Smith Katherine E R, Pritzl Stephanie L, Yu Wei, Bara Ilze, Thanarajasingam Gita, Kaul Monika D, Williams Kirstin A, Dueck Amylou C, Mansfield Aaron S
Department of Oncology, Mayo Clinic, Rochester, Minnesota.
Genentech Inc., South San Francisco, California.
JTO Clin Res Rep. 2023 Nov 23;4(12):100611. doi: 10.1016/j.jtocrr.2023.100611. eCollection 2023 Dec.
Immune-related adverse events (irAEs) due to immune checkpoint inhibitors can have complicated clinical courses. We comprehensively evaluated the timing, trajectory, and incidence of both single and multiple irAEs for NSCLC treated with atezolizumab.
Data were pooled from 2457 patients who participated in the IMpower130, IMpower132, and IMpower150 clinical trials investigating the use of atezolizumab in metastatic NSCLC as part of a chemoimmunotherapy regimen. Longitudinal irAE data with landmark analysis, time-to-onset, changes in grading severity, and occurrence of multiple events were summarized.
In general, 1557 patients were treated with atezolizumab and 900 patients were in the control groups. Median follow-up was 32.3 and 23.5 months, respectively. In the atezolizumab group, 753 patients (48.4%) experienced at least one irAE. In the control group, 289 patients (32.1%) experienced at least one nonimmune adverse event that was attributed to an irAE. In the atezolizumab group, the most common irAEs were rash, hepatitis, and hypothyroidism. Furthermore, 13% of the patients experienced two irAEs and 4% experienced three irAEs. Within 5 months of treatment, the cumulative incidence for any irAE was 39.2%. Median time-to-onset varied from 1 to 10 months based on the specific irAE. Grade 1 to 2 irAEs increased in severity for 33% of the patients.
We identified dynamic clinical patterns for irAEs in patients treated with atezolizumab, including variations in time-to-onset, incidence of multiple irAEs, and frequency of irAEs increasing in severity. These results can guide clinical management and future reporting of adverse events to enable comprehensive longitudinal analyses.
免疫检查点抑制剂引起的免疫相关不良事件（irAE）临床过程可能较为复杂。我们全面评估了接受阿替利珠单抗治疗的非小细胞肺癌（NSCLC）患者发生单发性和多发性irAE的时间、发展轨迹及发生率。
数据来自2457例参与IMpower130、IMpower132和IMpower150临床试验的患者，这些试验研究了阿替利珠单抗作为化疗免疫治疗方案的一部分用于转移性NSCLC的情况。汇总了具有标志性分析的纵向irAE数据、发病时间、分级严重程度变化以及多事件发生情况。
总体而言，1557例患者接受了阿替利珠单抗治疗，900例患者在对照组。中位随访时间分别为32.3个月和23.5个月。在阿替利珠单抗组中，753例患者（48.4%）发生了至少一次irAE。在对照组中，289例患者（32.1%）发生了至少一次归因于irAE的非免疫不良事件。在阿替利珠单抗组中，最常见的irAE是皮疹、肝炎和甲状腺功能减退。此外，13%的患者发生了两次irAE，4%的患者发生了三次irAE。在治疗的5个月内，任何irAE的累积发生率为39.2%。根据具体的irAE，中位发病时间从1个月到10个月不等。33%的患者1至2级irAE严重程度增加。
我们确定了接受阿替利珠单抗治疗患者irAE的动态临床模式，包括发病时间的变化、多发性irAE的发生率以及irAE严重程度增加的频率。这些结果可指导临床管理以及未来不良事件的报告，以实现全面的纵向分析。
