前列腺癌是男性第二大常見癌症，也是全球男性癌症死亡第五大原因，2020年發病人數140萬，死亡人數375,000。轉移性前列腺癌與顯著的死亡率相關。前列腺癌的發展通常由稱為雄激素的男性性激素驅動，包括睾丸激素。在美國，2022年估計有268,490例新發患者和34,500人死亡。mCRPC患者的總生存期在臨床研究中約為三年，在真實世界中甚至更短。大約一半的mCRPC患者可能隻接受過一線有效治療，後續治療效果會越來越差。

        在mCRPC患者中，盡管使用雄激素剝奪療法來阻斷雄性激素的作用，但前列腺癌仍會進展並擴散到身體其他部位。大約10-20%的晚期前列腺癌患者會在五年內進展為去勢抵抗性前列腺癌(CRPC)，其中至少84%的男性在確診CRPC時已經發生了轉移。在診斷為CRPC時沒有轉移的患者中，33%可能在兩年內發生轉移。盡管過去十多年mCRPC治療因為使用紫杉烷和新型內分泌類藥物(NHA)取得了進展，但該人群的醫療需求未能得到滿足。

        PROpel III期轉移性去勢抵抗性前列腺癌(mCRPC)的最終預設總生存期(OS)分析結果顯示阿斯利康和默沙東聯合開發的奧拉帕利聯合阿比特龍和潑尼鬆/潑尼鬆龍顯示的中位OS為42.1個月，而阿比特龍聯合安慰劑組為34.7個月。顯示聯合治療對比標準治療取得7.4個月的中位OS絕對差異(成熟度47.9%，HR 0.81;95% CI 0.67-1.00;p=0.0544)。

        雖然中位OS未達到統計學差異，但這一臨床活動建立在對照組為患者接受當前的標準治療阿比特龍之上。研究結果將於今天在2023年美國臨床腫瘤學會(ASCO)泌尿生殖係統(GU)癌症研討會(#LBA16)上以口頭報告的形式公布。

        在ASCO GU 2022上報道的研究主要終點結果顯示，PROpel研究達到了主要終點影像學無進展生存(rPFS)，並已發表在《新英格蘭醫學證據雜誌》。結果顯示，奧拉帕利聯合阿比特龍與阿比特龍單藥治療相比，影像學進展或死亡的風險顯著降低了34%(HR 0.66;95% CI 0.54-0.81;p< 0.0001)。

        曼徹斯特克裏斯蒂/索爾福德皇家醫院和曼徹斯特大學泌尿外科醫生兼泌尿腫瘤學教授、PROpel研究高級研究員Noel Clarke表示：“從去年在ASCO GU上展示的主要影像學無進展生存期分析到今天展示的更新後總生存期數據，進一步顯示了奧拉帕利聯合阿比特龍和潑尼鬆對轉移性去勢抵抗性前列腺癌患者在整個研究人群和各亞組的治療潛力。PROpel研究結果對患者和腫瘤學界都非常重要，為這種聯合治療方案提供了支持依據，可作為轉移性去勢抵抗性前列腺癌潛在且急需的新治療選擇。”

        阿斯利康全球執行副總裁，腫瘤治療領域研發負責人Susan Galbraith表示：“奧拉帕利的PARP靶點和雄激素受體對於前列腺癌中DNA修複都很重要。PROpel總體研究人群結果表明，奧拉帕利和阿比特龍聯合治療可以發揮雄激素受體在DNA修複中對PARP的依賴性，提供比阿比特龍單藥更大的抗癌活性。值得注意的是，基於整體數據，在這種情況下聯合治療能為廣大患者帶來治療收益，而近期該適應症在歐盟獲批則進一步強調了這一點。"

        默沙東實驗室全球臨床研究高級副總裁、首席醫學官Eliav Barr博士表示：“前列腺癌是男性患者中第二大最常診斷的癌症，預計未來20年內死亡率將幾乎翻倍。由於這些患者治療選擇有限，我們迫切需要能夠延遲疾病進展的治療方案。我們為與阿斯利康的合作感到自豪，因為我們共同致力於推進有待審批通過的監管審查，並為前列腺癌群體帶來一種新的治療選擇。”

        各亞組關鍵次要總生存期終點的結果摘要

        *18名HRRm狀態未知的患者被排除在亞組分析之外。NR，未達到

        奧拉帕利聯合阿比特龍的安全性和耐受性與之前臨床研究中觀察到的結果以及單藥治療的已知特征一致。在這次更新分析時，沒有發現新的長期安全問題。

        奧拉帕利聯合阿比特龍最常見的不良事件(AEs)(大於或等於20%的患者)是貧血(49.7%)、疲勞(38.7%)、惡心(30.7%)、背痛(21.6%)和腹瀉(20.6%)。在數據截止時，約83%接受奧拉帕利聯合阿比特龍治療並出現不良事件的患者中仍在接受治療。

        2022年12月，歐盟委員會批準奧拉帕利聯合阿比特龍用於治療臨床上未接受過化療的mCRPC成人男性患者，目前正在接受其他國家法規評審。

        注：本文涉及研究中的藥品用法尚未在中國獲批適應症，阿斯利康不推薦任何未被批準的藥品使用。

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