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.
Lung Cancer. 2018 Sep;123:60-69. doi: 10.1016/j.lungcan.2018.06.032. Epub 2018 Jun 30.
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.
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.
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.
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.
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。
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。
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%）。
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。
