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Activity of EGFR Tyrosine Kinase Inhibitors in NSCLC With Refractory Leptomeningeal Metastases
- Source :
- Journal of Thoracic Oncology, Journal of Thoracic Oncology, Lippincott, Williams & Wilkins, 2019, 14, pp.1400-1407. ⟨10.1016/j.jtho.2019.05.007⟩, Journal of Thoracic Oncology, 14(8), 1400-1407. Elsevier Science, Journal of Thoracic Oncology, 2019, 14, pp.1400-1407. ⟨10.1016/j.jtho.2019.05.007⟩
- Publication Year :
- 2019
- Publisher :
- Elsevier Science, 2019.
-
Abstract
- Introduction: Leptomeningeal metastases (LMs) are associated with dismal prognosis in NSCLC. Optimal management remains unknown in patients with EGFR-mutated NSCLC after initial tyrosine kinase inhibitor (TKI) failure.Methods: We conducted a multicenter retrospective study including patients with EGFR-mutated NSCLC and LM. TKI failure was defined as diagnosis of LM on TKI, or progression of known LM on TKI.Results: Ninety-two patients were included, median age of 60 years, predominantly female (68%), never-smokers (74%). EGFR mutations included L858R (45%), exon 19 deletions (28%), or other mutations (14%). Median time to LM diagnosis was 18.5 months after initial diagnosis of advanced NSCLC. LM was diagnosed after a median of 2 (range: 0-9) systemic therapies. Median overall survival from LM diagnosis was 6.1 months (95% confidence interval [ CI]: 4.2-7.6 months). Among 87 patients with TKI failure, patients rechallenged with TKI (n = 50) had a median LM overall survival of 7.6 months (95% CI: 5.7-10.9) compared to 4.2 months (95% CI: 1.6-6.7) in patients without further therapy. Overall, 60% of patients rechallenged with TKI experienced clinical benefit (clinical response or stable disease >2 months), and 23% were treatment failure-free at 6 months. Clinical benefit was reported in 11 of 20 (55%) patients treated with erlotinib after afatinib or gefitinib. Strategies based on increasing dose intensity (n = 17) yielded clinical benefit in 59% of patients. All four patients who received osimertinib after first-and second-generation TKI experienced clinical benefit.Conclusions: TKI rechallenge strategies, including dosing intensification, may improve clinical outcomes of patients with LM from EGFR-mutated NSCLC after initial TKI failure. (C) 2019 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.
- Subjects :
- 0301 basic medicine
Pulmonary and Respiratory Medicine
Oncology
Male
medicine.medical_specialty
Lung Neoplasms
medicine.drug_class
Afatinib
[SDV]Life Sciences [q-bio]
EGFR
CELL LUNG-CANCER
BRAIN METASTASES
Tyrosine kinase inhibitor
NSCLC
Tyrosine-kinase inhibitor
03 medical and health sciences
0302 clinical medicine
Gefitinib
Refractory
Internal medicine
Carcinoma, Non-Small-Cell Lung
medicine
Humans
Osimertinib
Dosing
Protein Kinase Inhibitors
Retrospective Studies
Leptomeningeal metastases
business.industry
Retrospective cohort study
Middle Aged
Survival Analysis
respiratory tract diseases
3. Good health
ErbB Receptors
030104 developmental biology
Treatment Outcome
DOSE WEEKLY ERLOTINIB
030220 oncology & carcinogenesis
Mutation
Female
Erlotinib
business
Meningeal Carcinomatosis
medicine.drug
Subjects
Details
- Language :
- English
- ISSN :
- 15561380 and 15560864
- Volume :
- 14
- Issue :
- 8
- Database :
- OpenAIRE
- Journal :
- Journal of Thoracic Oncology
- Accession number :
- edsair.doi.dedup.....511ce6023917bed9c979e64c0a2db523