Clin Cancer Res:早早使用大剂量激素管理irAE与抗PD-1单药治疗晚期黑色素瘤的预后不良相关

2021-08-12 Nebula MedSci原创

早早使用大剂量激素管理irAE与抗PD-1单药治疗晚期黑色素瘤的预后不良相关

程序性细胞死亡受体-1 (PD-1)抑制剂是晚期黑色素瘤的一线治疗方法。严重的免疫相关不良反应(ieAE)通常需要糖皮质激素(GCC)免疫抑制治疗。但是,在抗PD-1单药治疗过程中,GCC的使用及其与患者生存预后的相关性尚未明确。

这是一项多中心的回顾性分析,纳入了2009年至2019年期间采用抗PD-1单克隆疗法治疗的患者,从5个独立的队列中采集详细的GCC使用数据。中位随访时间为206周。从抗PD-1治疗开始跟踪irAE,直到病情进展、开始新的治疗或随后一次随访。最后还分析了irAE、GCC使用和存活预后的相关性。

MGH队列和验证队列两组患者的PFS

在总队列947位患者中,509位(54%)患者发生了irAE。在MGH队列(irAE[+]n=90)中,与未早期使用大剂量GCC的irAE相比,使用了大剂量GCC(≥60 mg,强的松)的早发型irAE(抗PD-1治疗后的前8周内)与irAE后的PFS和OS较差独立相关 (irAE后 PFS: HR 5.37, 95%CI 2.10-13.70, p<0.001; OS: HR 5.95, 95%CI 2.20-16.09, p<0.001)。

MGH队列和验证队列两组患者的OS

上述研究结果在联合验证队列中得到了证实(irAE[+]n=419, irAE后 PFS: HR1.69, 95%CI 1.04-2.76, p=0.04; OS: HR 1.97, 95%CI 1.15-3.39, p=0.01)。此外,在irAE后PFS的26周重要分析中,观察到了相似的结果,但在irAE后OS的26周分析中未观察到相似的结果。采用累积GCC暴露量为测量的敏感性分析也获得了相似的结果。

综上,irAE发生后,早早使用大剂量GCC与不良PFS和OS预后相关。在抗PD-1单药治疗过程中,应更理智的应用GCC。需要开展前瞻性的随机对照临床试验进一步验证该研究结果。

原始出处:

Xue Bai, Jiani Hu, Allison Betof Warner, et al. Early use of high-dose-glucocorticoid for the management of irAE is associated with poorer survival in patients with advanced melanoma treated with anti-PD-1 monotherapy. Clin Cancer Res August 10 2021 DOI:10.1158/1078-0432.CCR-21-1283

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    2021-12-21 sunylz
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    2021-08-13 学医无涯

    每日一看~

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