Impact of Smoking History on Response to Immunotherapy in Non-Small-Cell Lung Cancer: A Systematic Review and Meta-Analysis

Zhao, Wenhua; Jiang, Wei; Wang, Huilin; He, Jianbo; Su, Cuiyun; Qin, Yu

doi:10.3389/fonc.2021.703143

Cited by 33 publications

(36 citation statements)

References 61 publications

(44 reference statements)

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“…A recent meta-analysis by Dai et al [ 100 ] found that ICI monotherapy and dual ICIs improved survival in ever smokers but not never smokers, regardless of PD-L1, and that the addition of chemotherapy was able to improve survival for both groups. Several real-world studies and analyses further support these observed associations [ 101 , 102 , 103 ].…”

Section: Future Directions To Understanding Tobacco Use and Ici Outcomesmentioning

confidence: 70%

Tobacco Use and Response to Immune Checkpoint Inhibitor Therapy in Non-Small Cell Lung Cancer

Corke

Leighl

et al. 2022

Current Oncology

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Tobacco is a known risk factor for lung cancer, and continued tobacco use is associated with poorer outcomes across multiple lung cancer treatment modalities including surgery, chemotherapy and radiation therapy. Less is known about the association of tobacco use and outcomes with immune checkpoint inhibitors (ICIs), which are becoming an important part of the treatment landscape in lung cancer, both in metastatic and curative settings. We reviewed the literature on the association of tobacco and tumor biology as it relates to immunotherapy. We also reviewed the association of tobacco use on outcomes among phase III randomized clinical trials involving ICIs in non-small cell lung cancer (NSCLC). We identified that patients with a smoking history may have a greater benefit with ICI treatment compared to never smokers in both treatment-naïve (HR 0.82, 95% CI 0.69–0.97, vs. HR 1.06, 95% CI 0.81–1.38) and pre-treated (HR 0.79, 95% CI 0.70–0.90 vs. 1.03, 95% CI 0.74–1.43) settings. In trials where smoking status was further defined, ex-smokers appear to demonstrate greater benefit with ICI therapy compared to current smokers (HR 0.78, 95% CI 0.59–1.01 vs. 0.91, 95% CI 0.72–1.14). We conclude by offering our perspective on future directions in this area of research, including implementation of standardized collection and analysis of tobacco use in clinical trials involving ICI therapy in lung cancer and other disease sites, and also evaluating how tobacco may affect toxicities related to ICI therapy. Based on our review, we believe that a patient’s history of tobacco smoking does have a role to play in guiding treatment decision making in patients with lung cancer.

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Section: Future Directions To Understanding Tobacco Use and Ici Outcomesmentioning

confidence: 70%

Tobacco Use and Response to Immune Checkpoint Inhibitor Therapy in Non-Small Cell Lung Cancer

Corke

Leighl

et al. 2022

Current Oncology

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“…We also found that smoking status was an independent factor for OS. Patients who have smoked might have more mutant antigens causing lung cancer, which has been revealed in previous studies of immunotherapy ( 30 , 31 ). Subgroup analysis of immunotherapy in patients with EGFR/ALK-negative NSCLC with SMS-low showed significantly better PFS than those with SMS-high.…”

Section: Discussionmentioning

confidence: 71%

A Somatic Mutation Signature Predicts the Best Overall Response to Anti-programmed Cell Death Protein-1 Treatment in Epidermal Growth Factor Receptor/Anaplastic Lymphoma Kinase-Negative Non-squamous Non-small Cell Lung Cancer

et al. 2022

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BackgroundWe aimed to exploit a somatic mutation signature (SMS) to predict the best overall response to anti-programmed cell death protein-1 (PD-1) therapy in non-small cell lung cancer (NSCLC).MethodsTumor samples of 248 patients with epidermal growth factor receptor (EGFR)/anaplastic lymphoma kinase (ALK)-negative non-squamous NSCLC treated with anti-PD-1 were molecularly tested by targeted next-generation sequencing or whole exome sequencing. On the basis of machine learning, we developed and validated a predictive model named SMS using the training (n = 83) and validation (n = 165) cohorts.ResultsThe SMS model comprising a panel of 15 genes (TP53, PTPRD, SMARCA4, FAT1, MGA, NOTCH1, NTRK3, INPP4B, KMT2A, PAK1, ATRX, BCOR, KDM5C, DDR2, and ARID1B) was built to predict best overall response in the training cohort. The areas under the curves of the training and validation cohorts were higher than those of tumor mutational burden and PD-L1 expression. Patients with SMS-high in the training and validation cohorts had poorer progression-free survival [hazard ratio (HR) = 6.01, P < 0.001; HR = 3.89, P < 0.001] and overall survival (HR = 7.60, P < 0.001; HR = 2.82, P < 0.001) than patients with SMS-low. SMS was an independent factor in multivariate analyses of progression-free survival and overall survival (HR = 4.32, P < 0.001; HR = 3.07, P < 0.001, respectively).ConclusionThis study revealed the predictive value of SMS for immunotherapy best overall response and prognosis in EGFR/ALK-negative non-squamous NSCLC as a potential biomarker in anti-PD-1 therapy.

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“…On the one hand, it is well-known that smoking is of great importance in the morbidity and mortality of lung cancer ( Loeb et al, 1984 ; Jung et al, 2016 ). On the other hand, the impact of smoking on treatment decisions is controversial and is recently being widely investigated ( Lin et al, 2018 ; Li et al, 2020 ; Xiao et al, 2020 ; Chen et al, 2021 ; Zhao et al, 2021 ). To our knowledge, the comprehensive and systematic analysis of the relationship between smoking status and first-line treatment efficacy of advanced ALK-positive NSCLC has not been reported yet.…”

Section: Discussionmentioning

confidence: 99%

“…Tobacco use impairs the treatment efficacy of lung cancer and shortens patients’ survival as smoking tobacco directly influences response to anti-tumor drugs by affecting drugs metabolism ( Gemine and Lewis, 2016 ). On the contrary, immunotherapy performs better in NSCLC patients with a smoking history ( Li et al, 2020 ; Nie et al, 2020 ; Zhao et al, 2021 ). Notably, both studies in the Asian-only subgroup used alectinib, despite dosage differences, which may suggest the excellent efficacy of alectinib in smokers, while the experimental ALK-TKIs in another group dramatically varied in multiracial studies.…”

Section: Discussionmentioning

confidence: 99%

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

Lin

Huang

et al. 2022

Front. Pharmacol.

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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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Impact of Smoking History on Response to Immunotherapy in Non-Small-Cell Lung Cancer: A Systematic Review and Meta-Analysis

Cited by 33 publications

References 61 publications

Tobacco Use and Response to Immune Checkpoint Inhibitor Therapy in Non-Small Cell Lung Cancer

Tobacco Use and Response to Immune Checkpoint Inhibitor Therapy in Non-Small Cell Lung Cancer

A Somatic Mutation Signature Predicts the Best Overall Response to Anti-programmed Cell Death Protein-1 Treatment in Epidermal Growth Factor Receptor/Anaplastic Lymphoma Kinase-Negative Non-squamous Non-small Cell Lung Cancer

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

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