First‐Line Immune‐Combination Therapy for Driver Gene‐Negative NSCLC With Brain Metastases: Real‐World Outcomes

ABSTRACT Background Optimal treatment for driver gene‐negative non‐small cell lung cancer (NSCLC) with brain metastases (BM) remains unclear, particularly regarding immune checkpoint inhibitor (ICI)‐based combinations and local BM therapy. Predictive biomarkers for intracranial efficacy are also und...

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Main Authors: Mengxing You, Lige Wu, Jiayu Liu, Hanqi Yuan, Zihe Wang, Xuezhi Hao, Puyuan Xing, Junling Li
Format: Article
Language:English
Published: Wiley 2025-06-01
Series:Thoracic Cancer
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Online Access:https://doi.org/10.1111/1759-7714.70095
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author Mengxing You
Lige Wu
Jiayu Liu
Hanqi Yuan
Zihe Wang
Xuezhi Hao
Puyuan Xing
Junling Li
author_facet Mengxing You
Lige Wu
Jiayu Liu
Hanqi Yuan
Zihe Wang
Xuezhi Hao
Puyuan Xing
Junling Li
author_sort Mengxing You
collection DOAJ
description ABSTRACT Background Optimal treatment for driver gene‐negative non‐small cell lung cancer (NSCLC) with brain metastases (BM) remains unclear, particularly regarding immune checkpoint inhibitor (ICI)‐based combinations and local BM therapy. Predictive biomarkers for intracranial efficacy are also undefined. Methods This retrospective study analyzed driver gene‐negative NSCLC patients with BM treated with first‐line ICI‐based systemic therapy (ICI plus chemotherapy [ICI + CT] or ICI + CT plus bevacizumab [ICI + CT + Bev]) from June 2019 to June 2024. The intracranial progression‐free survival (icPFS), progression‐free survival (PFS), and overall survival (OS) were compared between treatment groups and by BM local therapy. The PD‐L1 tumor proportion score (TPS) expression was evaluated for correlation with intracranial efficacy. Results A total of 36 patients were enrolled in the study. The intracranial objective response rate (icORR) was 70.6% (ICI + CT) versus 78.6% (ICI + CT + Bev) (p = 0.689), with no significant differences in icPFS, PFS, or OS between the two different first‐line systemic regimens (all p > 0.05). Local BM therapy (n = 18) did not improve icPFS and OS (all p > 0.05). Extracranial PD‐L1 (TPS ≥ 50%, n = 13) correlated with superior icPFS, PFS, and OS (all p < 0.05) versus PD‐L1 TPS < 50%. Multivariate analysis confirmed PD‐L1 ≥ 50% as an independent prognostic factor (HR = 0.155; 95% CI, 0.025–0.939; p = 0.042). Conclusions Adding bevacizumab to first‐line ICI‐chemotherapy did not enhance survival outcomes. Local treatment for BM did not provide additional survival advantages when combined with first‐line ICI‐based systemic therapy. Extracranial PD‐L1 TPS ≥ 50% predicted improved intracranial efficacy.
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spelling doaj-art-21cd8d99a0b34a90972a877f159e55ee2025-08-20T02:37:05ZengWileyThoracic Cancer1759-77061759-77142025-06-011611n/an/a10.1111/1759-7714.70095First‐Line Immune‐Combination Therapy for Driver Gene‐Negative NSCLC With Brain Metastases: Real‐World OutcomesMengxing You0Lige Wu1Jiayu Liu2Hanqi Yuan3Zihe Wang4Xuezhi Hao5Puyuan Xing6Junling Li7Department of Medical Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College Beijing ChinaDepartment of Medical Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College Beijing ChinaDepartment of Medical Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College Beijing ChinaDepartment of Medical Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College Beijing ChinaDepartment of Medical Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College Beijing ChinaDepartment of Medical Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College Beijing ChinaDepartment of Medical Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College Beijing ChinaDepartment of Medical Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College Beijing ChinaABSTRACT Background Optimal treatment for driver gene‐negative non‐small cell lung cancer (NSCLC) with brain metastases (BM) remains unclear, particularly regarding immune checkpoint inhibitor (ICI)‐based combinations and local BM therapy. Predictive biomarkers for intracranial efficacy are also undefined. Methods This retrospective study analyzed driver gene‐negative NSCLC patients with BM treated with first‐line ICI‐based systemic therapy (ICI plus chemotherapy [ICI + CT] or ICI + CT plus bevacizumab [ICI + CT + Bev]) from June 2019 to June 2024. The intracranial progression‐free survival (icPFS), progression‐free survival (PFS), and overall survival (OS) were compared between treatment groups and by BM local therapy. The PD‐L1 tumor proportion score (TPS) expression was evaluated for correlation with intracranial efficacy. Results A total of 36 patients were enrolled in the study. The intracranial objective response rate (icORR) was 70.6% (ICI + CT) versus 78.6% (ICI + CT + Bev) (p = 0.689), with no significant differences in icPFS, PFS, or OS between the two different first‐line systemic regimens (all p > 0.05). Local BM therapy (n = 18) did not improve icPFS and OS (all p > 0.05). Extracranial PD‐L1 (TPS ≥ 50%, n = 13) correlated with superior icPFS, PFS, and OS (all p < 0.05) versus PD‐L1 TPS < 50%. Multivariate analysis confirmed PD‐L1 ≥ 50% as an independent prognostic factor (HR = 0.155; 95% CI, 0.025–0.939; p = 0.042). Conclusions Adding bevacizumab to first‐line ICI‐chemotherapy did not enhance survival outcomes. Local treatment for BM did not provide additional survival advantages when combined with first‐line ICI‐based systemic therapy. Extracranial PD‐L1 TPS ≥ 50% predicted improved intracranial efficacy.https://doi.org/10.1111/1759-7714.70095brain metastasesdriver geneimmunotherapynon‐small cell lung cancerreal‐world study
spellingShingle Mengxing You
Lige Wu
Jiayu Liu
Hanqi Yuan
Zihe Wang
Xuezhi Hao
Puyuan Xing
Junling Li
First‐Line Immune‐Combination Therapy for Driver Gene‐Negative NSCLC With Brain Metastases: Real‐World Outcomes
Thoracic Cancer
brain metastases
driver gene
immunotherapy
non‐small cell lung cancer
real‐world study
title First‐Line Immune‐Combination Therapy for Driver Gene‐Negative NSCLC With Brain Metastases: Real‐World Outcomes
title_full First‐Line Immune‐Combination Therapy for Driver Gene‐Negative NSCLC With Brain Metastases: Real‐World Outcomes
title_fullStr First‐Line Immune‐Combination Therapy for Driver Gene‐Negative NSCLC With Brain Metastases: Real‐World Outcomes
title_full_unstemmed First‐Line Immune‐Combination Therapy for Driver Gene‐Negative NSCLC With Brain Metastases: Real‐World Outcomes
title_short First‐Line Immune‐Combination Therapy for Driver Gene‐Negative NSCLC With Brain Metastases: Real‐World Outcomes
title_sort first line immune combination therapy for driver gene negative nsclc with brain metastases real world outcomes
topic brain metastases
driver gene
immunotherapy
non‐small cell lung cancer
real‐world study
url https://doi.org/10.1111/1759-7714.70095
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