目的:间变性淋巴瘤激酶酪氨酸激酶抑制剂(ALKTKIs)在非小细胞肺癌(NSCLC)患者中显示出显著的临床活性。然而,肺炎是NSCLC患者ALKTKIs的严重副作用。在这个荟萃分析中,我们旨在确定ALK-TKI相关性肺炎的发生率.
方法:我们搜索了电子数据库,以确定直到2022年8月发表的相关研究。当没有观察到实质性异质性时,使用固定效应模型计算肺炎的发生率。否则,使用随机效应模型。对不同治疗组进行亚组分析。使用STATA17.0进行统计分析。
结果:涉及4752名患者的26项临床试验符合分析条件。所有级别肺炎发生率为2.92%(95%置信区间[CI]:1.79%-4.27%),高级别(3-4级)肺炎发生率为1.42%(95%CI:0.84%-2.12%),5级肺炎发生率为0.09%(95%CI:0.00%-0.28%).亚组分析显示,布格替尼与全级别和高级别肺炎的发生率最高(7.09%和3.06%,分别)。与一线ALKTKI治疗相比,化疗后ALKTKI治疗的全级别和高级别肺炎发生率更高(7.73%vs.2.26%和3.64%与1.26%,分别)。来自日本试验的队列具有较高的全级别和高级别肺炎发生率。
结论:我们的研究提供了接受ALKTKIs治疗的患者肺炎发生率的精确数据。总的来说,ALKTKIs具有可耐受的肺毒性。需要早期肺炎的识别和治疗,以防止接受布格替尼治疗的患者和先前接受化疗的患者进一步恶化。特别是在日本人口中。
Anaplastic lymphoma kinase tyrosine kinase inhibitors (ALK TKIs) have shown remarkable clinical activity in patients with non-small-cell lung cancer (NSCLC). However, pneumonitis is a serious side effect of ALK TKIs in NSCLC patients. In this meta-analysis, we aimed to determine the incidence of ALK-TKI-associated pneumonitis.
We searched electronic databases to identify relevant studies published until August 2022. The incidence of pneumonitis was calculated using a fixed-effects model when no substantial heterogeneity was observed. Otherwise, a random-effects model was used. Subgroup analyses of different treatment groups were performed. Statistical analyses were conducted using STATA 17.0.
Twenty-six clinical trials involving 4752 patients were eligible for analysis. All-grade pneumonitis incidence was 2.92% (95% confidence interval [CI]: 1.79%-4.27%), high-grade (Grade 3-4) pneumonitis incidence was 1.42% (95% CI: 0.84%-2.12%) and Grade 5 pneumonitis incidence was 0.09% (95% CI: 0.00%-0.28%). The subgroup analysis showed that brigatinib was associated with the highest incidence of both all-grade and high-grade pneumonitis (7.09% and 3.06%, respectively). ALK TKI treatment after chemotherapy was associated with a higher incidence of all-grade and high-grade pneumonitis than first-line ALK TKI treatment (7.73% vs. 2.26% and 3.64% vs. 1.26%, respectively). Cohorts from Japanese trials had a higher incidence of all-grade and high-grade pneumonitis.
Our study provides precise data on the incidence of pneumonitis in patients receiving treatment with ALK TKIs. Overall, ALK TKIs have tolerable pulmonary toxicity. Early pneumonitis identification and treatment are required to prevent further deterioration in patients receiving treatment with brigatinib and in those who received prior chemotherapy, particularly in the Japanese population.