Abstract：
BACKGROUND: It is unclear whether the sequential administration of programmed death (PD)-1/programmed death-ligand 1 (PD-L1) inhibitors and epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) is associated with the development of severe interstitial pneumonitis (IP).
METHODS: We identified 69,107 eligible patients with non-small cell lung cancer (NSCLC) from a Japanese national inpatient database, who initiated EGFR-TKI therapy. The study population was divided into the PD-1/PD-L1 inhibitor and non-prior PD-1/PD-L1 groups based on PD-1/PD-L1 administration before EGFR-TKI therapy. We conducted 1:4 matched-pair cohort analyses (n = 9,725) to compare the incidence of IP and in-hospital mortality within 90 days of administration of EGFR-TKI between the two groups after adjusting for the clinical background. Furthermore, we performed subgroup analyses categorized according to the duration of prior PD-1/PD-L1 inhibitor use.
RESULTS: IP occurred in 4.4% of patients in the matched-pair cohort. PD-1/PD-L1 inhibitor-use before EGFR-TKI therapy was significantly associated with IP (odds ratio [OR], 1.79; 95% confidence interval [CI], 1.34-2.38) and in-hospital mortality (OR, 2.10; 95% CI, 1.72-2.55). Prior PD-1/PD-L1 inhibitor use in an interval of <6 months before EGFR-TKI administration was associated with a higher risk of IP than EGFR-TKI administration without prior PD-1/PD-L1 inhibitor. In-hospital mortality was higher in patients with prior PD-1/PD-L1 inhibitor use than that in those without prior PD-1/PD-L1 inhibitor use, irrespective of the treatment duration.
CONCLUSIONS: Sequential use of PD-1/PD-L1 inhibitors and EGFR-TKIs in patients with non-small cell lung cancer was significantly associated with IP compared to EGFR-TKIs without prior PD-1/PD-L1 inhibitor administration.
METHODS: We identified 69,107 eligible patients with non-small cell lung cancer (NSCLC) from a Japanese national inpatient database, who initiated EGFR-TKI therapy. The study population was divided into the PD-1/PD-L1 inhibitor and non-prior PD-1/PD-L1 groups based on PD-1/PD-L1 administration before EGFR-TKI therapy. We conducted 1:4 matched-pair cohort analyses (n = 9,725) to compare the incidence of IP and in-hospital mortality within 90 days of administration of EGFR-TKI between the two groups after adjusting for the clinical background. Furthermore, we performed subgroup analyses categorized according to the duration of prior PD-1/PD-L1 inhibitor use.
RESULTS: IP occurred in 4.4% of patients in the matched-pair cohort. PD-1/PD-L1 inhibitor-use before EGFR-TKI therapy was significantly associated with IP (odds ratio [OR], 1.79; 95% confidence interval [CI], 1.34-2.38) and in-hospital mortality (OR, 2.10; 95% CI, 1.72-2.55). Prior PD-1/PD-L1 inhibitor use in an interval of <6 months before EGFR-TKI administration was associated with a higher risk of IP than EGFR-TKI administration without prior PD-1/PD-L1 inhibitor. In-hospital mortality was higher in patients with prior PD-1/PD-L1 inhibitor use than that in those without prior PD-1/PD-L1 inhibitor use, irrespective of the treatment duration.
CONCLUSIONS: Sequential use of PD-1/PD-L1 inhibitors and EGFR-TKIs in patients with non-small cell lung cancer was significantly associated with IP compared to EGFR-TKIs without prior PD-1/PD-L1 inhibitor administration.
摘要：
背景：目前尚不清楚序贯给予程序性死亡（PD）-1/程序性死亡配体1（PD-L1）抑制剂和表皮生长因子受体-酪氨酸激酶抑制剂（EGFR-TKIs）是否与严重间质性肺炎（IP）的发生有关。
方法：我们从日本国家住院患者数据库中确定了69,107例非小细胞肺癌（NSCLC）的合格患者，谁开始EGFR-TKI治疗。根据EGFR-TKI治疗前的PD-1/PD-L1给药，将研究人群分为PD-1/PD-L1抑制剂和非PD-1/PD-L1抑制剂组。我们进行了1:4配对队列分析（n=9,725），以比较两组在调整临床背景后90天内使用EGFR-TKI的IP发生率和住院死亡率。此外，我们根据之前PD-1/PD-L1抑制剂使用的持续时间进行了亚组分析.
结果：配对队列中4.4%的患者发生IP。EGFR-TKI治疗前使用PD-1/PD-L1抑制剂与IP显著相关(比值比[OR]，1.79；95%置信区间[CI]，1.34-2.38)和住院死亡率(OR，2.10；95%CI，1.72-2.55）。与未使用PD-1/PD-L1抑制剂的EGFR-TKI相比，在EGFR-TKI施用前<6个月间隔内使用PD-1/PD-L1抑制剂与IP的风险更高。先前使用PD-1/PD-L1抑制剂的患者的住院死亡率高于先前未使用PD-1/PD-L1抑制剂的患者，无论治疗时间如何。
结论：在非小细胞肺癌患者中，PD-1/PD-L1抑制剂和EGFR-TKIs的顺序使用与IP显著相关，与之前没有PD-1/PD-L1抑制剂给药的EGFR-TKIs相比。
方法：我们从日本国家住院患者数据库中确定了69,107例非小细胞肺癌（NSCLC）的合格患者，谁开始EGFR-TKI治疗。根据EGFR-TKI治疗前的PD-1/PD-L1给药，将研究人群分为PD-1/PD-L1抑制剂和非PD-1/PD-L1抑制剂组。我们进行了1:4配对队列分析（n=9,725），以比较两组在调整临床背景后90天内使用EGFR-TKI的IP发生率和住院死亡率。此外，我们根据之前PD-1/PD-L1抑制剂使用的持续时间进行了亚组分析.
结果：配对队列中4.4%的患者发生IP。EGFR-TKI治疗前使用PD-1/PD-L1抑制剂与IP显著相关(比值比[OR]，1.79；95%置信区间[CI]，1.34-2.38)和住院死亡率(OR，2.10；95%CI，1.72-2.55）。与未使用PD-1/PD-L1抑制剂的EGFR-TKI相比，在EGFR-TKI施用前<6个月间隔内使用PD-1/PD-L1抑制剂与IP的风险更高。先前使用PD-1/PD-L1抑制剂的患者的住院死亡率高于先前未使用PD-1/PD-L1抑制剂的患者，无论治疗时间如何。
结论：在非小细胞肺癌患者中，PD-1/PD-L1抑制剂和EGFR-TKIs的顺序使用与IP显著相关，与之前没有PD-1/PD-L1抑制剂给药的EGFR-TKIs相比。
