Jaafar Bennouna1, Nicolas Girard2, Clarisse Audigier-Valette3, Aurélie le Thuaut4, Radj Gervais5, Philippe Masson6, Marie Marcq7, Olivier Molinier8, Alexis Cortot9, Didier Debieuvre10, Jacques Cadranel11, Hervé Lena12, Denis Moro-Sibilot13, Christos Chouaid14, Bertrand Mennecier15, Thierry Urban16, Christine Sagan17, Ludivine Perrier4, Fabrice Barlesi18, Marc G Denis19. 1. Thoracic Oncology Unit, Centre Hospitalier Universitaire Nantes, Nantes, France. Electronic address: jaafar.bennouna@univ-nantes.fr. 2. Thoracic Department, Institut Curie, Paris, France. 3. Department of Pneumology, Centre Hospitalier Toulon Sainte-Musse, Toulon, France. 4. Direction de la Recherche, Centre Hospitalier Universitaire Nantes, Nantes, France. 5. Medical Oncology, Centre François Baclesse, Caen, France. 6. Department of Pneumology, Centre Hospitalier Cholet, Cholet, France. 7. Department of Pneumology, CHD Vendée, La Roche sur Yon, France. 8. Department of Pneumology, Centre Hospitalier Le Mans, Le Mans, France. 9. Thoracic Oncology Department, Centre Hospitalier Universitaire Lille, Lille, France. 10. Department of Pneumology, GHRMSA - Hôpital Emile Miller, Mulhouse, France. 11. Department of Pneumology, APHP, Hôpital Tenon and GRC 04 Theranoscan, Sorbonne Université, Paris, France. 12. Department of Pneumology, Hôpital Pontchaillou, Rennes, France. 13. Thoracic Oncology Unit, Grenoble-Alpes University Hospital, Grenoble, France. 14. Department of Pneumology, CHI Creteil, Creteil, France. 15. Department of Pneumology, Centre Hospitalier Universitaire Strasbourg, Strasbourg, France. 16. Department of Pneumology, Centre Hospitalier Universitaire Angers, Angers, France. 17. Department of Anatomopathology, Centre Hospitalier Universitaire Nantes, Nantes, France. 18. Multidisciplinary Oncology and Therapeutic Innovations Department, Aix Marseille University, CNRS, INSERM, CRCM, APHM, Marseille, France. 19. Department of Biochemistry, Centre Hospitalier Universitaire Nantes, Nantes, France.
Abstract
BACKGROUND: Osimertinib, a third-generation tyrosine kinase inhibitor, is a new therapeutic option in epidermal growth factor receptor (EGFR)-mutated non-pretreated advanced non-small-cell lung cancer (NSCLC). The tumor escape mechanisms after first-line treatment with osimertinib are partially known; most of the data being obtained by analysis of circulating tumor DNA (ctDNA) from the FLAURA phase III trial. STUDY DESIGN: The MELROSE study, a French multicentric, open label, phase II trial (ClinicalTrials.govNCT03865511) plans to enroll 150 patients with treatment-naive advanced EGFR-mutated (L858R or exon 19 deletion) NSCLC, age ≥ 18 years, with an Eastern Cooperative Oncology Group performance status 0 or 1. All patients will receive osimertinib at the dose of 80 mg/d. Tumor assessment according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria will be performed every 3 months, with brain and thoracoabdominal computed tomographic scan. The continuation of osimertinib is at the discretion of the referring physician, particularly if clinical benefit is observed. The primary objective is the genetic tumor profile, both on tissue biopsy and ctDNA analyses, at the time of disease progression. Other endpoints include kinetic studies of ctDNA, biological progression-free survival (bPFS) (time from first study dose to first biological event on ctDNA), median PFS according to RECIST criteria 1.1 (called radiological [r] PFS), and median clinical (c) PFS (time from the first study dose to off-osimertinib). This study started in April 2019, and 18 centers in France are participants.
BACKGROUND: Osimertinib, a third-generation tyrosine kinase inhibitor, is a new therapeutic option in epidermal growth factor receptor (EGFR)-mutated non-pretreated advanced non-small-cell lung cancer (NSCLC). The tumor escape mechanisms after first-line treatment with osimertinib are partially known; most of the data being obtained by analysis of circulating tumor DNA (ctDNA) from the FLAURA phase III trial. STUDY DESIGN: The MELROSE study, a French multicentric, open label, phase II trial (ClinicalTrials.govNCT03865511) plans to enroll 150 patients with treatment-naive advanced EGFR-mutated (L858R or exon 19 deletion) NSCLC, age ≥ 18 years, with an Eastern Cooperative Oncology Group performance status 0 or 1. All patients will receive osimertinib at the dose of 80 mg/d. Tumor assessment according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria will be performed every 3 months, with brain and thoracoabdominal computed tomographic scan. The continuation of osimertinib is at the discretion of the referring physician, particularly if clinical benefit is observed. The primary objective is the genetic tumor profile, both on tissue biopsy and ctDNA analyses, at the time of disease progression. Other endpoints include kinetic studies of ctDNA, biological progression-free survival (bPFS) (time from first study dose to first biological event on ctDNA), median PFS according to RECIST criteria 1.1 (called radiological [r] PFS), and median clinical (c) PFS (time from the first study dose to off-osimertinib). This study started in April 2019, and 18 centers in France are participants.