晚期非小细胞肺癌患者接受表皮生长因子受体酪氨酸激酶抑制剂治疗后的肺炎：153 个队列 15713 例患者的荟萃分析：非小细胞肺癌中表皮生长因子受体酪氨酸激酶抑制剂性肺炎的发生率和危险因素的荟萃分析。
Pneumonitis in advanced non-small-cell lung cancer patients treated with EGFR tyrosine kinase inhibitor: Meta-analysis of 153 cohorts with 15,713 patients: Meta-analysis of incidence and risk factors of EGFR-TKI pneumonitis in NSCLC.
机构信息
Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, 86 Asanbyeongwon-Gil, Songpa-Gu, Seoul 138-736, Republic of Korea.
Department of Radiology, Brigham and Women's Hospital and Dana-Farber Cancer Institute, Harvard Medical School, 450 Brookline Ave, Boston MA, USA.
出版信息
Lung Cancer. 2018 Sep;123:60-69. doi: 10.1016/j.lungcan.2018.06.032. Epub 2018 Jun 30.
PURPOSE
Pneumonitis is a significant toxicity of EGFR tyrosine kinase inhibitors (EGFR-TKI) in non-small-cell lung cancer (NSCLC) patients. We studied the incidence of pneumonitis in clinical trials of EGFR-TKI published in 2003-2017, and performed subgroups analyses to identity predisposing factors.
METHODS
Ovid-MEDLINE and EMBASE search up to 4/17/17 using the keywords, "erlotinib", "gefitinib", "afatinib", "osimertinib", and "lung cancer", resulted in a total of 153 eligible trial cohorts with 15,713 advanced NSCLC patients treated with EGFR-TKI. The pooled incidence of all-grade, high-grade, and grade 5 pneumonitis was obtained. Subgroup analyses were performed with meta-regression using study-level covariates.
RESULTS
Among the patients without prior exposure to EGFR-TKI, the overall incidence was 1.12% (95% CI:0.79-1.58%) for all-grade, 0.61% (95% CI:0.40-0.93%) for high-grade, and 0.20% (95% CI:0.11-0.38%) for grade 5 pneumonitis. The incidence was significantly higher in Japanese studies compared to studies of non-Japan origin, for all-grade (4.77% vs. 0.55%, p < 0.001), high grade (2.49% vs. 0.37%, p < 0.001), and grade 5 pneumonitis (1.00% vs. 0.18%, p < 0.001). Multivariate analyses demonstrated higher odds of pneumonitis in Japanese studies for all-grade (odds ratio [OR]: 5.04; 95% CI:3.14-8.11, p < 0.001), high-grade (OR: 4.45; 95% CI:2.50-7.93, p < 0.001), and grade 5 pneumonitis (OR: 4.55; 95% CI:2.20-9.44, p < 0.001) compared to others, after adjusting for types of EGFR-TKI and lines of therapy. In patients with EGFR retreatment analyzed separately, the pooled incidence was 1.13% (95% CI:0.40-3.15%) for all-grade, 0.49% (95% CI:0.21-1.11%) for high-grade, and 0.16% (95% CI:0.04-0.65%) for grade 5 pneumonitis.
CONCLUSIONS
The overall incidence of EGFR-TKI pneumonitis was 1.12% in patients without prior exposure to EGFR-TKI, and 1.13% in EGFR-TKI retreatment group. The cohorts from Japan had significantly higher incidence of pneumonitis, providing insights for further mechanistic studies.
目的
间质性肺炎是表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKI）在非小细胞肺癌（NSCLC）患者中的一种显著毒性。我们研究了 2003 年至 2017 年发表的 EGFR-TKI 临床试验中肺炎的发生率，并进行了亚组分析以确定易患因素。
方法
使用关键词“厄洛替尼”、“吉非替尼”、“阿法替尼”、“奥希替尼”和“肺癌”，在 Ovid-MEDLINE 和 EMBASE 上进行了截至 2017 年 4 月 17 日的搜索，共检索到 153 项符合条件的试验队列，包含 15713 名接受 EGFR-TKI 治疗的晚期 NSCLC 患者。获得所有等级、高级别和 5 级间质性肺炎的合并发生率。使用基于研究水平的协变量进行荟萃回归进行亚组分析。
结果
在没有预先暴露于 EGFR-TKI 的患者中，所有等级的总体发生率为 1.12%（95%CI：0.79-1.58%），高级别的发生率为 0.61%（95%CI：0.40-0.93%），5 级的发生率为 0.20%（95%CI：0.11-0.38%）。与非日本来源的研究相比，日本研究中肺炎的发生率明显更高，所有等级（4.77%比 0.55%，p<0.001）、高级别（2.49%比 0.37%，p<0.001）和 5 级肺炎（1.00%比 0.18%，p<0.001）。多变量分析表明，在日本研究中，肺炎的发生风险更高，所有等级（比值比[OR]：5.04；95%CI：3.14-8.11，p<0.001）、高级别（OR：4.45；95%CI：2.50-7.93，p<0.001）和 5 级肺炎（OR：4.55；95%CI：2.20-9.44，p<0.001），与其他研究相比，在调整了 EGFR-TKI 类型和治疗线数后。在单独分析 EGFR 再治疗的患者中，所有等级的合并发生率为 1.13%（95%CI：0.40-3.15%），高级别的发生率为 0.49%（95%CI：0.21-1.11%），5 级的发生率为 0.16%（95%CI：0.04-0.65%）。
结论
在没有预先暴露于 EGFR-TKI 的患者中，EGFR-TKI 性肺炎的总体发生率为 1.12%，在 EGFR-TKI 再治疗组中为 1.13%。来自日本的队列肺炎发生率明显更高，为进一步的机制研究提供了线索。
Zotero 插件