Correlation of Prostate-specific Antigen Kinetics with Overall Survival and Radiological Progression-free Survival in Metastatic Castration-sensitive Prostate Cancer Treated with Abiraterone Acetate plus Prednisone or Placebos Added to Androgen Deprivation Therapy: Post Hoc Analysis of Phase 3 LATITUDE Study.
前列腺特异性抗原动力学与转移性去势敏感前列腺癌总生存率和放射无进展生存率的相关性: 醋酸阿比特龙加强的松或安慰剂加入雄激素剥夺疗法治疗: 第三阶段纬度研究的事后分析。
Abiraterone Metastatic castration-sensitive prostate cancer Overall survival Prostate-specific antigen kinetics Radiological progression-free survival
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摘要

BACKGROUND:LATITUDE, a randomized, double-blind trial, compared abiraterone acetate and prednisone (AAP) + androgen deprivation therapy (ADT) versus placebo (PBO) + ADT in high-risk metastatic castration-sensitive prostate cancer (mCSPC).
OBJECTIVE:To assess the correlation of prostate-specific antigen (PSA) kinetics with overall survival (OS) and radiological progression-free survival (rPFS).
DESIGN, SETTING, AND PARTICIPANTS:A post hoc analysis of data from 597 men receiving AAP + ADT and 602 receiving PBO + ADT.
OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS:The associations of PSA-related outcomes (rates of confirmed 50% [PSA50] and 90% [PSA90] decline from baseline PSA [Prostate Cancer Working Group 2 criteria], rates of PSA < 0.2 ng/ml, median nadir PSA, time to PSA nadir [TPN], and time to PSA progression [TPP] with long-term outcomes [OS and rPFS]) were evaluated. Hazard ratios (HRs) were estimated using Cox proportional hazard model. Correlations of TPP with coprimary endpoints rPFS and OS were evaluated using Kendall's tau (KT).
RESULTS AND LIMITATIONS:AAP + ADT significantly delayed median TPP versus PBO + ADT (33.2 vs 7.4 mo; HR: 0.3, p <  0.001). TPP correlated with rPFS (KT = 0.921) and OS (KT = 0.666). In the AAP + ADT group, 91% had PSA50 and 79% had PSA90 responses (relative risk [RR]: 1.36 and 2.30, respectively; p <  0.001 for both comparisons vs PBO + ADT). Compared with nonresponders, PSA50 and PSA90 responders had reduced risk of death (RR: 0.44 and 0.12, respectively). At 6 mo, 40% receiving AAP + ADT and 6.5% receiving PBO + ADT achieved PSA ≤0.1 ng/ml, which was significantly associated with longer rPFS and OS. Median nadir PSA was 0.09 ng/ml with AAP + ADT versus 2.36 ng/ml with PBO + ADT. Median TPN (AAP + ADT, 6.4 mo; PBO + ADT, 3.8 mo) positively correlated with rPFS and OS.
CONCLUSIONS:Superior PSA response dynamics with AAP + ADT versus ADT + PBO strongly correlated with long-term outcomes of rPFS and OS in high-risk mCSPC.
PATIENT SUMMARY:We found that low prostate-specific antigen levels (≤0.1 ng/ml) after 6 mo may indicate a good long-term response to treatment. Our results need confirmation.

译文

背景: LATITUDE 是一项随机、双盲试验,比较了醋酸阿比特龙和泼尼松 (AAP) 雄激素剥夺疗法 (ADT) 与安慰剂 (PBO) ADT 治疗高危转移性去势敏感前列腺癌 (mCSPC)。
目的: 评估前列腺特异性抗原 (PSA) 动力学与总生存期 (OS) 和放射学无进展生存期 (rPFS) 的相关性。
设计、设置和参与者: 对 597 名接受 aap  adadt 的男性和 602 名接受 PBO  adadt 的男性数据的事后分析。
结果测量和统计分析: PSA 相关结果的关联 (50% [PSA50] 和 90% [PSA90] 的确认率从基线 PSA [前列腺癌工作组 2 标准] 下降, PSA 的比率 <0.2 纳克/毫升,PSA 中位数最低点,PSA 最低点 [TPN] 的时间,以及 PSA 进展的时间 [TPP]评估长期结果 [OS 和 rPFS])。使用 Cox 比例风险模型估计风险比 (HRs)。使用 Kendall's tau (KT) 评估 TPP 与互质终点 rPFS 和 OS 的相关性。
结果和局限性: aap adadadt 显著延迟了中位数 TPP 与 pboadadadt (33.2 vs 7.4 mo; HR: 0.3,p <0.001)。TPP 与 rPFS (KT = 0.921) 和 OS (KT = 0.666) 相关。在 AAP ADT 组中,91% 的人有 PSA50,79% 的人有 PSA90 反应 (相对风险 [RR]: 分别为 1.36 和 2.30; 与 PBO ADT 相比,两次比较的 p <-0.001)。与无反应者相比,PSA50 和 PSA90 反应者的死亡风险降低 (RR: 分别为 0.44 和 0.12)。在 6 个月时,40% 接受 AAP ADT,6.5% 接受 PBO ADT,达到 PSA ≤ 0.1 ng/ml,这与较长的 rPFS 和 OS 显著相关。AAP ADT 的平均最低 PSA 为 0.09 ng/ml,而 PBO ADT 为 2.36 ng/ml。中位 TPN (AAP ADT,6.4 mo; PBO ADT,3.8 mo) 与 rPFS 和 OS 呈正相关。
结论: aap   adadt 与 adt   pbo 的卓越 PSA 反应动态与高危 mCSPC 的 rPFS 和 OS 的长期结果密切相关。
患者总结: 我们发现 6 个月后前列腺特异性抗原水平低 (≤ 0.1 纳克/毫升) 可能表明对治疗有良好的长期反应。我们的结果需要确认。

Abiraterone

肿瘤 前列腺癌 药物
概述  :  

阿比特龙是一种白色至淡白色的化学物质;化学名称叫做:17-(3-吡啶基)雄甾-5,16-二烯-3β-醇,分子式为:C24H31NO;其分子量为:349.51。阿比特龙是CYP17A1(17α-羟化酶/C17,20-裂解酶)的一种有效抑制剂,无细胞试验中IC50为2 nm,可用于治疗前列腺癌症,目前已有上市产品。阿比特龙专利药是由美国Couger Biotechnology(现已被强生收购)研发,于2011年由美国FDA批准上市,目前已进入中国市场,该药商品名为Zytiga

Abiraterone
释    义   阿比特龙
例    句   Phase III trial of abiraterone is planned for next year.   阿比特龙的III期试验计划在明年进行。

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