晚期 NSCLC 患者存在致癌驱动基因改变时，接受免疫检查点抑制剂治疗后使用酪氨酸激酶抑制剂治疗引起严重不良事件的发生率。
Incidence of serious adverse events caused by tyrosine kinase inhibitor treatment following immune checkpoint inhibitor therapy in advanced NSCLC patients with oncogenic driver alterations.
机构信息
Department of Thoracic Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-Ku, Tokyo, 104-0045, Japan.
Department of Experimental Therapeutics, National Cancer Center Hospital, 5-1-1, Tsukiji, Chuo-Ku, Tokyo, 104-0045, Japan.
出版信息
Cancer Immunol Immunother. 2023 Aug;72(8):2613-2621. doi: 10.1007/s00262-023-03429-z. Epub 2023 Apr 16.
BACKGROUND
Sequential tyrosine kinase inhibitors (TKIs) following immune checkpoint inhibitors (ICIs) increases the incidence of serious adverse events (SAEs). However, the factors and the types of TKIs that affect the incidence of SAEs remain unknown.
METHODS
We retrospectively reviewed advanced non-small cell lung cancer (NSCLC) patients who received sequential TKIs following ICIs between November 2015 and April 2021. All AEs were evaluated using Common Terminology Criteria for Adverse Events (CTCAE) ver 5.0.
RESULTS
Among 1,638 NSCLC patients who received ICIs, 63 patients received sequential TKIs following ICIs. The types of TKIs included EGFR-TKIs in 48 patients, ALK-TKIs in 10 patients, and others in 5 patients. The median dosing interval was 57 days (range: 7-698). Eighteen (28.6%) patients developed SAEs (Grade 3/4 or hospitalized). The incidence of SAEs and withdrawal of TKIs due to AEs were significantly higher in patients (n = 40) who initiated TKI treatment within 3 months after ICIs than in patients (n = 23) who initiated TKI treatment 3 months after ICIs (SAEs, 40.0% vs. 4.3%, p < 0.01; withdrawal rate: 57.5% vs. 21.7%, p < 0.01). There was no significant difference in the incidence of SAEs and withdrawal rate due to AEs between EGFR-TKIs and other TKIs (SAE, 22.9% vs. 40.0%, p = 0.20; withdrawal rate: 41.7% vs. 53.3%, p = 0.55).
CONCLUSION
The dosing interval from last ICI to the initiation of TKI treatment can affects the incidence of SAEs and the withdrawal rate due to AEs regardless of the types of TKIs.
背景
免疫检查点抑制剂（ICI）序贯酪氨酸激酶抑制剂（TKI）会增加严重不良事件（SAE）的发生率。然而，影响 SAE 发生率的因素和 TKI 类型仍不清楚。
方法
我们回顾性分析了 2015 年 11 月至 2021 年 4 月间接受 ICI 序贯 TKI 治疗的晚期非小细胞肺癌（NSCLC）患者。所有不良事件均采用不良事件通用术语标准（CTCAE）第 5.0 版进行评估。
结果
在接受 ICI 治疗的 1638 例 NSCLC 患者中，有 63 例患者接受了 ICI 序贯 TKI 治疗。TKI 的类型包括 48 例患者的 EGFR-TKI、10 例患者的 ALK-TKI 和 5 例患者的其他 TKI。中位给药间隔为 57 天（范围：7-698 天）。18 例（28.6%）患者发生 SAE（3/4 级或住院）。ICI 后 3 个月内开始 TKI 治疗（n=40）的患者与 ICI 后 3 个月开始 TKI 治疗（n=23）的患者相比，SAE 的发生率和因不良事件而停用 TKI 的发生率均显著更高（SAE：40.0%比 4.3%，p<0.01；停药率：57.5%比 21.7%，p<0.01）。EGFR-TKI 和其他 TKI 之间 SAE 的发生率和因不良事件而停药率无显著差异（SAE：22.9%比 40.0%，p=0.20；停药率：41.7%比 53.3%，p=0.55）。
结论
末次 ICI 至开始 TKI 治疗的给药间隔时间可能会影响 SAE 的发生率和因不良事件而停药率，而与 TKI 的类型无关。
Zotero 插件