Title :

Activity of epidermal growth factor tyrosine kinase inhibitors in non-small cell lung carcinoma with refractory leptomeningeal metastases

Author(s) :

Flippot, Ronan [Auteur]
Biondani, Pamela [Auteur]
Auclin, Edouard [Auteur]
Xiao, Dingyu [Auteur]
Hendriks, Lizza [Auteur]
Le Rhun, Emilie [Auteur]
Centre Hospitalier Régional Universitaire [Lille] [CHRU Lille]
University hospital of Zurich [Zurich]
Département de Neurochirurgie[Lille]
Leduc, Charlotte [Auteur]
Beau-Faller, Michele [Auteur]
Gervais, Radj [Auteur]
Remon, Jordi [Auteur]
Adam, Julien [Auteur]
Planchard, David [Auteur]
Lavaud, Pernelle [Auteur]
Naltet, Charles [Auteur]
Caramella, Caroline [Auteur]
Le Pechoux, Cecile [Auteur]
Lacroix, Ludovic [Auteur]
Gazzah, Anas [Auteur]
Mezquita, Laura [Auteur]
Besse, Benjamin [Auteur]

Journal title :

Journal of thoracic oncology . official publication of the International Association for the Study of Lung Cancer

Abbreviated title :

J Thorac Oncol

Publication date :

2019-05-17

ISSN :

1556-1380

Keyword(s) :

Leptomeningeal metastases
Tyrosine kinase inhibitor
EGFR
NSCLC

HAL domain(s) :

Sciences du Vivant [q-bio]

English abstract : [en]

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. ...
Show more >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.Show less >

Language :

Anglais

Audience :

Internationale

Popular science :

Non

Administrative institution(s) :

INSERM
Université de Lille

Collections :

• Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U1192

Submission date :

2022-06-15T13:59:05Z
2023-04-21T12:47:36Z