Journal article
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.
- Peters S Centre Hospitalier Universitaire Vaudois (CHUV), Département d'Oncologie, Lausanne, Switzerland.
- Felip E Vall d'Hebron University Hospital, Institute of Oncology (VHIO), Barcelona, Spain.
- Dafni U Frontier Science Foundation-Hellas & National and Kapodistrian University of Athens, Greece.
- Belka C Department of Radiation Oncology and DZL Munich, University Hospital, LMU Munich, Germany.
- Guckenberger M University Hospital Zurich, Department for Radiation Oncology, University of Zurich, Switzerland.
- Irigoyen A Hospital Virgen De La Salud, Department of Medical Oncology, Toledo, Spain.
- Nadal E Catalan Institute of Oncology, Department of Medical Oncology, IDIBELL L'Hospitalet, Barcelona, Spain.
- Becker A Amsterdam University Medical Center, Department of Respiratory Diseases, Amsterdam, the Netherlands.
- Vees H Clinic Hirslanden, Radiation Oncology, Zürich, Switzerland.
- Pless M Cantonal Hospital Winterthur, Medical Oncology, Winterthur, Switzerland.
- Martinez-Marti A Vall d'Hebron University Hospital, Institute of Oncology (VHIO), Barcelona, Spain.
- Tufman A Ludwig Maximilian University of Munich (LMU), Medizinische Klinik and Poliklinik V, German Center for Lung Research, Munich, Germany.
- Lambrecht M University Hospitals Gasthuisberg, Department of Radiotherapy-Oncology, Leuven, Belgium.
- Andratschke N University Hospital Zurich, Department for Radiation Oncology, University of Zurich, Switzerland.
- Piguet AC European Thoracic Oncology Platform (ETOP), Bern, Switzerland.
- Kassapian M Frontier Science Foundation-Hellas, Athens, Greece.
- Roschitzki-Voser H European Thoracic Oncology Platform (ETOP), Bern, Switzerland.
- Rabaglio-Poretti M European Thoracic Oncology Platform (ETOP), Bern, Switzerland.
- Stahel RA University Hospital Zurich, Department of Haematology and Oncology, Switzerland.
- Vansteenkiste J University Hospitals Gasthuisberg, Department of Respiratory Diseases, Leuven, Belgium.
- De Ruysscher D Maastro Clinic, Department of Radiation Oncology Maastricht, the Netherlands. Electronic address: dirk.deruysscher@maastro.nl.
- 2019-06-16
Published in:
- Lung cancer (Amsterdam, Netherlands). - 2019
Cancer immunotherapy
Chemotherapy
Combination treatment
Immune checkpoint inhibitors
NSCLC
Nivolumab
Non-small cell lung cancer
PD-1 inhibitor
Radiotherapy
Adult
Aged
Antineoplastic Combined Chemotherapy Protocols
B7-H1 Antigen
Carcinoma, Non-Small-Cell Lung
Chemoradiotherapy
Cohort Studies
Female
Humans
Lung Neoplasms
Male
Middle Aged
Neoplasm Staging
Nivolumab
Platinum Compounds
Programmed Cell Death 1 Receptor
Survival Analysis
Treatment Outcome
English
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.
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.
- Language
-
- English
- Open access status
- closed
- Identifiers
-
- DOI 10.1016/j.lungcan.2019.05.001
- PMID 31200833
- Persistent URL
- https://folia.unifr.ch/global/documents/88652
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