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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| Format: | Article |
| Language: | English |
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Wiley
2025-06-01
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| 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. |
| format | Article |
| id | doaj-art-21cd8d99a0b34a90972a877f159e55ee |
| institution | OA Journals |
| issn | 1759-7706 1759-7714 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Wiley |
| record_format | Article |
| series | Thoracic Cancer |
| 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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