Impact of EGFR tyrosine kinase inhibitors versus chemotherapy on the development of leptomeningeal metastasis in never smokers with advanced adenocarcinoma of the lung
Abstract
This study investigated whether epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI) increase the development of leptomeningeal metastasis (LM) compared with standard chemotherapy in EGFR mutation-enriched non- small cell lung cancer. The incidence of LM was longitudinally assessed in never smokers with advanced adenocarcinoma of the lung enrolled in a phase III randomized controlled study that compared gefitinib with gemcitabine plus cisplatin (GP) as first-line therapy (The First-SIGNAL study). Among 203 patients who were enrolled at the National Cancer Center Hospital (Goyang, Republic of Korea), LM occurred in 32 (15.8 %) with a minimum follow-up time of 55.1 months. The 1-, 2-, and 3-year actuarial incidence rates of LM were 5.3, 10.6, and 24.6 %, respectively. During first-line treatment, LM occurred in 2 patients (2.0 %) treated with gefitinib and in 3 patients (3.2 %) treated with GP. There was no difference in the incidence of LM during first-line treatment between the two groups (P = 0.934). The incidence of LM was significantly increased during second-line EGFR-TKI treatment compared with first-line EGFR-TKI treatment (P = 0.041). During the disease course, the cumulative incidence of LM was not significantly different between the two treatment groups (P = 0.514). The median time to LM was 21.4 and 24.0 months in the gefitinib and GP groups, respectively (P = 0.895). Similar trends were observed in the subset analysis with 23 EGFR-mutant patients. In conclusion, LM predominantly occurred in the late phase of disease in this population. EGFR-TKIs did not affect the incidence or timing of LM development.
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EGFR TKIs have shown promising efficacy in the treatment of leptomeningeal disease.
“EGFR TKIs have shown promising efficacy in the treatment of leptomeningeal disease.117,118”
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- Authors
- Lee, Y., Han, J.-Y., Kim, H. T., Yun, T., Lee, G. K., Kim, H. Y., & Lee, J. S.
- Affiliations
- National Cancer Center (KR)
- Corresponding author
- Lee, Jin Soo
- Venue
- Journal of Neuro-Oncology
- Published
- 2013-07-06
- Volume
- 115
- Issue
- 1
- Pages
- 95-101
- ISSN
- 0167-594X (ISSN-L)
- 1573-7373
- OpenAlex
- W2085731393
- Cited by
- 36
- References
- 19
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 3 · 2023: 1 · 2022: 5 · 2021: 1 · 2020: 5 · 2019: 4 · 2018: 5 · 2017: 1 · 2016: 3 · 2015: 4 · 2014: 2
- FWCI
- 2.44
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Journal of Neuro-Oncology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Brain Metastases and Treatment
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Diagnosis and Treatment
- Keywords
- leptomeningeal metastasis, EGFR tyrosine kinase inhibitors, gefitinib, gemcitabine plus cisplatin, non-small cell lung cancer, lung adenocarcinoma, never smokers, EGFR mutation, first-line therapy
- MeSH terms
- Gefitinib, Gemcitabine, Adenocarcinoma, Aged, Antineoplastic Combined Chemotherapy Protocols, Cisplatin, Deoxycytidine, Female, Follow-Up Studies, Humans, Lung Neoplasms, Male, Meningeal Neoplasms, Neoplasm Staging, Prognosis, Quinazolines, Survival Rate, Disease Progression, Protein Kinase Inhibitors, ErbB Receptors
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