The impact of smoking status on the progression-free survival of non-small cell lung cancer patients receiving molecularly target therapy or immunotherapy versus chemotherapy: A meta-analysis.

Abstract

Smoking has a notable influence on the efficacy of medications for lung cancer. Previous studies illustrated the correlation between smoking and the efficacy of first-line Epidermal Growth Factor Receptors-Tyrosine Kinase Inhibitors (EGFR-TKIs). The benefit of smokers in immunotherapy was still controversial. Here, we investigated the impact of smoking on clinical outcomes of molecularly targeted therapies or immunotherapy in Non-Small Cell Lung Cancer (NSCLC). We performed meta-analysis including trials comparing EGFR-TKIs, Anaplastic Lymphoma Kinase (ALK) inhibitors or Immune Checkpoint Inhibitors (ICIs) against chemotherapy in NSCLC. The Progression-Free Survival (PFS)-Hazard Ratios (HRs) of two groups served as the index and we used random effects to pool outcomes. Twenty randomized trials were selected. Compared with chemotherapy, treatment with EGFR-TKIs had similar benefit in never-smokers (PFS: HR=0.46, 95% CI 0.30 to 0.69) and smokers (PFS: HR=0.68, 95% CI 0.50 to 0.91; p=0.135) while non-smokers (PFS: HR=0.32, 95% CI 0.23 to 0.44) had better benefit from first-line EGFR-TKIs than smokers (PFS: HR=0.54, 95% CI 0.41 to 0.71; p=0.02). Treatment with ALK inhibitors had similar benefits in never-smokers (PFS: HR=0.43, 95% CI 0.35 to 0.53) and smokers (PFS: HR=0.56, 95% CI 0.44 to 0.71; p=0.406). The benefit of ICIs in smokers (PFS: HR=0.79, 95% CI 0.64 to 0.98) was significantly greater than never-smokers (PFS: HR=1.81, 95% CI 1.27 to 2.57; p=0.004). Smoking status is an important clinical predictor of therapy in NSCLC. Never-smokers and smokers have similar benefit with EGFR-TKIs therapy compared with chemotherapy, while never-smokers have greater benefit after first-line EGFR-TKIs therapy. There was similar benefit in never-smokers and smokers when using ALK inhibitors over chemotherapy. Additionally, ICIs treatment over chemotherapy leads to more favourable PFS in smokers both in first-line and second-line settings.