吸烟状况对接受分子靶向治疗或免疫治疗与化疗的非小细胞肺癌患者无进展生存期的影响：一项荟萃分析。

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.

机构信息

Department of Pharmacy Administration and Clinical Pharmacy, School of Pharmaceutical Sciences, Peking University, Beijing, China.

International Research Center for Medicinal Administration, Peking University, Beijing, China.

出版信息

J Clin Pharm Ther. 2021 Apr;46(2):256-266. doi: 10.1111/jcpt.13309. Epub 2020 Nov 5.

DOI:10.1111/jcpt.13309

PMID:33152129

Abstract

WHAT IS KNOWN AND OBJECTIVE

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).

METHODS

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.

RESULTS AND DISCUSSION

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).

WHAT IS NEW AND CONCLUSION

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.

摘要

已知和目的

吸烟对肺癌药物疗效有显著影响。先前的研究表明吸烟与一线表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKIs）的疗效之间存在相关性。吸烟者在免疫治疗中的获益仍存在争议。在这里，我们研究了吸烟对非小细胞肺癌（NSCLC）中分子靶向治疗或免疫治疗的临床结局的影响。

方法

我们进行了荟萃分析，纳入了比较 EGFR-TKIs、间变性淋巴瘤激酶（ALK）抑制剂或免疫检查点抑制剂（ICI）与化疗治疗 NSCLC 的试验。两组的无进展生存期（PFS）-风险比（HRs）作为指标，我们使用随机效应来汇总结果。

结果和讨论

选择了 20 项随机试验。与化疗相比，EGFR-TKIs 治疗在从不吸烟者（PFS：HR=0.46，95%CI 0.30 至 0.69）和吸烟者（PFS：HR=0.68，95%CI 0.50 至 0.91；p=0.135）中具有相似的获益，而从不吸烟者（PFS：HR=0.32，95%CI 0.23 至 0.44）比吸烟者（PFS：HR=0.54，95%CI 0.41 至 0.71；p=0.02）从一线 EGFR-TKIs 治疗中获益更好。ALK 抑制剂治疗在从不吸烟者（PFS：HR=0.43，95%CI 0.35 至 0.53）和吸烟者（PFS：HR=0.56，95%CI 0.44 至 0.71；p=0.406）中具有相似的获益。ICI 治疗在吸烟者（PFS：HR=0.79，95%CI 0.64 至 0.98）中的获益明显大于从不吸烟者（PFS：HR=1.81，95%CI 1.27 至 2.57；p=0.004）。

创新与结论

吸烟状况是 NSCLC 治疗的重要临床预测因素。与化疗相比，从不吸烟者和吸烟者使用 EGFR-TKIs 治疗具有相似的获益，而从不吸烟者在一线 EGFR-TKIs 治疗后获益更大。与化疗相比，ALK 抑制剂在从不吸烟者和吸烟者中的获益相似。此外，ICI 治疗在一线和二线治疗中均可使吸烟者的 PFS 更有利。