Nivolumab-induced interstitial lung disease (ILD) in Japanese patients with non-small cell lung cancer: A study on risk factors for fatal outcome.

Authors

Terufumi Kato

Terufumi Kato

Kanagawa Cancer Center, Yokohama, Japan

Terufumi Kato , Fumikazu Sakai , Tomohisa Baba , Masahiko Kusumoto , Hirotsugu Kenmotsu , Hiroaki Sugiura , Junya Tominaga , Katsunori Oikado , Masafumi Sata , Masahiro Endo , Noriyo Yanagawa , Shinichi Sasaki , Tae Iwasawa , Yoshinobu Saito , Yutaka Fujiwara , Yuichiro Ohe , Yoshihiko Ito , Yasuhiro Tahara , Kazuyoshi Kuwano

Organizations

Kanagawa Cancer Center, Yokohama, Japan, Saitama Medical University International Medical Center, Hidaka, Japan, Kanagawa Cardiovascular and Respiratory Center, Yokohama, Japan, National Cancer Center Hospital East, Kashiwa, Japan, Division of Thoracic Oncology, Shizuoka Cancer Center, Shizuoka, Japan, Keio University School of Medicine, Tokyo, Japan, Tohoku University School of Medicine, Sendai, Japan, Department of Diagnostic Imaging, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan, Division of Diagnostic Radiology, Shizuoka Cancer Center, Shizuoka, Japan, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan, Juntendo University Urayasu Hospital, Chiba, Japan, Nippon Medical School Hospital, Tokyo, Japan, Department of Thoracic Oncology, National Cancer Center Hospital East, Tokyo, Japan, Pharmacovigilance Division, ONO Pharmaceutical Co., Ltd, Osaka, Japan, The Jikei University School of Medicine, Tokyo, Japan

Research Funding

Pharmaceutical/Biotech Company

Background: We investigated case reports of nivolumab-induced ILD in patients with non-small cell lung cancer to identify risk factors for poor prognosis of ILD. Methods: Among data obtained during post-marketing surveillance of nivolumab, case reports of ILD with detailed clinical course and chest imaging (CT) findings were assessed by the ILD Expert Review Committee, which consists of respiratory medicine specialists and expert chest radiologists. The imaging findings were examined and classified into those with typical or atypical patterns. Atypical patterns included shadows limited to surrounding tumors designated as “peritumoral infiltration”, relapse of radiation pneumonitis, worsening of underlying infection, and predominant shadow in diseased side. CT pattern was classified as DAD (diffuse alveolar damage) or non-DAD. Data were analyzed using a multivariate stepwise logistic regression analysis. Results: Among 160 reported cases of ILD, 140 cases were considered to be induced by nivolumab. Imaging findings showed typical patterns in 92 patients, and 23 (25.0%) died of ILD. Atypical patterns were noted in 48 patients, and 5 (10.4%) died of ILD. The following table summarizes the results of univariate and multivariate analyses of risk factors for poor prognosis of ILD. See table. DAD pattern was observed in 20, 14 (70%) among them showed fatal outcome, whereas non-DAD pattern showed it in 14/120 (11.7%). Male and pretreatment CRP level were significant risk factors for fatal outcome. Conclusions: Nivolumab-induced ILD may show some atypical pattern that was not seen in conventional chemotherapy or EGFR-TKI. Outcome of patients with atypical patterns was better than those with typical patterns. DAD pattern at CT, male, and pretreatment level of CRP were identified as risk factors of fatal outcome.

FactorsCategoryNDeath due to ILDUnivariate analysisMultivariate
analysis
N (%)Odds ratio
[95% confidence interval]
P value
GenderMale11725 ( 21.4)1.80.0135
Female233 ( 13.0)[0.5, 6.6]
ILD image patternDAD pattern2014 ( 70.0)17.7<0.0001
Non-DAD pattern12014 ( 11.7)[5.8, 53.4]
Baseline CRP (mg/dL)<57813 ( 16.7)2.80.0162
≥53111 ( 35.5)[1.1, 7.1]

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Abstract Details

Meeting

2017 ASCO Annual Meeting

Session Type

Poster Session

Session Title

Lung Cancer—Non-Small Cell Metastatic

Track

Lung Cancer

Sub Track

Metastatic Non–Small Cell Lung Cancer

Citation

J Clin Oncol 35, 2017 (suppl; abstr 9077)

DOI

10.1200/JCO.2017.35.15_suppl.9077

Abstract #

9077

Poster Bd #

403

Abstract Disclosures