Department of Geriatrics, Peking University First Hospital, Beijing, People's Republic of China.
Department of Pharmacy, Peking University First Hospital, Beijing, People's Republic of China.
Cancer Med. 2023 Apr;12(8):9272-9281. doi: 10.1002/cam4.5669. Epub 2023 Feb 2.
The programmed cell death protein 1 (PD-1) inhibitor, as one of the immune checkpoint inhibitors (ICIs), is the standard treatment for advanced lung cancer. However, immune-related adverse events (irAEs) remain poorly understood toxicities. It is unclear whether frailty plays a role in the occurrence of irAEs. Thus, we assess whether irAEs occur more often in frail patients than in non-frail patients according to the Frailty Index (FI).
A retrospective study was conducted. Medical records from lung cancer patients treated with PD-1 inhibitors (Sintilimab, Camrelizumab, Tislelizumab, and Pembrolizumab) at Peking University First Hospital (May 2018-June 2022). Patients were categorized into non-frail and frail groups according to a cut-point of 0.25 by FI. The FI calculation included 28 baseline variables, all of which were health deficits measured by questionnaires and body measurements.
The statistical analysis included 114 advanced lung cancer patients. The median age was 66 years, and the male/female ratio was 4.7:1 (94/20). Approximately 39 (34%) were classified as frail. PD-1 inhibitor-related adverse events occurred in 17.5% of patients, and 6.1% experienced irAEs of grade ≥3. There was no significant difference in the occurrence of irAEs (14.7% vs. 23.1%, p = 0.26), grade ≥ 3 irAEs (5.3% vs. 7.7%, p = 0.93), and treatment discontinuation due to irAEs (12.0% vs. 17.9%, p = 0.39) between non-frail and frail patients. However, frail patients are more likely to have more than one type of irAEs and are more possibly to have checkpoint inhibitor pneumonitis (CIP) than non-frail patients when they use PD-1 inhibitors (p < 0.05). Frail patients had a longer hospital stay (6 vs. 3 days, p = 0.01).
Frailty is not associated with severe irAEs, but is related to CIP. Meanwhile, it predicts more than one type of irAEs and a longer hospital stay. Frailty screening has added value to the decision-making process for frail patients eligible for PD-1 inhibitors.
程序性细胞死亡蛋白 1（PD-1）抑制剂作为免疫检查点抑制剂（ICI）之一，是晚期肺癌的标准治疗方法。然而，免疫相关不良事件（irAEs）仍然是了解甚少的毒性。目前尚不清楚脆弱是否与 irAEs 的发生有关。因此，我们根据脆弱指数（FI）评估脆弱患者与非脆弱患者相比，irAEs 是否更常见。
进行了一项回顾性研究。北京大学第一医院（2018 年 5 月至 2022 年 6 月）接受 PD-1 抑制剂（信迪利单抗、卡瑞利珠单抗、替雷利珠单抗和帕博利珠单抗）治疗的肺癌患者的病历。根据 FI 的 0.25 截断值，患者分为非脆弱组和脆弱组。FI 的计算包括 28 个基线变量，均为通过问卷调查和身体测量得出的健康缺陷。
统计分析包括 114 例晚期肺癌患者。中位年龄为 66 岁，男女比例为 4.7:1（94/20）。约 39 例（34%）被归类为脆弱。PD-1 抑制剂相关不良事件发生率为 17.5%，≥3 级 irAEs 发生率为 6.1%。非脆弱组和脆弱组的 irAEs 发生率（14.7% vs. 23.1%，p=0.26）、≥3 级 irAEs 发生率（5.3% vs. 7.7%，p=0.93）和因 irAEs 而停止治疗的发生率（12.0% vs. 17.9%，p=0.39）无显著差异。然而，与非脆弱患者相比，脆弱患者更有可能出现一种以上的 irAEs，并且在使用 PD-1 抑制剂时更有可能发生检查点抑制剂性肺炎（CIP）（p<0.05）。脆弱患者的住院时间更长（6 天 vs. 3 天，p=0.01）。
脆弱与严重 irAEs 无关，但与 CIP 有关。同时，它预测了一种以上的 irAEs 和更长的住院时间。脆弱筛查为适合使用 PD-1 抑制剂的脆弱患者的决策过程增加了价值。
