Activity of EGFR Tyrosine Kinase Inhibitors in NSCLC With Refractory Leptomeningeal Metastases

Ronan Flippot, Pamela Biondani, Edouard Auclin, Dingyu Xiao, Lizza Hendriks, Emilie Le Rhun, Charlotte Leduc, Michèle Beau-Faller, Radj Gervais, Jordi Remon, Julien Adam, David Planchard, Pernelle Lavaud, Charles Naltet, Caroline Caramella, Cécile Le Pechoux, Ludovic Lacroix, Anas Gazzah, Laura Mezquita, Benjamin Besse

    Résultats de recherche: Contribution à un journalArticleRevue par des pairs

    24 Citations (Scopus)

    Résumé

    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.

    langue originaleAnglais
    Pages (de - à)1400-1407
    Nombre de pages8
    journalJournal of Thoracic Oncology
    Volume14
    Numéro de publication8
    Les DOIs
    étatPublié - 1 août 2019

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