Elsevier

Journal of Thoracic Oncology

Volume 12, Issue 12, December 2017, Pages 1798-1805
Journal of Thoracic Oncology

Original Article
Non–Small Cell Lung Cancer
Early Immune-Related Adverse Events and Association with Outcome in Advanced Non–Small Cell Lung Cancer Patients Treated with Nivolumab: A Prospective Cohort Study

https://doi.org/10.1016/j.jtho.2017.08.022Get rights and content
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Abstract

Introduction

Retrospective studies have shown immune-related adverse events (irAEs) to be associated with better prognosis. However, no prospective clinical trials have been conducted, and little is known regarding the association between irAEs and the outcome of patients with NSCLC after treatment with immunotherapy.

Methods

We conducted a prospective cohort study of patients with advanced NSCLC who were treated with nivolumab between January and December 2016. The association between clinical outcome and irAEs 2 to 6 weeks after commencement of nivolumab treatment was investigated. IrAEs were assessed by at least three independent medical professionals.

Results

A total of 43 patients were enrolled, including 19 patients with irAEs 2 weeks after commencement of nivolumab treatment. Common irAEs included rash, pyrexia, and diarrhea. Programmed cell death ligand 1–positive tumor cell expression was not significantly different between patients with and without irAEs. The objective response and disease control rates were higher in patients with irAEs than in those without irAEs (37% versus 17% and 74% versus 29% [p = 0.17 and p < 0.01], respectively]). Patients with irAEs were associated with a significantly longer median progression-free survival than those without (6.4 months [95% confidence interval: 2.5–not reached] versus 1.5 months [95% confidence interval: 1.2–2.3] [p = 0.01]). These findings were comparable to those for patients with and without irAEs 6 weeks after commencement of nivolumab treatment.

Conclusions

Early irAEs are associated with a better outcome after treatment with immunotherapy. We predicted responses to nivolumab by using early irAEs. Further research is needed to elucidate the mechanisms of these associations.

Keywords

Immune checkpoint inhibitor
Immune-related adverse event
Nivolumab
Non–small cell lung cancer
Programmed cell death ligand 1

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Readers of this article may receive CME credit. Further information can be found at https://www.iaslc.org/journal-based-cme.

Drs. Teraoka and Fujimoto contributed equally to this work.

Disclosure: Dr. Fujimoto reports personal fees from Ono Pharmaceutical Co., Ltd. and Bristol-Myers Squibb K.K. outside the submitted work. The remaining authors declare no conflict of interest.

Trial registration: UMIN000022037.