既往糖尿病限制晚期肺癌免疫检查点抑制剂治疗后的生存率：日本的一项回顾性研究
Pre-Existing Diabetes Limits Survival Rate After Immune Checkpoint Inhibitor Treatment for Advanced Lung Cancer: A Retrospective Study in Japan.
作者信息
Hisanaga Kaori, Uchino Hiroshi, Kakisu Naoko, Miyagi Masahiko, Yoshikawa Fukumi, Sato Genki, Isobe Kazutoshi, Kishi Kazuma, Homma Sakae, Hirose Takahisa
机构信息
Division of Diabetes, Metabolism and Endocrinology, Department of Medicine, Toho University Graduate School of Medicine, Tokyo, Japan.
Department of Respiratory Medicine, Toho University Graduate School of Medicine, Tokyo, Japan.
出版信息
Diabetes Metab Syndr Obes. 2021 Feb 22;14:773-781. doi: 10.2147/DMSO.S289446. eCollection 2021.
BACKGROUND
Although immune checkpoint inhibitors (ICIs) are promising in the treatment of advanced cancer, their use is associated with immune-related adverse events (irAEs) that affect endocrine organ systems. Although development of irAEs was associated with improved cancer-specific survival, the risk of irAEs is unclear. We investigated the association of pre-ICI comorbidities-including diabetes-with irAEs, overall survival (OS), and progression-free survival (PFS) in advanced lung cancer.
METHODS
Patients with lung cancer who were treated with ICIs during the period from September 1, 2015 through July 31, 2018 were retrospectively enrolled. All data were collected from the NEPTUNE database of university patients. Hazard ratios were estimated by using Cox regression weighted for propensity scores. Odds ratios were calculated by logistic regression and adjusted for unbalanced variables. The Kaplan-Meier method was used to compare OS, and the generalized Wilcoxon test was used to compare median survival.
RESULTS
Among the 88 patients identified, 22 (25.0%) had diabetes (DM) before ICI treatment and 57 (75.0%) did not (non-DM); irAEs developed in 12.2% of patients with DM and in 9.1% of patients in non-DM (p=0.87). Diabetes status was not associated with irAE risk in relation to baseline characteristics (age, sex, TNM staging, thyroid and renal function) or in propensity score-matched analysis (age, TNM staging). During a mean follow-up of 30 months, OS and cancer-specific PFS were significantly higher in patients who developed irAEs (Kaplan-Meier estimates, p=0·04 and 0·03, respectively). In propensity score-matched analysis, diabetes was significantly associated with lower OS (multivariate hazard ratio, 0·36; 95% CI, 0·13-0·98) unrelated to irAEs. Irrespective of irAEs, PFS was also lower among patients with DM than among non-DM patients (Kaplan-Meier estimate, p=0·04).
CONCLUSION
Pre-existing diabetes was associated with higher mortality in advanced lung cancer, regardless of irAE development during treatment with ICI.
背景
尽管免疫检查点抑制剂（ICI）在晚期癌症治疗中前景广阔，但其使用与影响内分泌器官系统的免疫相关不良事件（irAE）有关。虽然irAE的发生与癌症特异性生存率的提高有关，但irAE的风险尚不清楚。我们研究了ICI治疗前的合并症（包括糖尿病）与晚期肺癌患者irAE、总生存期（OS）和无进展生存期（PFS）之间的关联。
方法
回顾性纳入2015年9月1日至2018年7月31日期间接受ICI治疗的肺癌患者。所有数据均从大学患者的海王星数据库中收集。使用倾向评分加权的Cox回归估计风险比。通过逻辑回归计算比值比，并对不平衡变量进行校正。采用Kaplan-Meier方法比较OS，采用广义Wilcoxon检验比较中位生存期。
结果
在纳入的88例患者中，22例（25.0%）在ICI治疗前患有糖尿病（DM），57例（75.0%）未患糖尿病（非DM）；DM患者中12.2%发生了irAE，非DM患者中9.1%发生了irAE（p = 0.87）。糖尿病状态与irAE风险在基线特征（年龄、性别、TNM分期、甲状腺和肾功能）方面或倾向评分匹配分析（年龄、TNM分期）中均无关联。在平均30个月的随访期间，发生irAE的患者的OS和癌症特异性PFS显著更高（Kaplan-Meier估计值，分别为p = 0.04和0.03）。在倾向评分匹配分析中，糖尿病与较低的OS显著相关（多变量风险比，0.36；95%置信区间，0.13 - 0.98），与irAE无关。无论是否发生irAE，DM患者的PFS也低于非DM患者（Kaplan-Meier估计值，p = 0.04）。
结论
无论ICI治疗期间是否发生irAE，既往糖尿病与晚期肺癌患者较高的死亡率相关。
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