Solange Peters1, Enriqueta Felip2, Urania Dafni3, Amanda Tufman4, Matthias Guckenberger5, Ruth Álvarez6, Ernest Nadal7, Annemarie Becker8, Hansjörg Vees9, Miklos Pless10, Alex Martinez-Marti2, Maarten Lambrecht11, Nicolaus Andratschke5, Zoi Tsourti12, Anne-Christine Piguet13, Heidi Roschitzki-Voser13, Adrian Gasca-Ruchti13, Johan Vansteenkiste14, Rolf A Stahel15, Dirk De Ruysscher16. 1. Department of Oncology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland. 2. Vall d'Hebron Institute of Oncology, Vall d'Hebron University Hospital, Barcelona, Spain. 3. Frontier Science Foundation-Hellas, Athens, Greece; National and Kapodistrian University of Athens, Athens, Greece. 4. Department of Internal Medicine V, Ludwig-Maximilians University Munich, Munich, Germany; German Center for Lung Research Comprehensive Pneumology Center Munich, Munich, Germany. 5. Department for Radiation Oncology, University Hospital Zurich, University of Zurich, Zurich, Switzerland. 6. Department of Medical Oncology, Hospital Virgen De La Salud, Toledo, Spain. 7. Department of Medical Oncology, Catalan Institute of Oncology, Institut d'Investigació Biomédica de Bellvitge L'Hospitalet, Barcelona, Spain. 8. Department of Respiratory Diseases, Amsterdam University Medical Center, Amsterdam, The Netherlands. 9. Radiation Oncology, Clinic Hirslanden, Zurich, Switzerland. 10. Medical Oncology, Cantonal Hospital Winterthur, Winterthur, Switzerland. 11. Department of Radiotherapy-Oncology, University Hospitals Leuven, Leuven, Belgium. 12. Frontier Science Foundation-Hellas, Athens, Greece. 13. European Thoracic Oncology Platform, Bern, Switzerland. 14. Department of Respiratory Diseases, University Hospital Katholieke Universiteit Leuven, Leuven, Belgium. 15. European Thoracic Oncology Platform, Bern, Switzerland. Electronic address: Rolf.Stahel@etop-eu.org. 16. Department of Radiation Oncology (Maastro), Maastricht University Medical Center, GROW School for Oncology, Maastricht, The Netherlands.
Abstract
INTRODUCTION: The NICOLAS study is the first completed single-arm phase II trial in stage III NSCLC evaluating hierarchically first the safety and then the efficacy of adding nivolumab concurrently to standard definitive concurrent chemoradiotherapy. The safety end point was reported earlier; here, we present the efficacy results. METHODS: Stage IIIA-B unresectable treatment-naive patients with NSCLC received three cycles of platinum-based chemotherapy and concurrent radiotherapy (66 Gy, 33 fractions), along with nivolumab (360 mg, 3-weekly). Nivolumab was continued as monotherapy consolidation for a maximum of 1 year (480 mg, 4-weekly). The primary end point was 1-year progression-free survival (PFS), with a target improvement compared with historical data of at least 15%, from 45% to 60%. To test this efficacy hypothesis, a sample size of 74 assessable patients provided a power of 83% with a one-sided alpha of 5%. RESULTS: A total of 79 patients were enrolled with a median follow-up of 21.0 months (interquartile range: 15.8-25.8 mo) for the primary PFS analysis. A total of 35.4% of the patients had stage IIIA, and 63.3% had stage IIIB disease. The 1-year PFS was 53.7% (95% confidence interval [CI]: 42.0%-64.0%) and the median PFS was 12.7 months (95% CI: 10.1-22.8 mo). Because 37 PFS events occurred in the first year posttreatment among the first 74 assessable patients, a 1-year PFS rate of at least 45% could not be rejected (p = 0.23). At an extended follow-up (median 32.6 mo), 37 deaths have been recorded, with a median overall survival (OS) of 38.8 months (95% CI: 26.8 mo-not estimable) and a 2-year OS rate of 63.7% (95% CI: 51.9%-73.4%). The OS of patients with stage IIIA disease was found to be significantly higher than patients with stage IIIB disease, with a 2-year OS of 81% and 56%, respectively (p = 0.037). CONCLUSIONS: PFS and OS are arithmetically higher in studies involving the same population. However, on the basis of the formal hierarchical efficacy analysis, we could not reject that the 1-year PFS rate is at least 45%.
INTRODUCTION: The NICOLAS study is the first completed single-arm phase II trial in stage III NSCLC evaluating hierarchically first the safety and then the efficacy of adding nivolumab concurrently to standard definitive concurrent chemoradiotherapy. The safety end point was reported earlier; here, we present the efficacy results. METHODS: Stage IIIA-B unresectable treatment-naive patients with NSCLC received three cycles of platinum-based chemotherapy and concurrent radiotherapy (66 Gy, 33 fractions), along with nivolumab (360 mg, 3-weekly). Nivolumab was continued as monotherapy consolidation for a maximum of 1 year (480 mg, 4-weekly). The primary end point was 1-year progression-free survival (PFS), with a target improvement compared with historical data of at least 15%, from 45% to 60%. To test this efficacy hypothesis, a sample size of 74 assessable patients provided a power of 83% with a one-sided alpha of 5%. RESULTS: A total of 79 patients were enrolled with a median follow-up of 21.0 months (interquartile range: 15.8-25.8 mo) for the primary PFS analysis. A total of 35.4% of the patients had stage IIIA, and 63.3% had stage IIIB disease. The 1-year PFS was 53.7% (95% confidence interval [CI]: 42.0%-64.0%) and the median PFS was 12.7 months (95% CI: 10.1-22.8 mo). Because 37 PFS events occurred in the first year posttreatment among the first 74 assessable patients, a 1-year PFS rate of at least 45% could not be rejected (p = 0.23). At an extended follow-up (median 32.6 mo), 37 deaths have been recorded, with a median overall survival (OS) of 38.8 months (95% CI: 26.8 mo-not estimable) and a 2-year OS rate of 63.7% (95% CI: 51.9%-73.4%). The OS of patients with stage IIIA disease was found to be significantly higher than patients with stage IIIB disease, with a 2-year OS of 81% and 56%, respectively (p = 0.037). CONCLUSIONS: PFS and OS are arithmetically higher in studies involving the same population. However, on the basis of the formal hierarchical efficacy analysis, we could not reject that the 1-year PFS rate is at least 45%.
Authors: Jonathan Khalifa; Julien Mazieres; Carlos Gomez-Roca; Maha Ayyoub; Elizabeth Cohen-Jonathan Moyal Journal: Front Oncol Date: 2021-04-21 Impact factor: 6.244