Impact of Smoking on Response to the First-Line Treatment of Advanced ALK-Positive Non-Small Cell Lung Cancer: A Bayesian Network Meta-Analysis.
Impact of Smoking on Response to the First-Line Treatment of Advanced ALK-Positive Non-Small Cell Lung Cancer: A Bayesian Network Meta-Analysis.
复制标题
吸烟对晚期ALK阳性非小细胞肺癌一线治疗反应的影响：贝叶斯网络荟萃分析。
DOI：
10.3389/fphar.2022.881493
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发表时间：
2022
影响因子：
5.6
通讯作者：
Bu, Junguo
中科院分区：
文献类型：
--
作者：
Lin, Kehai;Lin, Jie;Huang, Zhong;Fu, Jiding;Yi, Qi;Cai, Jiazuo;Khan, Muhammad;Yuan, Yawei;Bu, Junguo
关键词：
背景：吸烟对间变性淋巴瘤激酶(ALK)阳性的非小细胞肺癌(NSCLC)治疗效果的影响是有争议的，而且还没有在一线环境下进行系统的探索。为了解决这个问题，我们进行了基于成对荟萃分析和贝叶斯网络荟萃分析(NMA)的系统综述。方法：检索PubMed、Embase、Web of Science、Cochrane图书馆、Clinic-Trials.gov等资源，直至2022年1月5日。无进展生存(PFS)被认为是令人感兴趣的主要结果。纳入吸烟状况分析的随机对照试验。使用Cochrane偏差风险工具评估偏差风险。Meta分析采用保守的随机效应模型。NMA是在贝叶斯框架内使用R-4.1.2软件的“Gemtc”1.0-1版程序包进行的。结果：共有9项研究的2484名患者符合这项研究，其中1547名从不吸烟者(62.3%)和937名吸烟者(37.7%)。在一项成对的荟萃分析中，在总体人群中，从不吸烟者和吸烟者之间没有发现显著差异。然而，在基于Crizotinib对照研究的亚组分析中，在亚洲人群中，间变性淋巴瘤激酶酪氨酸激酶抑制剂(ALK-TKIs)在吸烟组中比不吸烟组获得更好的PFS(吸烟组HR=0.17，95%CI=0.09-0.31，非吸烟组HR=0.39，95%CI=0.24-0.65，p=0.04，证据质量低)。在NMA中，非吸烟者中，劳拉替尼的PFS最高(SUCRA=96.2%)，但新一代ALK-TKI中，除Ceritinib外，没有发现明显的优势。在吸烟者中，小剂量阿莱替尼的效果最好(SUCRA=95.5%)，也明显优于恩沙替尼(HR=0.23，95%CI=0.08-0.68，证据质量很低)、布里加替尼(HR=0.38，95%CI=0.14-0.99，证据质量低)、Ceritinib(HR=0.24，95%CI=0.09-0.66，证据质量低)、Crizotinib(HR=0.18，95%CI=0.08-0.41，证据质量中等)，化疗(HR=0.11，95%CI=0.05~0.28，证据质量低)。结论：总的来说，吸烟可能不会影响一线治疗晚期ALK阳性非小细胞肺癌的疗效。然而，阿莱替尼在亚洲吸烟人群中的表现可能更好。此外，对从不吸烟的人使用劳拉替尼，对吸烟者使用小剂量的阿莱替尼，可以认为是治疗晚期ALK阳性非小细胞肺癌的最佳一线治疗方案。在这项NMA中，存在可接受的证据限制，如研究偏差、不一致和不精确的风险。
Background: The impact of smoking on the efficacy of anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) treatment is controversial and has not been systematically explored in the first-line setting. We performed a systematic review based on a pairwise meta-analysis and a Bayesian network meta-analysis (NMA) to address this issue. Methods: PubMed, Embase, Web of Science, Cochrane Library, Clinical-Trials.gov, and other resources were searched until 5 January 2022. Progression-free survival (PFS) was considered the main outcome of interest. Randomized controlled trials with smoking status analysis were included. Cochrane Risk of Bias Tool was performed to assess the risk of bias. Random effects models were adopted conservatively in meta-analysis. The NMA was performed in a Bayesian framework using the “gemtc” version 1.0–1 package of R-4.1.2 software. Results: A total of 2,484 patients from nine studies were eligible for this study, with 1,547 never-smokers (62.3%) and 937 smokers (37.7%). In a pairwise meta-analysis, in the overall population, no significant difference was found between never-smokers and smokers. However, in the subgroup analyses based on crizotinib-controlled studies, anaplastic lymphoma kinase tyrosine kinase inhibitors (ALK-TKIs) derived better PFS in the smoking group over the never-smoking group in the Asian population (HR = 0.17, 95%CI = 0.09–0.31 in the smoking group, HR = 0.39, 95%CI = 0.24–0.65 in the never-smoking group, p = 0.04, low quality of evidence). In NMA, among never-smokers, lorlatinib ranked the highest for PFS (SUCRA = 96.2%), but no significant superiority was found among the new-generation ALK-TKIs except for ceritinib. In smokers, low-dose alectinib performed best (SUCRA = 95.5%) and also demonstrated a significant superiority over ensartinib (HR = 0.23, 95%CI = 0.08–0.68, very low quality of evidence), brigatinib (HR = 0.38, 95%CI = 0.14–0.99, low quality of evidence), ceritinib (HR = 0.24, 95%CI = 0.09–0.66, low quality of evidence), crizotinib (HR = 0.18, 95%CI = 0.08–0.41, moderate quality of evidence), and chemotherapy (HR = 0.11, 95%CI = 0.05–0.28, low quality of evidence). Conclusion: In general, smoking may not affect the treatment efficacy of advanced ALK-positive NSCLC in the first-line setting. However, alectinib may perform better in the smoking Asian population. Moreover, lorlatinib in never-smokers and low-dose alectinib in smokers could be considered optimal first-line therapy for advanced ALK-positive NSCLC. Acceptable limitations of evidence, such as study risk of bias, inconsistency, and imprecision, were present in this NMA.
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