ORIGINAL RESEARCH article
Front. Oncol.
Sec. Thoracic Oncology
Volume 15 - 2025 | doi: 10.3389/fonc.2025.1533048
This article is part of the Research TopicAdvancing NSCLC Treatment: Overcoming Challenges in Immune Checkpoint Inhibitor TherapyView all 12 articles
First-line treatment options for PD-L1-negative lung adenocarcinoma: a real-world analysis
Provisionally accepted
- Department of Medical Oncology, Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, China
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Objective: To evaluate the optimal first-line treatment options for programmed death-ligand 1 (PD-L1) negative lung adenocarcinoma (LUAD) patients without common gene-alterations.Methods: A total of 159 PD-L1-negative LUAD patients without common gene-alterations were included. Chemotherapy was administered in 44 cases (group A), immunotherapy-chemotherapy combinations in 55 cases (group B) and bevacizumab plus chemotherapy in 60 patients (group C). A head-to-head comparison of the clinical effectiveness and safety for these standard treatment regimens was conducted.The median follow-up time was 30.9 months. For the entire cohort, median PFS was 6.67 months ], and median OS was 15.83 months [95% CI 13.46-18.21]. OS was significantly longer in group C versus others (C vs B median 21.6 months [95% CI 17.78-25.42] vs 12.63 months [95% CI 8.14-17.13]; HR 0.59 [95% CI 0.39-0.9], P = 0.01; C vs A median 21.6 months [95% CI 17.78-25.42] vs 13.47 months [95% CI 9.68-17.26], HR 0.47 [95% CI 0.3-0.71], P= 0.001), but no substantial difference was noted between group A and B (HR 0.78 [95% CI 0.51-1.2], P= 0.26). For PFS in pairwise comparison, group B and C were statistically superior to group A ( B vs A median 5.6 months [95% CI 4.56-6.64] vs 5.17 months [95% CI 4.09-6.25]; hazard ratio (HR) 0.56 [95% CI 0.37-0.87], P = 0.009; C vs A median 8.57 months [95% CI 7.47-9.66] vs 5.17 months [95% CI 4.09-6.25]; HR 0.43 [95% CI 0.28-0.7], P< 0.001), whereas no significant difference was found between group B and C (HR 0.76 [95% CI 0.51-1.11], P= 0.16). The disease control rate (DCR) improvement was sustained with group C (A vs B vs C: 84.09% vs 83.64% vs 96.67%, respectively (P<0.05)). Multivariate analysis showed that the performance status score and treatment regimen were factors influencing PFS as well as OS. The treatment-emergent adverse events (AEs) of grade 3-4 occurred in a similar proportion of patients in each group (P>0.05), and all AEs were manageable without fatal toxicities.Bevacizumab plus chemotherapy should be prioritized in PD-L1-negative LUAD patients without common driver gene alterations. These findings may facilitate individualized treatment options.
Keywords: Lung Adenocarcinoma, PD-L1 negative, First-line treatment, bevacizumab, Immunotherapy, prognosis
Received: 22 Nov 2024; Accepted: 12 May 2025.
Copyright: © 2025 Chen, LIU, Feng, Hu, An and Zhao. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Lijuan Chen, Department of Medical Oncology, Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, China
Erjing An, Department of Medical Oncology, Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, China
Yanqiu Zhao, Department of Medical Oncology, Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, China
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