PMID- 31200833 OWN - NLM STAT- MEDLINE DCOM- 20200305 LR - 20200305 IS - 1872-8332 (Electronic) IS - 0169-5002 (Linking) VI - 133 DP - 2019 Jul TI - Safety evaluation of nivolumab added concurrently to radiotherapy in a standard first line chemo-radiotherapy regimen in stage III non-small cell lung cancer-The ETOP NICOLAS trial. PG - 83-87 LID - S0169-5002(19)30441-6 [pii] LID - 10.1016/j.lungcan.2019.05.001 [doi] AB - OBJECTIVES: Chemo-radiotherapy (CRT) and concurrent PD-1 inhibition has shown promising results in pre-clinical models. So far, the feasibility of delivering concurrent CRT and PD-1/PD-L1 inhibition has never been assessed in a clinical trial. MATERIAL AND METHODS: NICOLAS is a phase-II trial evaluating the safety and efficacy of nivolumab combined with CRT in stage III NSCLC. Patients received 3 cycles of platinum-based chemotherapy and concurrent RT (66 Gy/33fractions). Nivolumab started concurrently with RT. The primary endpoint was 6-month post-RT rate of grade->/=3-pneumonitis. A formal interim safety analysis (IA) was scheduled when the first 21 patients reached 3 months follow-up post-RT. An early positive safety conclusion would be reached at IA if there were no grade >/=3-pneumonitis in those patients. Efficacy evaluation was planned provided the safety conclusion was reached. RESULTS AND CONCLUSION: As of 13 December 2018, 82 patients were recruited with median follow-up of 13.4 months. The most frequent adverse events (AEs) were anaemia, fatigue and pneumonitis. No unexpected AEs or increased toxicities were observed. For the first 21 patients, no grade->/=3-pneumonitis was observed by the end of the 3-month post-RT follow-up period. The early safety IA provides evidence that the addition of nivolumab to concurrent CRT is safe and tolerable regarding the 6-month rate of pneumonitis grade >/=3 at the one-sided significance level of 5%. Following that, the 1-year progression-free survival will be evaluated in an expanded patient cohort. NICOLAS trial creates the opportunity for assessing the activity of the combination of checkpoint with concurrent CRT in larger prospective trials for locally advanced NSCLC. CI - Copyright (c) 2019 Elsevier B.V. All rights reserved. FAU - Peters, S AU - Peters S AD - Centre Hospitalier Universitaire Vaudois (CHUV), Departement d'Oncologie, Lausanne, Switzerland. FAU - Felip, E AU - Felip E AD - Vall d'Hebron University Hospital, Institute of Oncology (VHIO), Barcelona, Spain. FAU - Dafni, U AU - Dafni U AD - Frontier Science Foundation-Hellas & National and Kapodistrian University of Athens, Greece. FAU - Belka, C AU - Belka C AD - Department of Radiation Oncology and DZL Munich, University Hospital, LMU Munich, Germany. FAU - Guckenberger, M AU - Guckenberger M AD - University Hospital Zurich, Department for Radiation Oncology, University of Zurich, Switzerland. FAU - Irigoyen, A AU - Irigoyen A AD - Hospital Virgen De La Salud, Department of Medical Oncology, Toledo, Spain. FAU - Nadal, E AU - Nadal E AD - Catalan Institute of Oncology, Department of Medical Oncology, IDIBELL L'Hospitalet, Barcelona, Spain. FAU - Becker, A AU - Becker A AD - Amsterdam University Medical Center, Department of Respiratory Diseases, Amsterdam, the Netherlands. FAU - Vees, H AU - Vees H AD - Clinic Hirslanden, Radiation Oncology, Zurich, Switzerland. FAU - Pless, M AU - Pless M AD - Cantonal Hospital Winterthur, Medical Oncology, Winterthur, Switzerland. FAU - Martinez-Marti, A AU - Martinez-Marti A AD - Vall d'Hebron University Hospital, Institute of Oncology (VHIO), Barcelona, Spain. FAU - Tufman, A AU - Tufman A AD - Ludwig Maximilian University of Munich (LMU), Medizinische Klinik and Poliklinik V, German Center for Lung Research, Munich, Germany. FAU - Lambrecht, M AU - Lambrecht M AD - University Hospitals Gasthuisberg, Department of Radiotherapy-Oncology, Leuven, Belgium. FAU - Andratschke, N AU - Andratschke N AD - University Hospital Zurich, Department for Radiation Oncology, University of Zurich, Switzerland. FAU - Piguet, A C AU - Piguet AC AD - European Thoracic Oncology Platform (ETOP), Bern, Switzerland. FAU - Kassapian, M AU - Kassapian M AD - Frontier Science Foundation-Hellas, Athens, Greece. FAU - Roschitzki-Voser, H AU - Roschitzki-Voser H AD - European Thoracic Oncology Platform (ETOP), Bern, Switzerland. FAU - Rabaglio-Poretti, M AU - Rabaglio-Poretti M AD - European Thoracic Oncology Platform (ETOP), Bern, Switzerland. FAU - Stahel, R A AU - Stahel RA AD - University Hospital Zurich, Department of Haematology and Oncology, Switzerland. FAU - Vansteenkiste, J AU - Vansteenkiste J AD - University Hospitals Gasthuisberg, Department of Respiratory Diseases, Leuven, Belgium. FAU - De Ruysscher, D AU - De Ruysscher D AD - Maastro Clinic, Department of Radiation Oncology Maastricht, the Netherlands. Electronic address: dirk.deruysscher@maastro.nl. LA - eng PT - Clinical Trial, Phase II PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20190503 PL - Ireland TA - Lung Cancer JT - Lung cancer (Amsterdam, Netherlands) JID - 8800805 RN - 0 (B7-H1 Antigen) RN - 0 (CD274 protein, human) RN - 0 (PDCD1 protein, human) RN - 0 (Platinum Compounds) RN - 0 (Programmed Cell Death 1 Receptor) RN - 31YO63LBSN (Nivolumab) SB - IM MH - Adult MH - Aged MH - Antineoplastic Combined Chemotherapy Protocols/*therapeutic use MH - B7-H1 Antigen/antagonists & inhibitors MH - Carcinoma, Non-Small-Cell Lung/*drug therapy/mortality/radiotherapy MH - Chemoradiotherapy MH - Cohort Studies MH - Female MH - Humans MH - Lung Neoplasms/*drug therapy/mortality/radiotherapy MH - Male MH - Middle Aged MH - Neoplasm Staging MH - Nivolumab/*therapeutic use MH - Platinum Compounds/*therapeutic use MH - Programmed Cell Death 1 Receptor/antagonists & inhibitors MH - Survival Analysis MH - Treatment Outcome OTO - NOTNLM OT - Cancer immunotherapy OT - Chemotherapy OT - Combination treatment OT - Immune checkpoint inhibitors OT - NSCLC OT - Nivolumab OT - Non-small cell lung cancer OT - PD-1 inhibitor OT - Radiotherapy EDAT- 2019/06/16 06:00 MHDA- 2020/03/07 06:00 CRDT- 2019/06/16 06:00 PHST- 2019/03/17 00:00 [received] PHST- 2019/04/25 00:00 [revised] PHST- 2019/05/03 00:00 [accepted] PHST- 2019/06/16 06:00 [entrez] PHST- 2019/06/16 06:00 [pubmed] PHST- 2020/03/07 06:00 [medline] AID - S0169-5002(19)30441-6 [pii] AID - 10.1016/j.lungcan.2019.05.001 [doi] PST - ppublish SO - Lung Cancer. 2019 Jul;133:83-87. doi: 10.1016/j.lungcan.2019.05.001. Epub 2019 May 3.