Elisa Gobbini1, Anne Claire Toffart2, Maurice Pérol3, Jean-Baptiste Assié4, Michaël Duruisseaux5, Dahna Coupez6, Catherine Dubos7, Virginie Westeel8, Myriam Delaunay9, Florian Guisier10, Rémi Veillon11, Valérie Gounant12, Etienne Giroux Leprieur13, François-Roger Vanel14, Nouha Chaabane15, Eric Dansin16, Hélène Babey17, Chantal Decroisette18, Fabrice Barlesi19, Catherine Daniel20, Pierre Fournel21, Laura Mezquita22, Youssef Oulkhouir23, Anthony Canellas24, Boris Duchemann25, Olivier Molinier26, Vincent Alcazer27, Denis Moro-Sibilot2, Matteo Giaj Levra2. 1. Thoracic Oncology Unit SHUPP, CHU Grenoble-Alpes, Grenoble, France; Cancer Research Center Lyon, Center Léon Bérard, Lyon, France. Electronic address: EGobbini@chu-grenoble.fr. 2. Thoracic Oncology Unit SHUPP, CHU Grenoble-Alpes, Grenoble, France. 3. Department of Medical Oncology, Léon Bérard Cancer Center, Lyon, France. 4. Thoracic Oncology Unit, CHU Créteil, Paris, France. 5. Unité de Recherche Commune en Oncologie Thoracique (URCOT), Hospices Civils de Lyon Cancer Institute, Lyon, France; Anticancer Antibodies Laboratory, Cancer Research Center of Lyon, Inserm 1052, CNRS 5286, Lyon, France; Université Claude Bernard Lyon 1, Université de Lyon, Lyon, France. 6. Thoracic Oncology Unit, CHU Nantes, Nantes, France. 7. Thoracic Oncology Unit, Center François Baclesse, Caen, France. 8. Thoracic Oncology Unit, CH Besançon, Besançon, France. 9. Pulmonology Department, CHU Toulouse, Toulouse, France. 10. Pneumology, Thoracic Oncology, and Respiratory Intensive Care Unit, CHU Rouen, Rouen, France. 11. Respiratory Diseases Department, F-33000, CHU Bordeaux, Bordeaux, France. 12. Thoracic Oncology Department, CIC 1425 INSERM, Center Bichat, Paris, France. 13. Department of Respiratory Diseases and Thoracic Oncology, APHP-Hôpital Ambroise Pare, Paris, France. 14. Thoracic Oncology Unit, CHU Strasbourg, Strasbourg, France. 15. Pulmonology Service, AP-HP Paris Center University Hospitals, Cochin Hospital, Paris, France. 16. Thoracic Oncology Unit, Center Oscar Lambret, Lille, France. 17. Thoracic Oncology Unit, CHRU Brest, Brest, France. 18. Pulmonology and Thoracic Oncology Unit, CH Annecy-Genevois, Annecy, France. 19. Aix-Marseille Université, CNRS, INSERM, CRCM, APHM, Marseille, France. 20. Thoracic Oncology Unit, Institute Curie, Paris/Saint Cloud, France. 21. Medical Oncology Department, Institut de Cancérologie de la Loire, Saint, France. 22. Department of Medical Oncology, Thoracic Group, Gustave Roussy, Villejuif, France. 23. Pulmonology and Thoracic Oncology Unit, CHU Caen, Caen, France. 24. Pulmonology Unit, APHP Hôpital Tenon and GRC 04 Theranoscan Sorbonne University, Paris, France. 25. Thoracic Oncology Unit, Center Bobigny, Paris, France. 26. Thoracic Oncology Unit, CH Le Mans, Le Mans, France. 27. Cancer Research Center Lyon, Center Léon Bérard, Lyon, France.
Abstract
BACKGROUND: Immune checkpoint inhibitor (ICPi) rechallenge could represent an attractive option in non-small-cell lung cancer (NSCLC), yet no sufficient data supporting this strategy are available. This retrospective observational multicenter national study explored the efficacy of anti-programmed cell death 1 (PD-1)/programmed death ligand 1 (PD-L1) rechallenge in advanced NSCLC patients, looking for potential clinical features associated with greater outcomes. PATIENTS AND METHODS: We retrospectively collected data from 144 advanced NSCLC patients whose disease was rechallenged with ICPis after ≥ 12 weeks of discontinuation. The progression-free survival (PFS) and overall survival (OS) were calculated from first or second ICPi initiation to disease progression (PFS1 and PFSR, respectively), death, or last follow-up (OS1, OSR), respectively. RESULTS: The median (interquartile range) age was 63 (58-70) years. Most patients were male (67%) and smokers (87%). Most had adenocarcinomas (62%) and/or stage IV disease at diagnosis (66%). The best response at rechallenge was not associated with that under the first ICPi (P = 1.10-1). The median (95% confidence interval) PFS1 and PFSR were 13 (10-16.5) and 4.4 (3-6.5) months, respectively. The median (95% confidence interval) OS1 and OSR were 3.3 (2.9-3.9) and 1.5 (1.0-2.1) years, respectively. Longer PFSR and OSR were found in patients discontinuing first ICPi because of toxicity or clinical decision, those not receiving systemic treatment between the two ICPis, and those with good Eastern Cooperative Oncology Group performance status at rechallenge. Only performance status proved to affect outcomes at multivariate analysis. CONCLUSION: Patients discontinuing first ICPi because of toxicity or clinical decision, those able to maintain a treatment-free period, and those with good performance status may be potential candidates for rechallenge.
BACKGROUND: Immune checkpoint inhibitor (ICPi) rechallenge could represent an attractive option in non-small-cell lung cancer (NSCLC), yet no sufficient data supporting this strategy are available. This retrospective observational multicenter national study explored the efficacy of anti-programmed cell death 1 (PD-1)/programmed death ligand 1 (PD-L1) rechallenge in advanced NSCLCpatients, looking for potential clinical features associated with greater outcomes. PATIENTS AND METHODS: We retrospectively collected data from 144 advanced NSCLCpatients whose disease was rechallenged with ICPis after ≥ 12 weeks of discontinuation. The progression-free survival (PFS) and overall survival (OS) were calculated from first or second ICPi initiation to disease progression (PFS1 and PFSR, respectively), death, or last follow-up (OS1, OSR), respectively. RESULTS: The median (interquartile range) age was 63 (58-70) years. Most patients were male (67%) and smokers (87%). Most had adenocarcinomas (62%) and/or stage IV disease at diagnosis (66%). The best response at rechallenge was not associated with that under the first ICPi (P = 1.10-1). The median (95% confidence interval) PFS1 and PFSR were 13 (10-16.5) and 4.4 (3-6.5) months, respectively. The median (95% confidence interval) OS1 and OSR were 3.3 (2.9-3.9) and 1.5 (1.0-2.1) years, respectively. Longer PFSR and OSR were found in patients discontinuing first ICPi because of toxicity or clinical decision, those not receiving systemic treatment between the two ICPis, and those with good Eastern Cooperative Oncology Group performance status at rechallenge. Only performance status proved to affect outcomes at multivariate analysis. CONCLUSION:Patients discontinuing first ICPi because of toxicity or clinical decision, those able to maintain a treatment-free period, and those with good performance status may be potential candidates for rechallenge.