AUTHOR=Lin Kehai , Lin Jie , Huang Zhong , Fu Jiding , Yi Qi , Cai Jiazuo , Khan Muhammad , Yuan Yawei , Bu Junguo 

TITLE=Impact of Smoking on Response to the First-Line Treatment of Advanced ALK-Positive Non-Small Cell Lung Cancer: A Bayesian Network Meta-Analysis

JOURNAL=Frontiers in Pharmacology

VOLUME=Volume 13 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2022.881493

DOI=10.3389/fphar.2022.881493

ISSN=1663-9812

ABSTRACT=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 1st-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 5th Jan 2022. Progression-free survival (PFS) was considered as the main outcome of interest. Randomized controlled trials with smoking status analysis were included. Cochrane Risk of Bias Tool was performed to assess study 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 2484 patients from 9 studies were eligible for this study, with 1547 never-smokers (62.3%) and 937 smokers (37.7%). In pairwise meta-analysis, in the overall population, no significant difference was found between never-smokers and smokers, but in the subgroup analyses based on crizotinib-controlled studies, anaplastic lymphoma kinase tyrosine kinase inhibitors (ALK-TKIs) derived better PFS in smoking group over never-smoking group in Asian population (HR=0.17, 95%CI=0.09-0.31 in smoking group, HR=0.39, 95%CI=0.24-0.65 in 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 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, 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 1st-line setting. However, alectinib may performed better in smoking Asian population. Moreover, lorlatinib in never-smokers and low-dose alectinib in smokers could be considered as 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.