Real-World Evidence That Non-Smokers With High PD-L1 Non-Squamous NSCLC Have Poorer Outcomes With Immune Checkpoint Inhibitors.

IF 2.3 3区医学 Q3 ONCOLOGY

Thoracic Cancer Pub Date : 2025-09-01 DOI:10.1111/1759-7714.70167

Yu-Chu Kuo, Wen-Chien Cheng, Hsu-Yuan Chen, Chun-Ru Chien, Chih-Yen Tu, Hung-Jen Chen

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Abstract

Background: Immune checkpoint inhibitors (ICIs) improve outcomes in non-small cell lung cancer (NSCLC) with high PD-L1 expression, but biomarkers beyond PD-L1 are limited. Smoking-related immune activation may enhance ICI efficacy, yet evidence in non-squamous NSCLC, especially among non-smokers, is sparse.

Methods: We retrospectively analyzed 74 patients with Stage IIIB-IV non-squamous NSCLC, PD-L1 ≥ 50%, and no EGFR/ALK/ROS1 mutations, treated at a tertiary center in Taiwan (2017-2023). Patients were stratified by smoking status. Treatment responses, progression-free survival (PFS), and overall survival (OS) were evaluated using RECIST v1.1, Kaplan-Meier, and Cox regression.

Results: Among 74 patients, 54 (72.9%) were smokers and 20 (27.1%) were non-smokers. Compared with non-smokers, smokers had a higher partial response rate (66.7% vs. 25.0%, p = 0.001), longer median PFS (12.8 vs. 1.4 months, p = 0.001), and improved OS (47.1 vs. 10.0 months, p = 0.011). In the non-smoker subgroup, chemoimmunotherapy significantly prolonged PFS compared with ICI monotherapy (not reached vs. 1.4 months, p = 0.034). In multivariate analysis, smoking independently predicted better PFS (HR = 0.234, p = 0.001) and OS (HR = 0.229, p = 0.011).

Conclusion: Non-smokers with PD-L1-high non-squamous NSCLC showed significantly poorer outcomes with ICI monotherapy. Chemoimmunotherapy may be preferred in this group. Smoking history may provide a simple and clinically relevant stratification factor when considering ICI-based treatment.

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真实世界的证据表明，不吸烟的高PD-L1非鳞状NSCLC患者使用免疫检查点抑制剂的预后较差。

背景：免疫检查点抑制剂（ICIs）可改善PD-L1高表达的非小细胞肺癌（NSCLC）的预后，但PD-L1以外的生物标志物有限。吸烟相关的免疫激活可能会提高ICI的疗效，但在非鳞状非小细胞肺癌中，尤其是在非吸烟者中，证据很少。方法：我们回顾性分析了74例IIIB-IV期非鳞状NSCLC患者，PD-L1≥50%，无EGFR/ALK/ROS1突变，在台湾三级中心治疗（2017-2023）。根据吸烟状况对患者进行分层。使用RECIST v1.1、Kaplan-Meier和Cox回归评估治疗反应、无进展生存期（PFS）和总生存期（OS）。结果：74例患者中，吸烟54例（72.9%），不吸烟20例（27.1%）。与不吸烟者相比，吸烟者的部分缓解率更高（66.7% vs. 25.0%, p = 0.001），中位PFS更长（12.8 vs. 1.4个月，p = 0.001）， OS改善（47.1 vs. 10.0个月，p = 0.011）。在非吸烟者亚组中，与ICI单药治疗相比，化学免疫治疗显著延长了PFS（未达到vs. 1.4个月，p = 0.034）。在多变量分析中，吸烟独立预测更好的PFS （HR = 0.234, p = 0.001）和OS （HR = 0.229, p = 0.011）。结论：非吸烟者pd - l1高非鳞状NSCLC患者ICI单药治疗的预后明显较差。化疗免疫治疗可能是本组首选。当考虑以ici为基础的治疗时，吸烟史可能提供一个简单且与临床相关的分层因素。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Thoracic Cancer ONCOLOGY-RESPIRATORY SYSTEM

CiteScore

5.20

自引率

3.40%

发文量

439

审稿时长

2 months

期刊介绍： Thoracic Cancer aims to facilitate international collaboration and exchange of comprehensive and cutting-edge information on basic, translational, and applied clinical research in lung cancer, esophageal cancer, mediastinal cancer, breast cancer and other thoracic malignancies. Prevention, treatment and research relevant to Asia-Pacific is a focus area, but submissions from all regions are welcomed. The editors encourage contributions relevant to prevention, general thoracic surgery, medical oncology, radiology, radiation medicine, pathology, basic cancer research, as well as epidemiological and translational studies in thoracic cancer. Thoracic Cancer is the official publication of the Chinese Society of Lung Cancer, International Chinese Society of Thoracic Surgery and is endorsed by the Korean Association for the Study of Lung Cancer and the Hong Kong Cancer Therapy Society. The Journal publishes a range of article types including: Editorials, Invited Reviews, Mini Reviews, Original Articles, Clinical Guidelines, Technological Notes, Imaging in thoracic cancer, Meeting Reports, Case Reports, Letters to the Editor, Commentaries, and Brief Reports.