研究发现骨转移药物可延长转移性去势难治性前列腺癌患者生存期

一项随机三期多国试验显示一种新的放射源物质现在用于靶向治疗，在患有转移性去势疗法（激素）耐受的前列腺肿瘤（CRPC）中靶向治疗骨转移。这一物质可以同时提高生存时间和延缓肿瘤相关的骨疾病。这种物质，氯化镭-223（Ra-223），是第一种阿尔法粒子辐射药物，对于转移的CPRC患者，可以靶向治疗其骨骼，提高生存时间。

“就在2年前，我们对于患有这种进展性前列腺肿瘤的患者，只有非常少的几种治疗选择，”首席作者A. Oliver Sartor这样说道。他是位于新奥尔良的杜兰大学医学院肿瘤研究中心的著名教授和杜兰肿瘤中心的医学主任。“现在我们有很多方法，但是镭-223是第一种降低骨骼相关事件（SREs)改善生产事件的，使得这成为一种独一无二的有前途的治疗选择。

睾酮水平很低时肿瘤持续增长，认为是前列腺肿瘤对去势疗法无效。镭-223是一种新的物质可以直接对骨肿瘤作用，通过短时间爆发的高能阿尔法辐射起到治疗左右。在这项成为ALSYMPCA的试验中，Sartor和他的同事对922名肿瘤进展的患者进行随机试验。

合并骨转移的CPRC患者随机接受镭-223加上最好的支持治疗或者接受安慰剂加最好的护理治疗。805名患者的中期分析显示镭-223和安慰剂相比，显著的增加了中位生存时间（14.0个月比11.2个月）。结果是，这一试验提前结束，还要提到的是，这是第一次临床试验发现SRE显著延迟（发生SRE的中位时间是13.6个月比安慰剂组的8.4个月）

最好的支持治疗包括对其肿瘤症状的治疗的评估，而不仅是对疾病预后的改善；其包括抗生素，止痛药，对于骨转移的放射止痛治疗和皮质醇激素的应用。SREs 包括骨折，脊柱压缩，体外射线治疗和骨科手术。

“这些发现将有助于我们增加个体化的进展期前列腺肿瘤治疗。用一种新的药物来延长患者的生命。”Sartor说道。他说道，下一步的研究将计划检测镭-223和其他药物合用的有效性。研究需要确定镭-223是否和最新的免疫治疗，激素治疗和化疗药物合用有效。还有其他研究者已经开始测试镭-223在乳腺癌骨转移患者中的作用，并且计划进行镭-223在其他肿瘤的临床研究。

摘要号：LBA4512

题目：Updated analysis of the phase III, double-blind, randomized, multinational study of radium-223 chloride in castration-resistant prostate cancer (CRPC) patients with bone metastases (ALSYMPCA).

镭-223氯化物治疗去势难治性前列腺癌(CRPC)骨转移患者的随机双盲多中心III期研究(ALSYMPCA)最新分析结果

摘要：

Background: Radium-223 chloride (Ra-223), a targeted alpha-emitter, targets bone metastases (mets) with high-energy alpha-particles of short range (<100 ??m). ALSYMPCA, a phase III double-blind, randomized, multinational study, compared Ra-223 plus best standard of care (BSC) vs placebo plus BSC in CRPC patients (pts) with bone mets. In a planned interim analysis (n = 809), based on 314 events, Ra-223 significantly improved overall survival (OS) vs placebo (median 14.0 mo vs 11.2 mo, respectively; HR = .695; 95% CI, .552-.875; 2-sided p = .00185). Secondary endpoints were met and Ra-223 safety was favorable. An updated analysis was conducted prior to the crossover to further assess the effect of Ra-223 on the primary endpoint (OS), secondary endpoints including skeletal-related events (SREs), and safety.

Methods: Eligible pts had confirmed symptomatic CRPC with ≥ 2 bone mets; no known visceral mets; and were post-docetaxel, unfit for docetaxel, or had declined docetaxel. Pts were randomized 2:1 to receive 6 injections of Ra-223 (50 kBq/kg IV) q4wks or matching placebo. An updated descriptive analysis of OS, based on 528 events, was performed including data from all randomized pts prior to implementing crossover to Ra-223 for placebo pts.

Results: 921 pts (Ra-223, n = 614; placebo, n = 307) were randomized from 6/2008-2/2011. Ra??223 significantly improved OS vs placebo (median 14.9 mo vs 11.3 mo, respectively; HR = .695; 95% CI, .581-.832; p = 0.00007), and time to first SRE was significantly prolonged (median 15.6 mo vs 9.8 mo, respectively; HR = 0.658; 95% CI, 0.522-0.830; p = 0.00037). Safety and tolerability of Ra-223 remained favorable, with low myelosuppression (e.g., gr 3/4 neutropenia in 2.2% and 0.7% and gr 3/4 thrombocytopenia in 6.3% and 2% of the Ra-223 and placebo groups, respectively).

Conclusions: On updated analysis, the median OS benefit for Ra-223 increased from 2.8 to 3.6 months, with a hazard ratio of 0.695 (i.e., 30.5% reduction in risk of death). Ra-223 is an effective therapy that improves OS and time to first SRE with a highly favorable safety profile, and may provide a new standard of care for CRPC pts with bone mets.

编辑: xy 作者:丁香园通讯员

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