Department of Internal Medicine, National Cancer Center, Goyang, Korea.
Department of Radiology, National Cancer Center, Goyang, Korea.
Cancer Res Treat. 2021 Jan;53(1):77-86. doi: 10.4143/crt.2020.543. Epub 2020 Aug 6.
Immune checkpoint inhibitors (ICI) and targeted small-molecule drugs are mainstay elements of lung cancer chemotherapy. However, they are associated with development of pneumonitis, a rare, but potentially life-threatening event. We analyzed lung cancer patients treated with ICI to evaluate the effect of sequential therapeutic administration on the incidence of pneumonitis.
In this retrospective study, 242 patients were included. Serial radiologic findings taken during and immediately after ICI treatment were reviewed. Factors that increased pneumonitis and the relationship between peri-ICI chemotherapy and the development of pneumonitis were evaluated.
Pneumonitis developed in 23 patients (9.5%); severe pneumonitis (grade ≥ 3) occurred in 13 of 23 patients (56%); pneumonitis-related death occurred in six. High-dose thoracic radiation (≥ 6,000 cGy) revealed a tendency toward high risk of pneumonitis (odds ratio, 2.642; 95% confidence interval, 0.932 to 7.490; p=0.068). Among 149 patients followed for ≥ 8 weeks after the final ICI dose, more patients who received targeted agents within 8-weeks post-ICI experienced pneumonitis (3/16, 18.8%) compared with patients who received cytotoxic agents (4/54, 7.4%) or no chemotherapy (4/79, 5.1%) (p=0.162). Targeted therapy was associated with earlier-onset pneumonitis than treatment with cytotoxic agents (35 vs. 62 days post-ICI, p=0.007); the resulting pneumonitis was more severe (grade ≥ 3, 100% vs. 0%, p=0.031).
Sequential administration of small-molecule targeted agents immediately after ICI may increase the risk of severe pneumonitis. The sequence of chemotherapy regimens that include ICI and targeted agents should be carefully planned to reduce the risk of pneumonitis in lung cancer patients.
免疫检查点抑制剂（ICI）和靶向小分子药物是肺癌化疗的主要组成部分。然而，它们与肺炎的发生有关，肺炎是一种罕见但潜在危及生命的事件。我们分析了接受 ICI 治疗的肺癌患者，以评估序贯治疗对肺炎发生率的影响。
在这项回顾性研究中，纳入了 242 名患者。回顾了 ICI 治疗期间和治疗后立即进行的连续影像学检查结果。评估了增加肺炎的因素以及 ICI 围化疗与肺炎发生之间的关系。
23 名患者（9.5%）发生了肺炎；23 名患者中有 13 名（56%）发生了严重肺炎（≥3 级）；6 名患者因肺炎相关死亡。高剂量胸部放疗（≥6000cGy）显示出发生肺炎的高风险倾向（比值比，2.642；95%置信区间，0.932 至 7.490；p=0.068）。在最后一次 ICI 剂量后≥8 周随访的 149 名患者中，与接受细胞毒性药物（4/54，7.4%）或无化疗（4/79，5.1%）的患者相比，在 ICI 后 8 周内接受靶向药物的患者发生肺炎的比例更高（3/16，18.8%）（p=0.162）。靶向治疗与细胞毒性药物相比，肺炎的发病更早（ICI 后 35 天 vs. 62 天，p=0.007）；导致的肺炎更严重（≥3 级，100% vs. 0%，p=0.031）。
ICI 后立即序贯给予小分子靶向药物可能会增加严重肺炎的风险。在包含 ICI 和靶向药物的化疗方案中，应仔细规划方案顺序，以降低肺癌患者肺炎的风险。
