Prognostic value of smoking status in non-small-cell lung cancer patients treated with immune checkpoint inhibitors: a meta-analysis

Jung Han Kim _, Hyeong Su Kim and Bum Jun Kim

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Oncotarget. 2017; 8:93149-93155. https://doi.org/10.18632/oncotarget.18703

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Jung Han Kim1,*, Hyeong Su Kim1,* and Bum Jun Kim1

1Division of Hemato-Oncology, Department of Internal Medicine, Kangnam Sacred-Heart Hospital, Hallym University Medical Center, Hallym University College of Medicine, Seoul 07441, Republic of Korea

*These authors contributed equally to this work

Correspondence to:

Jung Han Kim, email: [email protected], [email protected]

Keywords: non-small-cell lung cancer, immune checkpoint inhibitor, smoking, meta-analysis

Received: April 04, 2017     Accepted: June 11, 2017     Published: June 28, 2017


Immune checkpoint inhibitors (ICIs) have emerged as a new treatment option for patients with advanced non-small-cell lung cancer (NSCLC). Some studies with ICIs in NSCLC suggested that smoking history was associated with improved survival outcomes. We conducted this meta-analysis to investigate if survival benefits of ICIs in patients with advanced NSCLC are different according to smoking status. Electronic databases were searched for eligible studies. We included randomized controlled trials with the data of survival outcomes and extracted progression-free survival (PFS) or overall survival (OS) stratified by smoking status. From 6 studies, 2,389 ever-smokers and 413 never-smokers were included in the meta-analysis. In first-line treatment setting, ICIs tended to improve PFS in patients with smoking history (HR = 0.85 [95% CI, 0.71–1.10], P = 0.07). For never-smokers with advanced NSCLC, chemotherapy, not ICIs, was significantly associated with improvement of PFS (HR = 2.30 [95% CI, 1.23–4.28], P = 0.009). In more than second-line setting, ICIs significantly prolonged OS over that with chemotherapy in ever-smokers (HR = 0.70 [95% CI, 0.63–0.79], P < 0.00001). For never-smokers with NSCLC, however, ICIs failed to significantly improve OS (HR = 0.79 [95% CI, 0.59–1.06], P = 0.12). In conclusion, this meta-analysis indicates that ICIs can prolong survival over that with chemotherapy in ever-smokers with advanced NSCLC. However, ICIs failed to improve survival in never-smokers. These results suggest that smoking status may be a predictive marker for survival benefits to ICIs.

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