Efficacy of osimertinib combined with antiVEGF therapy ramucirumab in managing leptomeningeal metastasis in EGFR-mutant NSCLC - a case report and literature review

Sep 22, 2026

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Leptomeningeal metastasis (LM) is a severe complication of EGFR-mutant non-small cell lung cancer (NSCLC) with limited options and poor prognosis. Osimertinib has demonstrated central nervous system efficacy, while ramucirumab, a VEGFR-2 inhibitor, may improve penetration and response. A case report describes two EGFR-mutant NSCLC patients treated with osimertinib plus ramucirumab, showing marked neurologic recovery and radiologic regression, with only mild hypertension and rash. Conclusions support safety and potential effectiveness, warranting prospective validation.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages7

Reading Time18 min

AccessFree to download

Background

Leptomeningeal metastasis in EGFR-mutant NSCLC

Limitations of conventional therapies

Rationale for the combination

Osimertinib CNS activity

Ramucirumab’s potential to enhance delivery

Case presentation

Case 1

Case 2

Conclusions

Potential benefits and need for further studies

Tsai et al. Journal of Cardiothoracic Surgery (2026) 21:285 [https://doi.org/10.1186/s13019-026-03923-2](https://doi.org/10.1186/s13019-026-03923-2) Journal of Cardiothoracic Surgery CASE REPORT Open Access Efficacy of osimertinib combined with antiVEGF therapy ramucirumab in managing leptomeningeal metastasis in EGFR-mutant NSCLC: a case report and literature review Yueh-HsunTsai1, Yu-Shiou Weng2 and Tsai-Wang Huang1* Abstract Background Leptomeningeal metastasis (LM) is a severe complication of epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC), associated with limited treatment options and poor prognosis. Osimertinib, a third-generation EGFR tyrosine kinase inhibitor (TKI), has demonstrated central nervous system (CNS) efficacy, while ramucirumab, a VEGFR-2 inhibitor, may enhance drug penetration and therapeutic response. The combination has not been reported in LM. Case presentation We report two patients with EGFR-mutant NSCLC who developed LM and received osimertinib (80 mg/day) plus ramucirumab (10 mg/kg every 3 weeks) . A 79-year-old man with an EGFR exon 21 L858R mutation presented with progressive neurological symptoms and MRI-confirmed LM. Combination therapy led to marked clinical improvement, resolution of leptomeningeal enhancement, and stable disease for over 12 months, with only mild hypertension and rash. A 74-year-old woman with an EGFR exon 19 deletion and LM involving the brainstem also demonstrated significant neurological recovery, including regaining oral intake, radiologic regression of LM lesions, and durable control for more than one year. Adverse events were limited to mild dermatologic toxicity. Conclusions Although osimertinib has established activity in LM, outcomes remain suboptimal. Data from systemic disease suggest that combining EGFR and VEGF inhibition may further enhance efficacy, but LM-specific evidence has been lacking. These two cases highlight the potential of osimertinib plus ramucirumab as a safe and effective therapeutic approach in EGFR-mutant NSCLC with LM, providing durable neurologic and radiologic responses. Further prospective studies are warranted to validate these findings and better define the role of this regimen in LM management. Keywords Osimertinib, Ramucirumab, Leptomeningeal metastasis, Targeted therapy *Correspondence: Tsai-Wang Huang [chi-wang@yahoo.com.tw](chi-wang@yahoo.com.tw) 1Division of Thoracic Surgery, Department of Surgery, Tri-Service General Hospital, National Defense Medical University, No. 325, Sec. 2, Chengkung Rd., Neihu Dist. 114, Taipei 11490, Taiwan 2Department of Radiology, Tri-Service General Hospital, National Defense Medical University, Taipei 11490, Taiwan © The Author(s) 2026. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit [http://creati](http://creati)[vecommons.org/licenses/by-nc-nd/4.0/](vecommons.org/licenses/by-nc-nd/4.0/.)[.](vecommons.org/licenses/by-nc-nd/4.0/.) Tsai et al. Journal of Cardiothoracic Surgery (2026) 21:285 Background Leptomeningeal metastasis (LM)

FAQs

What is leptomeningeal metastasis (LM) and why is it clinically important in EGFR-mutant NSCLC?

LM is described as a serious complication occurring in a small proportion of patients with advanced NSCLC, particularly with EGFR mutations. It indicates advanced disease and is associated with poor prognosis, frequent neurologic symptoms, and declining quality of life.

How were the two patients treated in the case report?

The report describes two EGFR-mutant NSCLC patients receiving osimertinib 80 mg/day together with ramucirumab 10 mg/kg every 3 weeks.

What outcomes and adverse events were reported after combination therapy?

Both cases showed marked neurologic improvement and radiologic resolution or regression of leptomeningeal enhancement, with durable disease control for more than one year. Adverse events were limited to mild hypertension and rash/dermatologic toxicity.

Sep 22, 2026

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