Clinical Epidemiology and Ageing

Efficacy of Osimertinib in EGFR-Mutated Non-Small Cell Lung Cancer with Leptomeningeal Metastases Pretreated with EGFR-Tyrosine Kinase Inhibitors.

Saboundji K, Auliac J-B, Perol M, François G, Janicot H, Marcq M, Dubos-Arvis C, Renault A, Guisier F, Odier L, Gervais R, Chouaid C Target Oncol. 2018;13(4):501-507.

BACKGROUND: The prognosis of patients with non-small cell lung cancer (NSCLC) who develop leptomeningeal metastasis (LM) is poor.

OBJECTIVE: To assess the clinical efficacy of osimertinib, a third-generation tyrosine-kinase inhibitor (TKI), in patients with epidermal growth-factor receptor (EGFR)-mutated NSCLCs and LM.

PATIENTS AND METHODS: Retrospective study of NSCLC patients with osimertinib-treated EGFR-mutated NSCLC and LM.

RESULTS: Twenty patients (mean age, 61.2 years; 70% women) with adenocarcinoma NSCLC were included in the study. EGFR mutations were reported in exons 18 (n = 2), 19 (n = 7), and 21 (n = 11). Before starting osimertinib, patients had received a mean of 2.3 treatment lines. When LM was diagnosed, all patients had clinical symptoms. Sixteen (80%) patients had a performance status ≥2. At osimertinib initiation, 13 (65%) patients harbored the EGFR-T790M-resistance mutation. Osimertinib was started at 80 (n = 17), 160 (n = 2), or 40 mg/day (n = 1). All 13 (100%) patients with the T790M mutation and 4 (57%) of those without it obtained clinical responses. Among the 11 radiologically assessable patients, 9 (82%) responded, with 5 responses reported within 15 days after treatment initiation. Median overall survival and progression-free survival were 18.0 and 17.2 months, respectively, from the start of osimertinib.

CONCLUSIONS: In this non-selected population, osimertinib had remarkable efficacy in NSCLC patients with LM irrespective of the presence of the EGFR-T790M-resistance mutation. Osimertinib efficacy was rapid in several patients, even some with poor performance status.

MeSH terms: Acrylamides; Aniline Compounds; Antineoplastic Agents; Carcinoma, Non-Small-Cell Lung; ErbB Receptors; Female; Humans; Lung Neoplasms; Male; Meningeal Carcinomatosis; Middle Aged; Mutation; Protein Kinase Inhibitors; Retrospective Studies
DOI: 10.1007/s11523-018-0581-2