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
- 1Department of Oncology, Beijing Tiantan Hospital, Capital Medical University
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.
Methods: 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).
Results: 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.
Conclusions: 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.
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BibTeX
@article{wu2026multimodality,
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}},
author = {Qichao Wu and Lei Qiu and Juan An and Weiran Xu and Xiaosheng Ding and Hui Shi and Yichun Hua and Xixi Zheng and Yijia Guo and Beihe Cao and Xiaoyan Li},
journal = {Frontiers in Immunology},
year = {2026},
month = oct,
doi = {10.3389/fimmu.2026.1973923},
url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1973923/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - 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
AU - Qichao Wu
AU - Lei Qiu
AU - Juan An
AU - Weiran Xu
AU - Xiaosheng Ding
AU - Hui Shi
AU - Yichun Hua
AU - Xixi Zheng
AU - Yijia Guo
AU - Beihe Cao
AU - Xiaoyan Li
PY - 2026
DA - 2026/10/05
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.1973923
UR - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1973923/full
AB - 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. Methods: 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). Results: 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. Conclusions: 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.
SN - 1664-3224
ER -