼泌尿肿瘤学教授、PROpel 研究高级研究员 Noel Clarke 表示：“从去年在 ASCO GU 上展示的主要影像学无进展生存期分析到今天展示的更新后总生存期数据，进一步显示了奥拉帕利联合阿比特龙和泼尼松对转移性去势抵抗性前列腺癌患者在整个研究人群和各亚组的治疗潜力。PROpel 研究结果对患者和肿瘤学界都非常重要，为这种联合治疗方案提供了支持依据，可作为转移性去势抵抗性前列腺癌潜在且急需的新治疗选择。”

阿斯利康全球执行副总裁，肿瘤治疗领域研发负责人Susan Galbraith表示：“奥拉帕利的PARP靶点和雄激素受体对于前列腺癌中DNA修复都很重要。PROpel总体研究人群结果表明，奥拉帕利和阿比特龙联合治疗可以发挥雄激素受体在DNA修复中对PARP的依赖性，提供比阿比特龙单药更大的抗癌活性。值得注意的是，基于整体数据，在这种情况下联合治疗能为广大患者带来治疗收益，而近期该适应症在欧盟获批则进一步强调了这一点。"

默沙东实验室全球临床研究高级副总裁、首席医学官Eliav Barr博士表示：“前列腺癌是男性患者中第二大最常诊断的癌症，预计未来20年内死亡率将几乎翻倍。由于这些患者治疗选择有限，我们迫切需要能够延迟疾病进展的治疗方案。我们为与阿斯利康的合作感到自豪，因为我们共同致力于推进有待审批通过的监管审查，并为前列腺癌群体带来一种新的治疗选择。”

各亚组关键次要总生存期终点的结果摘要

*18 名 HRRm 状态未知的患者被排除在亚组分析之外。 NR，未达到

奥拉帕利联合阿比特龙的安全性和耐受性与之前临床研究中观察到的结果以及单药治疗的已知特征一致。 在这次更新分析时，没有发现新的长期安全问题。

奥拉帕利联合阿比特龙最常见的不良事件 (AEs)（大于或等于 20% 的患者）是贫血 (49.7%)、疲劳 (38.7%)、恶心 (30.7%)、背痛 (21.6%) 和腹泻 (20.6%)。 在数据截止时，约83%接受奥拉帕利联合阿比特龙治疗并出现不良事件的患者中仍在接受治疗。

2022年12月，欧盟委员会批准奥拉帕利联合阿比特龙用于治疗临床上未接受过化疗的mCRPC成人男性患者，目前正在接受其他国家法规评审。

注：本文涉及研究中的药品用法尚未在中国获批适应症，阿斯利康不推荐任何未被批准的药品使用。

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