title: Nivolumab-induced interstitial lung disease analysis of two phase II studies patients with recurrent or advanced non-small-cell lung cancer.
abstract: Drug-induced interstitial lung disease (ILD) is often associated with high mortality; however it is difficult to predict and manage. we examined the clinical findings and imaging characteristics of nivolumab induced ILD reported in the two phase II studies patients with recurrent or advanced non-small-cell lung cancer.
  
  
  
  We examined the clinical findings and imaging characteristics of all cases of ILD reported in two phase II trials of nivolumab, an anti-programmed death-1 antibody, in Japanese patients with recurrent or advanced non-small-cell lung cancer. These studies are registered with the Japan Pharmaceutical Information Center, numbers JapicCTI-132072, JapicCTI-132073.
  
  
  
  Eight (7.2%; two with squamous cell carcinoma, six with non-squamous cell carcinoma) of the 111 patients included in these two studies experienced ILD, and a causal relationship with nivolumab could not be ruled out in any of them. ILD of ≥grade 3 severity was found in four patients (3.6%), and ILD was considered a serious treatment-related adverse event in seven patients (6.3%). All of the patients who experienced ILD were male and had a history of smoking, with a median age of 65 years (range 52-78 years). In seven of the eight patients who experienced ILD, their events were rapidly resolving or resolved spontaneously or with steroid therapy; one patient died of respiratory failure without resolution of ILD, after docetaxel treatment was initiated following nivolumab discontinuation. Chest computed tomography images for the seven patients with resolving or resolution of ILD showed a pattern of organizing pneumonia or nonspecific interstitial pneumonia without traction bronchiectasis, while the patient who died had traction bronchiectasis.
  
  
  
  Although the risk factors for nivolumab-induced ILD were not identified, careful monitoring including imaging examinations is important in preventing the worsening of ILD in patients receiving nivolumab.
authors.affiliation: Kanagawa Cancer Center, Kanagawa, Japan. Electronic address: katote@kcch.jp.
authors.forename: Terufumi
authors.initials: T
authors.lastname: Kato
authors.affiliation: Kitasato University Hospital, Kanagawa, Japan.
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Masuda
authors.affiliation: Kyushu University Hospital, Fukuoka, Japan.
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Nakanishi
authors.affiliation: Yamazaki Hospital, Shiga, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Takahashi
authors.affiliation: Aichi Cancer Center Hospital, Aichi, Japan.
authors.forename: Toyoaki
authors.initials: T
authors.lastname: Hida
authors.affiliation: Saitama Cancer Center, Saitama, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sakai
authors.affiliation: Kinki-chuo Chest Medical Center, Osaka, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Atagi
authors.affiliation: Institute of Biomedical Research and Innovation, Hyogo, Japan.
authors.forename: Shiro
authors.initials: S
authors.lastname: Fujita
authors.affiliation: Niigata Cancer Center Hospital, Niigata, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Tanaka
authors.affiliation: Osaka City General Hospital, Osaka, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Takeda
authors.affiliation: Hyogo Cancer Center, Hyogo, Japan.
authors.forename: Miyako
authors.initials: M
authors.lastname: Satouchi
authors.affiliation: ONO Pharmaceutical Co., Ltd., Osaka, Japan.
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Namba
authors.affiliation: St. Luke's International Hospital, Tokyo, Japan.
authors.forename: Tomohide
authors.initials: T
authors.lastname: Tamura
mesh_terms: D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects* / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000494:pharmacology; D002289:Carcinoma, Non-Small-Cell Lung / Q000150:complications* / Q000188:drug therapy / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000150:complications* / Q000188:drug therapy / Q000473:pathology; D018450:Disease Progression; D000077143:Docetaxel; D005260:Female; D006801:Humans; D007564:Japan / Q000453:epidemiology; D017563:Lung Diseases, Interstitial / Q000139:chemically induced* / Q000000981:diagnostic imaging / Q000401:mortality / Q000473:pathology; D008175:Lung Neoplasms / Q000150:complications* / Q000188:drug therapy / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000150:complications* / Q000188:drug therapy / Q000473:pathology; D009367:Neoplasm Staging; D000077594:Nivolumab; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects; D043823:Taxoids / Q000494:pharmacology; D014057:Tomography, X-Ray Computed; D050257:Tubulin Modulators / Q000494:pharmacology
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D043823:Taxoids; D050257:Tubulin Modulators; D000077143:Docetaxel; D000077594:Nivolumab
keywords: Chest image; Drug-induced lung injury; Interstitial lung disease; Nivolumab; Non-small-cell lung cancer