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. 2021 Aug 23:11:703143.
doi: 10.3389/fonc.2021.703143. eCollection 2021.

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

Wenhua Zhao  1 , Wei Jiang  1 , Huilin Wang  1 , Jianbo He  1 , Cuiyun Su  1 , Qitao Yu  1
Affiliations

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

Wenhua Zhao et al. Front Oncol. .

Abstract

Objectives: To evaluate the impact of smoking history on the clinical benefit of immunotherapy in patients with non-small cell lung cancer (NSCLC).

Methods: Twenty-three randomized clinical trials and seven real-world studies were included in this meta-analysis. Hazard ratios (HRs) and 95% confidence intervals (CIs) for overall survival (OS) and progression-free survival (PFS) and odds ratios for the overall response rate (ORR) were extracted. A fixed-effects or random-effects model was applied to obtain pooled estimates.

Results: Data from 16 high-quality trials involving 10,643 NSCLC patients receiving either immunotherapy or chemotherapy/placebo enabled direct comparison of the survival impact of smoking. Anti-PD-1/PD-L1/CTLA-4 immunotherapy was found to significantly prolong OS and PFS as compared to chemotherapy/placebo in smokers (HR for OS, 0.76 [0.69-0.83], P<0.00001; HR for PFS, 0.65 [0.56-0.75], P<0.00001), and these trends were less or not significant in non-smokers (HR for OS, 0.91 [0.78-1.06], P=0.25; HR for PFS, 0.68 [0.45-1.03], P=0.07). Consistent results were obtained for the first-line or second/third-line use of immunotherapy and for non-squamous NSCLC patients only. Furthermore, the data from 7 trials and 7 real-world studies involving 4,777 patients receiving immunotherapy allowed direct comparison of therapeutic outcomes between smokers and non-smokers. Prolonged OS (HR 0.86 [0.75-0.99], P=0.04) and PFS (HR 0.69 [0.60-0.81], P<0.0001) and a higher response rate (ORR 1.20 [0.94-1.53], P=0.15) were observed in smokers compared to non-smokers receiving immunotherapy.

Conclusions: Immunotherapy was found to have a greater benefit in NSCLC patients with a smoking history than in those who had never smoked.

Keywords: clinical benefit; immunotherapy; meta-analysis; non-small cell lung cancer; smoking.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Flow chart of literature search strategy and study selection.
Figure 2
Figure 2
OS or PFS benefits of immunotherapy for NSCLC among smokers and non-smokers.
Figure 3
Figure 3
Comparison of Hazard Ratio regarding overall survival benefit (A) or progression free survival benefit (B) of immunotherapy vs chemo/placebo between smokers and non-smokers.
Figure 4
Figure 4
OS or PFS benefits from immunotherapy for non-squamous NSCLC among smokers and non-smokers.
Figure 5
Figure 5
OS or PFS benefits from immunotherapy as first-line treatment among smokers and non-smokers.
Figure 6
Figure 6
OS or PFS benefits from immunotherapy as second- or third-line treatment among smokers and non-smokers.
Figure 7
Figure 7
Funnel plot for publication bias of the direct comparison of HR-OS (A), HR-PFS (B) and ORR (C) between non-smokers and (C) smokers.
Figure 8
Figure 8
Direct comparison of immunotherapy outcomes between smokers and non-smokers with NSCLC.
See this image and copyright information in PMC

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