title: Clinical features and risk factors of panitumumab-induced interstitial lung disease: a postmarketing all-case surveillance study.
abstract: BACKGROUND
  Drug-induced interstitial lung disease (ILD) is one of the most serious adverse reactions associated with the molecularly targeted drugs. Panitumumab has been approved for advanced or recurrent colorectal cancer. Although there were no adverse reaction reports of ILD in panitumumab monotherapy, 4 cases in combination chemotherapy were reported prior to its approval in Japan in 2010. Several studies also reported that the incidence of drug-induced ILD was higher in Japan than in other countries. The clinical features of ILD and the associated risk factors therefore need investigation.
  
  
  METHODS
  We analyzed the data from 3085 unresectable, advanced or recurrent colorectal cancer patients enrolled in a postmarketing all-case surveillance study of panitumumab in Japan. ILD case reports were assessed based on the clinical and radiologic findings by a committee of external experts. Multivariate analysis using Cox's hazard model identified the risk factors.
  
  
  RESULTS
  ILD incidence (1.3 %) and mortality rates (51.3 %) were similar to those of patients receiving another anti-epidermal growth factor receptor (EGFR) monoclonal antibody in Japan. No specific onset timing was determined. Although panitumumab-specific ILD findings were not observed in computed tomography images or clinical practice, panitumumab can induce ILD with diffuse alveolar damage, as do the other anti-EGFR targeting drugs. A history/complication of ILD, male sex, poor general condition, and 65 years or older were identified as ILD risk factors, and no history of previous drug treatment was an apparent risk factor.
  
  
  CONCLUSIONS
  Panitumumab-induced ILD can occur at any time after initiation, and close and regular monitoring is needed.
authors.affiliation: Pharmacovigilance Department, Takeda Pharmaceutical Company Limited, 4-9, Hiranomachi 2-chome, Chuo-ku, Osaka, 541-0046, Japan. Vectibix_TakedaSafety@takeda.co.jp.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Osawa
authors.affiliation: Fukujuji Hospital, Kiyose, Japan.|Japan Anti-Tuberculosis Association, Tokyo, Japan.
authors.forename: Shoji
authors.initials: S
authors.lastname: Kudoh
authors.affiliation: Department of Diagnostic Radiology, Saitama International Medical Center, Saitama Medical University, Hidaka, Japan.
authors.forename: Fumikazu
authors.initials: F
authors.lastname: Sakai
authors.affiliation: Division of Diagnostic Radiology, Shizuoka Cancer Center, Nagaizumi-Cho, Shizuoka, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Endo
authors.affiliation: Department of Gastrointestinal Medical Oncology, National Cancer Center Hospital, Tokyo, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Hamaguchi
authors.affiliation: Pharmacovigilance Department, Takeda Pharmaceutical Company Limited, 4-9, Hiranomachi 2-chome, Chuo-ku, Osaka, 541-0046, Japan.
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Ogino
authors.affiliation: Pharmacovigilance Department, Takeda Pharmaceutical Company Limited, 4-9, Hiranomachi 2-chome, Chuo-ku, Osaka, 541-0046, Japan.
authors.forename: Miyo
authors.initials: M
authors.lastname: Yoneoka
authors.affiliation: Pharmacovigilance Department, Takeda Pharmaceutical Company Limited, 4-9, Hiranomachi 2-chome, Chuo-ku, Osaka, 541-0046, Japan.
authors.forename: Motonobu
authors.initials: M
authors.lastname: Sakaguchi
authors.affiliation: Pharmacovigilance Department, Takeda Pharmaceutical Company Limited, 4-9, Hiranomachi 2-chome, Chuo-ku, Osaka, 541-0046, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nishimoto
authors.affiliation: Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan.
authors.forename: Akihiko
authors.initials: A
authors.lastname: Gemma
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000009:adverse effects*; D000970:Antineoplastic Agents / Q000009:adverse effects*; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000378:metabolism; D005260:Female; D006304:Health Status; D006801:Humans; D015994:Incidence; D007564:Japan / Q000453:epidemiology; D017563:Lung Diseases, Interstitial / Q000139:chemically induced* / Q000000981:diagnostic imaging / Q000453:epidemiology*; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D000077544:Panitumumab; D011358:Product Surveillance, Postmarketing; D016016:Proportional Hazards Models; D012307:Risk Factors; D012737:Sex Factors; D014057:Tomography, X-Ray Computed; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D000077544:Panitumumab; C512478:EGFR protein, human; D066246:ErbB Receptors
keywords: Colorectal cancer; Interstitial lung disease; Panitumumab; Postmarketing surveillance; Risk factors