CLINICAL TRIAL article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
This article is part of the Research TopicPrecision Immuno-Oncology: Harnessing Novel Drug Development, Biomarkers, and Nanoparticle-Based Therapeutic Platforms to Overcome Cancer ResistanceView all articles
Combination Immunotherapy and Anti-Angiogenic Therapy Shows Promising Efficacy in NSCLC Patients with Recurrent or Refractory Brain Metastases and Negative Driver Genes
Provisionally accepted
- 1Tianjin Huanhu Hospital, Tianjin, China
- 2Tianjin Marvelbio Technology Co., Ltd, Tianjin, China
- 3Tianjin Academy of Traditional Chinese Medicine Affiliated Hospital, Tianjin, China
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Introduction: This study aimed to evaluate the efficacy of immunotherapy combined with anti-angiogenic therapy for non-small cell lung cancer (NSCLC) with brain metastasis (BM) and negative driver genes. Methods: This observational prospective study was conducted using the clinical data of 34 patients with NSCLC and BM, including 24 patients who received immunotherapy combined with anti-angiogenic therapy and 10 control patients using oral anlotinib upon the first- to fourth-line treatment failure or refusing to continue chemotherapy between June 2017 and August 2022. Efficacy was evaluated by progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and adverse reactions. Results: Among 24 patients treated with immunotherapy combined with anti-angiogenic therapy, 17 had a partial response, 6 had stable disease, and 1 had progressive disease. The ORR and DCR of patients receiving immunotherapy combined with anti-angiogenic therapy were 70.8% and 95.8%, respectively. The median PFS of immunotherapy combined with anti-angiogenic treatment was significantly longer than that of oral anlotinib (18.0 vs. 4 months, log-rank test, p<0.0001), indicating that immunotherapy combined with anti-angiogenic therapy can substantially improve the treatment efficacy for NSCLC with BM and negative driver genes. Adverse reactions mainly included rash in one case and hypothyroidism in one case, but did not involve myocardial damage or liver and kidney function damage. Conclusion: Immunotherapy combined with anti-angiogenic therapy in patients with recurrent or refractory NSCL and BM driven by negative genes has yielded promising but preliminary findings. Clinical trial registration: www.chictr.org.cn; identifier: ChiCTR1800017499.
Keywords: Prospective observational study, Non-small cell lung cancer, brain metastasis, Immunotherapy, anti-angiogenic therapy
Received: 13 Aug 2025; Accepted: 18 Nov 2025.
Copyright: © 2025 Sun, Chen, Wang, Li, Li, Tian, Zhang, Liu and Liu. 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: Pengfei Liu, liupengfeitj@163.com
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