{
  "abstract": "Background: Leptomeningeal metastasis (LM) is among the most devastating modes of progression in EGFR-mutated non-small cell lung cancer (NSCLC). Although dose escalation of third-generation EGFR-TKIs has been an important central nervous system (CNS)-directed salvage strategy, therapeutic options after progression on this intensification approach remain limited.\n\nMethods: This single-center retrospective study included consecutive patients treated between September 2024 and December 2025. Eligible patients were adults (≥18 years) with histologically confirmed lung adenocarcinoma, a documented EGFR mutation, and LM diagnosed by gadolinium-enhanced MRI or positive cerebrospinal fluid (CSF) cytology. Patients received ivonescimab plus chemotherapy after documented intracranial or extracranial progression on a dose-escalated third-generation EGFR-TKI regimen used for LM management, with or without concurrent CSF-directed therapy. Ivonescimab was given intravenously at 20 mg/kg every 3 weeks with chemotherapy selected according to prior treatment and clinical status. The primary endpoints were overall survival (OS) and LM progression-free survival (LM-PFS).\n\nResults: Of 517 screened patients, 33 initiated ivonescimab plus chemotherapy and comprised the overall treated cohort. Concurrent intrathecal or intraventricular chemotherapy was administered to 29 of 33 patients (87.9%). The median age was 61 years (IQR 56–62); 24 (72.7%) were female; 24 (72.7%) had baseline ECOG performance status of 2–3. The median number of prior therapy lines was 4 (IQR 3–6). At a median follow-up of 8.28 months, median OS was 8.54 months (95% CI 5.75–14.32), median LM-PFS was 6.54 months (95% CI 3.42–11.86), and median systemic PFS was 4.83 months (95% CI 2.79–7.56). Three-month treatment persistence was 64.4% (95% CI 44.9–78.6). Among 29 patients evaluable for LM response, 6 achieved a response, yielding an LM response rate of 20.7% (95% CI 8.0–39.7) and an LM disease control rate of 82.8% (95% CI 64.2–94.2). Among 31 patients with evaluable safety documentation, grade ≥3 treatment-related adverse events occurred in 14 (45.2%), most commonly hematologic toxicities. No permanent ivonescimab discontinuation due to toxicity was documented.\n\nConclusions: This cohort provides real-world outcome data for patients with EGFR-mutated NSCLC and LM receiving multimodality salvage treatment incorporating ivonescimab plus chemotherapy after dose-escalated third-generation EGFR-TKI failure.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Oncology, Beijing Tiantan Hospital, Capital Medical University"
  ],
  "article_type": "research support, non u.s. gov't",
  "arxiv": null,
  "author_total": 11,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Qichao Wu"
    },
    {
      "affs": [
        0
      ],
      "name": "Lei Qiu"
    },
    {
      "affs": [
        0
      ],
      "name": "Juan An"
    },
    {
      "affs": [
        0
      ],
      "name": "Weiran Xu"
    },
    {
      "affs": [
        0
      ],
      "name": "Xiaosheng Ding"
    },
    {
      "affs": [
        0
      ],
      "name": "Hui Shi"
    },
    {
      "affs": [
        0
      ],
      "name": "Yichun Hua"
    },
    {
      "affs": [
        0
      ],
      "name": "Xixi Zheng"
    },
    {
      "affs": [
        0
      ],
      "name": "Yijia Guo"
    },
    {
      "affs": [
        0
      ],
      "name": "Beihe Cao"
    },
    {
      "affs": [
        0
      ],
      "name": "Xiaoyan Li"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/8wsdpw5692331.bib",
  "cited_by": 0,
  "doi": "10.3389/fimmu.2026.1973923",
  "fulltext_url": "https://europepmc.org/articles/PMC13677939",
  "id": "8wsdpw5692331",
  "issns": [
    "1664-3224"
  ],
  "landing_url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1973923/full",
  "language": "eng",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2740|Lung Cancer Treatments and Mutations"
    ]
  ],
  "openalex": "W7220457895",
  "pdf_url": "https://europepmc.org/articles/PMC13677939?pdf=render",
  "pmcid": "PMC13677939",
  "pmid": "42898404",
  "published": "2026-10-05",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/8wsdpw5692331.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:15Z",
      "native_id": "10.3389/fimmu.2026.1973923",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1973923/full"
    },
    {
      "first_seen": "2026-10-30T12:19:37Z",
      "native_id": "MED:42898404",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42898404"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "issn:1664-3224",
      "subfield": "immunology"
    }
  ],
  "title": "Multimodality salvage treatment incorporating ivonescimab plus chemotherapy for EGFR-mutated NSCLC with leptomeningeal metastases after dose-escalated third-generation EGFR-TKI failure: a retrospective study",
  "title_text": "Multimodality salvage treatment incorporating ivonescimab plus chemotherapy for EGFR-mutated NSCLC with leptomeningeal metastases after dose-escalated third-generation EGFR-TKI failure: a retrospective study",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:19:37Z",
  "url": "https://research.draconitic.com/paper/8wsdpw5692331",
  "venue": "Frontiers in Immunology",
  "versions": []
}