Karima Saboundji1, Jean-Bernard Auliac2, Maurice Pérol3, Géraldine François4, Henri Janicot5, Marie Marcq6, Catherine Dubos-Arvis7, Aldo Renault8, Florian Guisier9, Luc Odier10, Radj Gervais7, Christos Chouaïd11. 1. Pneumologie et Oncologie Thoracique, CH François-Quesnay, 2, Boulevard de Sully, 78200, Mantes-la-Jolie, France. 2. Pneumologie et Oncologie Thoracique, CH François-Quesnay, 2, Boulevard de Sully, 78200, Mantes-la-Jolie, France. j-b.auliac@ch-mantes-la-jolie.fr. 3. Oncologie, Centre Léon-Bérard, Lyon, France. 4. Pneumologie et Oncologie Thoracique, CHU d'Amiens, Amiens, France. 5. Pneumologie, CHU Clermont-Ferrand, Clermont-Ferrand, France. 6. Pneumologie, CHU Vendée, La Roche-sur-Yon, France. 7. Oncologie, Centre François-Baclesse, Caen, France. 8. Pneumologie, CH François-Mitterrand, Pau, France. 9. Pneumologie, CHU Charles-Nicolle, Rouen, France. 10. Pneumologie, Hôpital Nord-Ouest, Villefranche-sur-Saône, France. 11. Pneumologie, CH Intercommunal de Créteil, Créteil, France.
Abstract
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.
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.
Authors: James C H Yang; Sang-We Kim; Dong-Wan Kim; Jong-Seok Lee; Byoung Chul Cho; Jin-Seok Ahn; Dae H Lee; Tae Min Kim; Jonathan W Goldman; Ronald B Natale; Andrew P Brown; Barbara Collins; Juliann Chmielecki; Karthick Vishwanathan; Ariadna Mendoza-Naranjo; Myung-Ju Ahn Journal: J Clin Oncol Date: 2019-12-06 Impact factor: 44.544