Abiraterone and Olaparib for Metastatic Castration-Resistant Prostate Cancer.
Abiraterone and Olaparib for Metastatic Castration-Resistant Prostate Cancer.
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DOI：
10.1056/evidoa2200043
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发表时间：
2022-09-01
期刊：
影响因子：
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通讯作者：
Saad, Fred
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文献类型：
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作者：
Clarke, Noel W;Armstrong, Andrew J;Saad, Fred
背景：阿比特龙和奥拉帕利的临床前研究和2期试验结果表明，当聚(二磷酸腺苷[ADP]-核糖)聚合酶抑制剂奥拉帕里布与下一代激素剂阿比特龙联合治疗转移性去势抵抗前列腺癌(MCRPC)时，具有联合抗肿瘤作用。方法：我们在一线治疗的mCRPC患者中进行了阿比特龙和奥拉帕利布与阿比特龙和安慰剂的3期双盲试验。患者入选与同源重组修复基因突变(HRRm)状态无关。通过肿瘤组织和循环肿瘤DNA检测确定HRRm状态。患者被随机分配(1：1)接受阿比特龙(1000 mg，每日一次)联合泼尼松或强的松龙与奥拉帕利(300 mg，每日两次)或安慰剂。主要终点是研究者评估的基于影像的无进展生存期(IbPFS)。总体存活率是次要终点之一。结果：在这项计划的初步分析中，在第一个数据截止点，阿比特龙和奥拉帕利组的中位数ibPFS显著长于阿比拉酮和安慰剂组(24.8个月比16.6个月；风险比0.66；95%可信区间[CI]，0.54至0.81；P
BACKGROUND: Preclinical studies and results of a phase 2 trial of abiraterone and olaparib suggest a combined antitumor effect when the poly(adenosine diphosphate[ADP]-ribose) polymerase inhibitor olaparib is combined with next-generation hormonal agent abiraterone to treat metastatic castration-resistant prostate cancer (mCRPC). METHODS: We conducted a double-blind, phase 3 trial of abiraterone and olaparib versus abiraterone and placebo in patients with mCRPC in the first-line setting. Patients were enrolled regardless of homologous recombination repair gene mutation (HRRm) status. HRRm status was determined following enrollment by tumor tissue and circulating tumor DNA tests. Patients were randomly assigned (1:1) to receive abiraterone (1000mg once daily) plus prednisone or prednisolone with either olaparib (300mg twice daily) or placebo. The primary end point was imaging-based progression-free survival (ibPFS) by investigator assessment. Overall survival was among the secondary end points. RESULTS: At this planned primary analysis at the first data cutoff, median ibPFS was significantly longer in the abiraterone and olaparib arm than in the abiraterone and placebo arm (24.8 vs. 16.6 months; hazard ratio, 0.66; 95% confidence interval [CI], 0.54 to 0.81; P