Department of Clinical Pharmacy and Toxicology, Leiden University Medical Centre, Leiden, The Netherlands.
Department of Pharmacy, Haga Teaching Hospital, The Hague, The Netherlands.
BMC Cancer. 2023 Mar 14;23(1):247. doi: 10.1186/s12885-023-10701-z.
This study was designed to investigate the impact of age on the effectiveness and immune-related adverse events (irAEs) of programmed death-(ligand)1 [PD-(L)1] inhibitors in patients with non-small cell lung cancer (NSCLC) using a novel text-mining technique.
This retrospective study included patients with stage III/IV NSCLC treated with a PD-(L)1 inhibitor (nivolumab, pembrolizumab, atezolizumab and durvalumab) at Leiden University Medical Centre and Haga Teaching hospital, (both in The Netherlands) from September 2016 to May 2021. All the relevant data was extracted from the structured and unstructured fields of the Electronic Health Records using a novel text-mining tool. Effectiveness [progression-free survival (PFS) and overall survival (OS)] and safety (the incidence of nine potentially fatal irAEs and systemic corticosteroid requirement) outcomes were compared across age subgroups (young: < 65 years, Middle-aged: 65-74 years, and old: ≥ 75 years) after adjustment for confounding.
Of 689 patients, 310 patients (45.0%) were < 65 years, 275 patients (39.9%) were aged between 65 and 74 years, and 104 patients (15.1%) were ≥ 75 years. There was no significant difference between younger and older patients regarding PFS (median PFS 12, 8, 13 months respectively; Hazard ratio (HR) = 1.14, 95% CI 0.92-1.41; HR = 1.10, 95% CI 0.78-1.42). This was also the case for OS (median OS 19, 14, 18 months respectively; HR = 1.22, 95% CI 0.96-1.53; HR = 1.10, 95% CI 0.79-1.52). Safety analysis demonstrated a higher incidence of pneumonitis among patients aged 65-74. When all the investigated irAEs were pooled, there was no statistically significant difference found between age and the incidence of potentially fatal irAEs.
The use of PD-(L)1 inhibitors is not associated with age related decrease of PFS and OS, nor with increased incidence of serious irAEs compared to younger patients receiving these treatments. Chronological age must therefore not be used as a predictor for the effectiveness or safety of ICIs.
本研究旨在使用一种新的文本挖掘技术，探讨年龄对非小细胞肺癌（NSCLC）患者程序性死亡配体 1（PD-（L）1）抑制剂疗效和免疫相关不良事件（irAE）的影响。
本回顾性研究纳入了 2016 年 9 月至 2021 年 5 月在莱顿大学医学中心和哈格教学医院（均位于荷兰）接受 PD-（L）1 抑制剂（nivolumab、pembrolizumab、atezolizumab 和 durvalumab）治疗的 III/IV 期 NSCLC 患者。所有相关数据均使用一种新的文本挖掘工具从电子健康记录的结构化和非结构化字段中提取。在调整混杂因素后，比较了不同年龄亚组（年轻：<65 岁，中年：65-74 岁，老年：≥75 岁）之间的疗效（无进展生存期（PFS）和总生存期（OS））和安全性（9 种潜在致命 irAE 和全身皮质类固醇需求的发生率）结局。
在 689 名患者中，310 名（45.0%）患者<65 岁，275 名（39.9%）患者年龄在 65-74 岁之间，104 名（15.1%）患者≥75 岁。年轻患者和老年患者的 PFS 无显著差异（中位 PFS 分别为 12、8、13 个月；风险比（HR）=1.14，95%CI 0.92-1.41；HR=1.10，95%CI 0.78-1.42）。OS 也是如此（中位 OS 分别为 19、14、18 个月；HR=1.22，95%CI 0.96-1.53；HR=1.10，95%CI 0.79-1.52）。安全性分析表明，65-74 岁患者的肺炎发生率较高。当所有研究的 irAE 被汇总时，年龄与潜在致命 irAE 的发生率之间没有统计学意义上的差异。
与年轻患者接受这些治疗相比，使用 PD-（L）1 抑制剂不会导致与年龄相关的 PFS 和 OS 下降，也不会导致严重 irAE 的发生率增加。因此，年龄不应作为预测 ICIs 疗效或安全性的指标。
