ALK+ 非小细胞肺癌靶向治疗与血栓形成的相关性：系统评价和网络荟萃分析。

Correlation between ALK+ non-small cell lung cancer targeted therapy and thrombosis: a systematic review and network meta-analysis.

机构信息

Department of Respiratory Medicine, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.

Department of Respiratory Medicine, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, China

出版信息

BMJ Open. 2024 Sep 30;14(9):e078173. doi: 10.1136/bmjopen-2023-078173.

DOI:10.1136/bmjopen-2023-078173

PMID:39349372

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11448140/

Abstract

OBJECTIVE

The main adjuvant therapies for anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer include ALK tyrosine kinase inhibitors (TKI) and chemotherapy. We aimed to compare differences in the incidence of thromboembolism (TE) among different treatment options.

DESIGN

Using a systematic review and Bayesian network meta-analysis (NMA).

DATA SOURCES

We searched PubMed, Embase, Cochrane Library, ClinicalTrials.gov and Web of Science databases before 10 June 2023.

ELIGIBILITY CRITERIA

We included published randomised controlled trials (RCT) involving comparisons of treatments between chemotherapy and ALK-TKI drugs.

DATA EXTRACTION AND SYNTHESIS

Assessed risk bias with Cochrane tool. Conducted NMA with GEMTC in R, we evaluate the model fit using the deviation information criteria. Estimated posterior distribution using Markov Chain Monte Carlo, 4 chains, 10 fine-tuned iterations, 10 000 iterations per chain, total 50 000 iterations. Monitored potential scale reduction factor for convergence. And checked convergence with Gelman-Rubin statistics and trace plot. Provided surface under the cumulative ranking, lower values indicate less TE event probability.

RESULTS

Analysis of eight RCTs showed that, compared with that for crizotinib, there was a lower risk of total TE with chemotherapy (OR, 0.28; 95% credible intervals (CrI) 0.11 to 0.63), brigatinib (OR 0.31; 95% CrI 0.11 to 0.79) and ceritinib (OR 0.13; 95% CrI 0.03 to 0.45). In addition, analysis of venous TE (VTE) showed similar results, with a lower occurrence for chemotherapy (OR 0.27; 95% CrI 0.1 to 0.62), brigatinib (OR 0.18; 95% CrI 0.04 to 0.6) and ceritinib (OR 0.1; 95% CrI 0.02 to 0.43) compared with that for crizotinib. There were no significant differences in the occurrence of arterial TE among the different treatment options.

CONCLUSION

Compared with chemotherapy, alectinib, lorlatinib, brigatinib and ceritinib, crizotinib significantly increased the risk of TE and VTE.

PROSPERO REGISTRATION NUMBER

CRD42023373307.

摘要

目的

间变性淋巴瘤激酶（ALK）阳性非小细胞肺癌的主要辅助治疗包括 ALK 酪氨酸激酶抑制剂（TKI）和化疗。我们旨在比较不同治疗方案中血栓栓塞（TE）发生率的差异。

设计

采用系统评价和贝叶斯网络荟萃分析（NMA）。

数据来源

我们于 2023 年 6 月 10 日前检索了 PubMed、Embase、Cochrane 图书馆、ClinicalTrials.gov 和 Web of Science 数据库。

入选标准

纳入了比较化疗与 ALK-TKI 药物治疗的治疗方法的已发表随机对照试验（RCT）。

数据提取和综合

使用 Cochrane 工具评估风险偏倚。我们在 R 中使用 GEMTC 进行 NMA，使用偏差信息标准评估模型拟合度。使用马尔可夫链蒙特卡罗法估计后验分布，4 个链，10 次微调迭代，每个链 10000 次迭代，总迭代 50000 次。监测潜在的比例缩减因子以评估收敛性。使用 Gelman-Rubin 统计量和迹线图检查收敛性。提供累积排序曲线下面积，较低的值表示 TE 事件的概率较低。

结果

对八项 RCT 的分析表明，与克唑替尼相比，化疗的总 TE 风险较低（OR，0.28；95%可信区间（CrI）0.11 至 0.63），布加替尼（OR，0.31；95% CrI 0.11 至 0.79）和塞瑞替尼（OR，0.13；95% CrI 0.03 至 0.45）。此外，对静脉血栓栓塞症（VTE）的分析也得到了类似的结果，与克唑替尼相比，化疗（OR，0.27；95% CrI 0.1 至 0.62）、布加替尼（OR，0.18；95% CrI 0.04 至 0.6）和塞瑞替尼（OR，0.1；95% CrI 0.02 至 0.43）的 VTE 发生率较低。不同治疗方案之间动脉 TE 的发生无显著差异。