Jean-Louis Pujol1, Laurent Greillier2, Clarisse Audigier-Valette3, Denis Moro-Sibilot4, Lionel Uwer5, José Hureaux6, Florian Guisier7, Delphine Carmier8, Jeannick Madelaine9, Josiane Otto10, Valérie Gounant11, Patrick Merle12, Pierre Mourlanette13, Olivier Molinier14, Aldo Renault15, Audrey Rabeau16, Martine Antoine17, Marc G Denis18, Sebastien Bommart19, Alexandra Langlais20, Franck Morin20, Pierre-Jean Souquet21. 1. Department of Thoracic Oncology, Montpellier Regional University Hospital, Montpellier, France. Electronic address: jl-pujol@chu-montpellier.fr. 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. 16. Toulouse University Hospital, Université Paul Sabatier, Toulouse, France. 17. Service d'Anatomo-pathologie, Hôpitaux Universitaires Est Parisien Site Tenon, Paris, France. 18. Department of Biochemistry, Nantes University Hospital, Nantes, France. 19. Department of radiology, Montpellier Regional University Hospital, Montpellier, France. 20. Intergroupe Francophone de Cancérologie Thoracique, Paris, France. 21. Service de Pneumologie Aiguë Spécialisée et Cancérologie Thoracique, Centre Hospitalier Lyon, Lyon, France.
Abstract
INTRODUCTION: This 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. METHODS: Patients 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. RESULTS: Overall, 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). CONCLUSIONS:Atezolizumab monotherapy in relapsed SCLC failed to show significant efficacy. No unexpected safety concerns were observed.
RCT Entities:
INTRODUCTION: This 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. METHODS:Patients 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. RESULTS: Overall, 73 patients were randomized (atezolizumab n = 49; chemotherapy n = 24). At 6 weeks, 1 of 43 eligible atezolizumabpatients 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 atezolizumabpatients (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). CONCLUSIONS:Atezolizumab monotherapy in relapsed SCLC failed to show significant efficacy. No unexpected safety concerns were observed.
Authors: Erin L Schenk; Sumithra J Mandrekar; Grace K Dy; Marie Christine Aubry; Angelina D Tan; Shaker R Dakhil; Bradley A Sachs; Jorge J Nieva; Erin Bertino; Christine Lee Hann; Steven E Schild; Troy W Wadsworth; Alex A Adjei; Julian R Molina Journal: J Thorac Oncol Date: 2019-10-09 Impact factor: 15.609
Authors: Diego L Kaen; Nicolas Minatta; Alessandro Russo; Umberto Malapelle; Diego de Miguel-Pérez; Christian Rolfo Journal: Adv Exp Med Biol Date: 2021 Impact factor: 2.622
Authors: Zhicheng Niu; Shenghu Guo; Jing Cao; Yuehua Zhang; Xiaojin Guo; Francesco Grossi; Yoshinobu Ichiki; You Li; Zhiyu Wang Journal: Ann Transl Med Date: 2021-04
Authors: Roberto Ferrara; Diego Signorelli; Claudia Proto; Arsela Prelaj; Marina Chiara Garassino; Giuseppe Lo Russo Journal: Transl Lung Cancer Res Date: 2021-06