A Randomized Non-Comparative Phase II Study of Anti-Programmed Cell Death-Ligand 1 Atezolizumab or Chemotherapy as Second-Line Therapy in Patients With Small Cell Lung Cancer: Results From the IFCT-1603 Trial |
| |
| Authors: | Jean-Louis Pujol Laurent Greillier Clarisse Audigier-Valette Denis Moro-Sibilot Lionel Uwer José Hureaux Florian Guisier Delphine Carmier Jeannick Madelaine Josiane Otto Valérie Gounant Patrick Merle Pierre Mourlanette Olivier Molinier Aldo Renault Audrey Rabeau Martine Antoine Marc G Denis Pierre-Jean Souquet |
| |
| Institution: | 1. Department of Thoracic Oncology, Montpellier Regional University Hospital, Montpellier, France;2. Department of Multidisciplinary Oncology and Therapeutic Innovations, Assistance Publique – Hôpitaux de Marseille, Aix Marseille University, Marseille, France;3. Department of Thoracic Oncology, CHITS CH Sainte Musse, Toulon, France;4. Thoracic Oncology Unit, CHU Grenoble Alpes, Grenoble, France;5. Institut de Cancerologie de Lorraine Alexis Vautrin. 6 Avenue de Bourgogne, Vandoeuvre-les-Nancy, France;6. Pôle Hippocrate, Angers University Hospital, Angers, France;7. Service de Pneumologie, Oncologie Thoracique et soins Intensifs Respiratoires, CHU de Rouen, Rouen, France;8. Service de Pneumologie CHRU Hôpitaux de Tours, Hôpital Bretonneau, Tours, France;9. Service de Pneumologie, CHU Caen Normandie, Caen, France;10. Pôle Médecine, Centre Antoine Lacassagne, Nice, France;11. Department of Thoracic Oncology, Bichat Claude Bernard Hospital, Paris, France;12. Service de Pneumologie, Chu Gabriel-Montpied, Clermont-Ferrand, France;13. Clinique des Cèdres, Château Alliez, Cornebarrieu, France;14. Service de Pneumologie, Centre Hospitalier du Mans, Le Mans, France;15. Service de Pneumologie, Centre Hospitalier de Pau, Pau, France;p. Toulouse University Hospital, Université Paul Sabatier, Toulouse, France;q. Service d’Anatomo-pathologie, Hôpitaux Universitaires Est Parisien Site Tenon, Paris, France;r. Department of Biochemistry, Nantes University Hospital, Nantes, France;s. Department of radiology, Montpellier Regional University Hospital, Montpellier, France;t. Intergroupe Francophone de Cancérologie Thoracique, Paris, France;u. Service de Pneumologie Aiguë Spécialisée et Cancérologie Thoracique, Centre Hospitalier Lyon, Lyon, France |
| |
| Abstract: | IntroductionThis randomized phase II trial aimed at evaluating the engineered programmed cell death ligand 1 (PD-L1) antibody atezolizumab in SCLC progressing after first-line platinum–etoposide chemotherapy.MethodsPatients were randomized 2:1 to atezolizumab (1200 mg intravenously every 3 weeks) until progression or unacceptable toxicity, or conventional chemotherapy (up to 6 cycles of topotecan or re-induction of initial chemotherapy). Patients were not selected based on PD-L1 tissue expression. The primary endpoint was objective response rate at 6 weeks. A two-stage design with 2:1 randomization and O’Brien-Fleming stopping rules was used. The null hypothesis was rejected if more than 12 of 45 patients were responders.ResultsOverall, 73 patients were randomized (atezolizumab n = 49; chemotherapy n = 24). At 6 weeks, 1 of 43 eligible atezolizumab patients achieved an objective response (2.3%, 95% confidence interval CI]: 0.0–6.8), whereas 8 others had stable disease (20.9% disease control rate; 95% CI: 8.8–33.1). Among eligible chemotherapy patients (n = 20), 10% achieved an objective response (65% disease control rate). Median progression-free survival was 1.4 months (95% CI: 1.2–1.5) with atezolizumab and 4.3 months (95% CI: 1.5–5.9) with chemotherapy. Overall survival did not significantly differ between groups. Median overall survival was 9.5 months versus 8.7 months for the atezolizumab and the chemotherapy group, respectively (adjusted hazard ratioatezolizumab : 0.84, 95% CI: 0.45–1.58; p = 0.60). Two atezolizumab patients (4.2%) experienced grade 3 fatigue, and two others grade 1 dysthyroidism. Among 53 evaluable specimens, only 1 (2%) had positive immunohistochemical PD-L1 staining (SP142 clone).ConclusionsAtezolizumab monotherapy in relapsed SCLC failed to show significant efficacy. No unexpected safety concerns were observed. |
| |
| Keywords: | Programmed cell death ligand 1 Atezolizumab Chemotherapy SCLC |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
