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阿特珠单抗联合恩杂鲁胺与单独恩杂鲁胺治疗转移性去势抵抗型前列腺癌的3期临床试验
2022-01-12 13:48
来源：小柯机器人

美国丹娜·法伯癌症研究所Christopher J. Sweeney、英国伦敦玛丽女王大学Thomas Powles等研究人员，合作完成阿特珠单抗联合恩杂鲁胺与单独恩杂鲁胺治疗转移性去势抵抗型前列腺癌的3期临床试验。相关论文于2022年1月10日在线发表于国际学术期刊《自然—医学》。

研究人员在IMbassador250试验（编号：NCT03016312）中招募了759名患有转移性去势抵抗前列腺癌的男性，他们的疾病在使用阿比特龙后出现进展。在一项开放标签的随机试验中，将阿特珠单抗加入恩扎鲁胺中，尽管安全性可以接受，但未达到改善未选择患者总生存期的主要终点（分层危险比1.12，95%置信区间（0.91，1.37），P=0.28）。在存档的肿瘤样本中，前列腺肿瘤显示出相对较低的关键免疫生物标志物的表达。激素敏感型和去势抵抗型前列腺癌之间的DNA损伤反应改变、磷酸酶和tensin同源物状态和PD-L1表达水平相似。
 
在计划的生物标志物分析中，在PD-L1 IC2/3、CD8表达较高和已建立的免疫基因特征的患者中，使用阿特珠单抗的无进展生存期更长。探索性分析将阿特珠单抗治疗组的无进展生存期与免疫基因（如CXCL9和TAP1）以及其他潜在的相关生物标志物（包括磷酸酶和tensin同源物改变）联系起来。这些数据共同表明，与免疫检查点抑制剂反应相关的预期生物学存在于前列腺癌中，尽管患者较少。免疫检查点抑制剂可能需要仔细选择病人，从而确定可能受益于这种治疗方法的病人亚群。
 
据介绍，早期的临床数据表明，一些去势抵抗的前列腺癌患者可能会从PD-L1的抑制中受益，特别是恩扎鲁胺。
 
附：英文原文
 
Title: Atezolizumab with enzalutamide versus enzalutamide alone in metastatic castration-resistant prostate cancer: a randomized phase 3 trial

Author: Powles, Thomas, Yuen, Kobe C., Gillessen, Silke, Kadel, Edward E., Rathkopf, Dana, Matsubara, Nobuaki, Drake, Charles G., Fizazi, Karim, Piulats, Josep M., Wysocki, Piotr J., Buchschacher, Gary L., Alekseev, Boris, Mellado, Begoa, Karaszewska, Bogusawa, Doss, Jennifer F., Rasuo, Grozdana, Datye, Asim, Mariathasan, Sanjeev, Williams, Patrick, Sweeney, Christopher J.

Issue&Volume: 2022-01-10

Abstract: Early clinical data indicate that some patients with castration-resistant prostate cancer may benefit from program death ligand-1 (PD-L1) inhibition, especially with enzalutamide. The IMbassador250 trial (no. NCT03016312) enrolled 759men with metastatic castration-resistant prostate cancer whose disease progressed on abiraterone. The addition of atezolizumab to enzalutamide in an open-label randomized trial did not meet the primary endpoint of improved overall survival in unselected patients (stratified hazard ratio1.12, 95% confidence interval (0.91, 1.37), P=0.28), despite an acceptable safety profile. In archival tumor samples, prostate tumors showed comparatively low expression of key immune biomarkers. DNA damage-response alterations, phosphatase and tensin homolog status and PD-L1 expression levels were similar between hormone-sensitive and castration-resistant prostate cancers. In planned biomarker analysis, longer progression-free survival was seen with atezolizumab in patients with high PD-L1 IC2/3, CD8 expression and established immune gene signatures. Exploratory analysis linked progression-free survival in the atezolizumab arm with immune genes such as CXCL9 and TAP1, together with other potentially relevant biomarkers including phosphatase and tensin homolog alterations. Together these data indicate that the expected biology associated with response to immune checkpoint inhibitors is present in prostate cancer, albeit in fewer patients. Careful patient selection may be required for immune checkpoint inhibitors to identify subgroups of patients who may benefit from this treatment approach.

DOI: 10.1038/s41591-021-01600-6

Source: https://www.nature.com/articles/s41591-021-01600-6

Nature Medicine：《自然—医学》，创刊于1995年。隶属于施普林格·自然出版集团，最新IF：87.241
官方网址：https://www.nature.com/nm/
投稿链接：https://mts-nmed.nature.com/cgi-bin/main.plex


本期文章：《自然—医学》：Online/在线发表

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