Renaud Descourt1, Maurice Perol2, Gaëlle Rousseau-Bussac3, David Planchard4, Bertrand Mennecier5, Marie Wislez6, Alexis Cortot7, Florian Guisier8, Loïck Galland9, Pascal Dô10, Roland Schott11, Eric Dansin12, Jennifer Arrondeau13, Jean-Bernard Auliac3, Christos Chouaid3. 1. Centre Hospitalier Universitaire, Oncology Department, Brest, France. Electronic address: renaud.descourt@chu-brest.fr. 2. Léon Bérard Cancer Center, Lyon, France. 3. CHIC Créteil, Créteil, France. 4. Gustave Roussy, Department of Medical Oncology, Thoracic Group, Villejuif, France. 5. Centre Hospitalier Universitaire de Strasbourg, Chest Department, Strasbourg, France. 6. AP-HP, Hôpitaux Universitaires de l'Est Parisien, Tenon Hospital, Chest Department, Paris, France; AP-HP, Hôpitaux Universitaires Paris Centre, Cochin Hospital, Thoracic Oncology Unit, Department of Pneumology, Paris, France. 7. Centre Hospitalier Universitaire de Lille, Thoracic Oncology Unit, Lille, France. 8. Centre Hospitalier Universitaire de Rouen, Chest Department, Rouen, France. 9. Georges-François-Leclerc Cancer Center, Medical Oncology Department, Dijon, France. 10. François-Baclesse Cancer Center, Medical Oncology Department, Caen, France. 11. Paul-Strauss Cancer Center, Medical Oncology Department, Strasbourg, France. 12. Oscar-Lambret Cancer Center, Medical Oncology Department, Lille, France. 13. AP-HP, Hôpitaux Universitaires Paris Centre, Cochin Hospital, Thoracic Oncology Unit, Department of Pneumology, Paris, France.
Abstract
OBJECTIVES: Brigatinib is a next-generation ALK inhibitor initially developed in ALK-positive NSCLC pretreated with crizotinib. MATERIALS AND METHODS: This retrospective multicentric study analyzed ALK-positive advanced NSCLC patients pretreated with at least one tyrosine-kinase inhibitor, including crizotinib, and enrolled in the brigatinib French early access program. The primary endpoint was investigator-assessed progression-free survival (PFS). RESULTS: 104 patients were included (mean age, 56.6 years; never smokers, 61.5%; adenocarcinoma, 98.1%). Patients had received a median of 3 previous treatment lines, including at least 2 ALK inhibitors (mainly crizotinib then ceritinib). At brigatinib initiation, 59.1% had performance status 0-1, 51.9% had ≥ 3 metastatic sites, 74.5% had central nervous system metastases (CNS) and 8.8% had carcinomatous meningitis. Median duration of brigatinib treatment was 6.7 (95% CI, 0.06-20.7) months. Median PFS was 6.6 (4.8-9.9) months for the entire population. For patients who received 2, 3-4 and >4 lines of treatment before brigatinib, PFS was 4.3 (2.5-8.9), 10.4 (5.9-13.9) and 3.8 (0.8-7.4) months, respectively. In the 91 evaluable patients, disease control rate was 78.2%. From brigatinib start, median overall survival was 17.2 (11.0-not reached) months. Among the 68 patients with progressive disease after brigatinib, CNS was involved in 29.4% of cases. Median OS from the diagnosis of NSCLC was 75.3 (38.2-174.6) months. CONCLUSION: These real-world results confirm the efficacy of brigatinib in a cohort of patients heavily pretreated for ALK-positive advanced NSCLC.
OBJECTIVES:Brigatinib is a next-generation ALK inhibitor initially developed in ALK-positive NSCLC pretreated with crizotinib. MATERIALS AND METHODS: This retrospective multicentric study analyzed ALK-positive advanced NSCLCpatients pretreated with at least one tyrosine-kinase inhibitor, including crizotinib, and enrolled in the brigatinib French early access program. The primary endpoint was investigator-assessed progression-free survival (PFS). RESULTS: 104 patients were included (mean age, 56.6 years; never smokers, 61.5%; adenocarcinoma, 98.1%). Patients had received a median of 3 previous treatment lines, including at least 2 ALK inhibitors (mainly crizotinib then ceritinib). At brigatinib initiation, 59.1% had performance status 0-1, 51.9% had ≥ 3 metastatic sites, 74.5% had central nervous system metastases (CNS) and 8.8% had carcinomatous meningitis. Median duration of brigatinib treatment was 6.7 (95% CI, 0.06-20.7) months. Median PFS was 6.6 (4.8-9.9) months for the entire population. For patients who received 2, 3-4 and >4 lines of treatment before brigatinib, PFS was 4.3 (2.5-8.9), 10.4 (5.9-13.9) and 3.8 (0.8-7.4) months, respectively. In the 91 evaluable patients, disease control rate was 78.2%. From brigatinib start, median overall survival was 17.2 (11.0-not reached) months. Among the 68 patients with progressive disease after brigatinib, CNS was involved in 29.4% of cases. Median OS from the diagnosis of NSCLC was 75.3 (38.2-174.6) months. CONCLUSION: These real-world results confirm the efficacy of brigatinib in a cohort of patients heavily pretreated for ALK-positive advanced NSCLC.