Department of Internal Medicine, University of California Davis Comprehensive Cancer Center, Sacramento, California, USA
EMD Serono Research & Development Institute, Inc, Billerica, Massachusetts, USA; an affiliate of Merck KGaA, Darmstadt, Germany.
J Immunother Cancer. 2020 Nov;8(2). doi: 10.1136/jitc-2020-001427.
Adverse events (AEs) of special interest that arise during treatment with immune checkpoint inhibitors, including immune-related AEs (irAEs), have been reported to be associated with improved clinical outcomes. We analyzed patients treated with avelumab from the JAVELIN Solid Tumor and Merkel 200 trials, examining the association between AEs and efficacy while adjusting for confounding factors such as treatment duration and event order.
We analyzed efficacy and safety data from 1783 patients treated with the programmed death ligand 1 inhibitor avelumab who were enrolled in expansion cohorts of the JAVELIN Solid Tumor and Merkel 200 trials. To analyze the association between irAEs and efficacy with regard to survival, we used a time-dependent Cox model with time-varying indicators for irAEs, as well as multistate models that accounted for competing risks and time inhomogeneity.
295 patients (16.5%) experienced irAEs and 454 patients (25.5%) experienced infusion-related reactions. There was a reduced risk of death in patients who experienced irAEs compared with those who did not (HR 0.71, 95% CI 0.59 to 0.85) using the time-dependent Cox model. The multistate model did not suggest that the occurrence of irAEs could predict response; however, it predicted a higher chance of irAEs occurring after a response. No association was observed between response and infusion-related reactions.
Patients who experience irAEs showed improved survival. Although irAEs are not predictors for response to immune checkpoint inhibitors, increased vigilance for irAEs is needed after treatment with avelumab.
NCT01772004 and NCT02155647.
免疫检查点抑制剂治疗期间出现的特殊关注的不良事件（AE），包括免疫相关不良事件（irAE），已被报道与改善的临床结局相关。我们分析了 JAVELIN 实体瘤和 Merkel 200 试验中接受avelumab 治疗的患者，考察了 AE 与疗效之间的关联，同时调整了治疗持续时间和事件顺序等混杂因素。
我们分析了 1783 例接受程序性死亡配体 1 抑制剂avelumab 治疗的患者的疗效和安全性数据，这些患者来自 JAVELIN 实体瘤和 Merkel 200 试验的扩展队列。为了分析 irAE 与生存相关的疗效关联，我们使用了一个时间依赖性 Cox 模型，该模型具有 irAE 的时变指标，以及多状态模型，这些模型考虑了竞争风险和时间异质性。
295 例（16.5%）患者发生 irAE，454 例（25.5%）患者发生输注相关反应。与未发生 irAE 的患者相比，发生 irAE 的患者死亡风险降低（HR 0.71，95%CI 0.59 至 0.85），使用时间依赖性 Cox 模型。多状态模型表明，irAE 的发生不能预测反应；然而，它预测了在发生反应后发生 irAE 的可能性更高。反应与输注相关反应之间没有关联。
发生 irAE 的患者显示出生存改善。尽管 irAE 不是免疫检查点抑制剂反应的预测因素，但在使用avelumab 治疗后，需要对 irAE 保持更高的警惕。
NCT01772004 和 NCT02155647。
