Abstract
ObjectivesTo evaluate the impact of smoking history on the clinical benefit of immunotherapy in patients with non-small cell lung cancer (NSCLC).MethodsTwenty-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.ResultsData 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.ConclusionsImmunotherapy was found to have a greater benefit in NSCLC patients with a smoking history than in those who had never smoked.
Highlights
Lung cancer remains a highly prevalent cancer and the leading cause of cancer-related death worldwide [1]
Immunotherapy was found to have a greater benefit in non-small cell lung cancer (NSCLC) patients with a smoking history than in those who had never smoked
We conducted a pooled analysis for direct comparison of the clinical benefit from immunotherapy between smokers and non-smokers with the data provided by 7 clinical trials and 7 real-world studies, which included 4,777 cases in total (Table 2)
Summary
Lung cancer remains a highly prevalent cancer and the leading cause of cancer-related death worldwide [1]. Continuous efforts have been made to improve outcomes in NSCLC patients, and some breakthroughs have been achieved in recent years, the most promising one being the development immunotherapy [2]. The basic approach of immunotherapy is to evoke an antitumor immune response by blocking an immune checkpoint, like programmed death-1/programmed death ligand-1 (PD-1/ PD-L1) and cytotoxic T-cell lymphocyte antigen-4, and thereby achieving durable control of a tumor [3]. Remarkable improvements in clinical outcomes in multiple cancer types have been achieved by immunotherapy [4], only a limited percentage of NSCLC patients respond to the therapy, with less than 30% of NSCLC patients benefiting from immunotherapy [5]. Efficient markers to identify NSCLC patients who are most likely to respond to immunotherapy are urgently needed
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