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; Felip, E; Dafni, U; Belka, C; Guckenberger, M; Irigoyen, A; Nadal, E; Becker, Antje; Vees, H; Pless, M; Martinez-Marti, A; Tufman, A; Lambrecht, M; Andratschke, N; Piguet, A C; Kassapian, M; Roschitzki-Voser, H; Rabaglio, Manuela; Stahel, R A; Vansteenkiste, J; ... (2019). 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. Lung cancer, 133, pp. 83-87. Elsevier 10.1016/j.lungcan.2019.05.001

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Clinic of Medical Oncology
04 Faculty of Medicine > Department of Gynaecology, Paediatrics and Endocrinology (DFKE) > Clinic of Paediatric Medicine

UniBE Contributor:

Becker, Antje and Rabaglio, Manuela

Subjects:

600 Technology > 610 Medicine & health

ISSN:

0169-5002

Publisher:

Elsevier

Language:

English

Submitter:

Rebeka Gerber

Date Deposited:

11 Dec 2019 11:39

Last Modified:

11 Dec 2019 11:39

Publisher DOI:

10.1016/j.lungcan.2019.05.001

PubMed ID:

31200833

Uncontrolled Keywords:

Cancer immunotherapy Chemotherapy Combination treatment Immune checkpoint inhibitors NSCLC Nivolumab Non-small cell lung cancer PD-1 inhibitor Radiotherapy

BORIS DOI:

10.7892/boris.134965

URI:

https://boris.unibe.ch/id/eprint/134965

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