title: Development of a skin rash within the first week and the therapeutic effect in afatinib monotherapy for EGFR-mutant non-small cell lung cancer (NSCLC): Okayama Lung Cancer Study Group experience.
abstract: Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are now key agents in treating EGFR-mutant non-small cell lung cancer (NSCLC). The efficacy of gefitinib or erlotinib monotherapy can be predicted by the development of a skin rash. However, it has not been fully evaluated if this is the case with afatinib monotherapy.
  
  
  
  We retrospectively studied 49 consecutive patients with EGFR-mutant NSCLC who received afatinib therapy between 2009 and 2015. The relationship of several toxicities with tumor response was examined.
  
  
  
  Grade 2, or more severe, common adverse events (AEs) included skin rash in 17 patients (35 %), diarrhea in 19 (39 %) and mucositis in 15 (31 %). Of these, the number of patients who developed ≥Grade 2 AEs during the first week after the initiation of afatinib therapy was: five patients had skin rash (10 %), 12 patients had diarrhea (25 %) and four patients had mucositis (8 %). As for an objective response, 21 (43 %) of the 49 had a partial response. Associating the AEs with the antitumor effect, those who had a ≥Grade 2 skin rash within the first week tended to have a greater tumor response compared with those without a rash (80 vs. 39 %; p = 0.077).
  
  
  
  Our small study demonstrated that the early development of a skin rash might be associated with the response to afatinib monotherapy.
authors.affiliation: Department of Respiratory Medicine, Okayama University Hospital, Okayama, Japan.
authors.forename: Kenichiro
authors.initials: K
authors.lastname: Kudo
authors.affiliation: Department of Respiratory Medicine, Okayama University Hospital, Okayama, Japan. khotta@okayama-u.ac.jp.|Department of Hematology and Oncology, Okayama University Hospital, 2-5-1, Shikatacho, Kitaku, Okayama, 700-8558, Japan. khotta@okayama-u.ac.jp.
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Hotta
authors.affiliation: Department of Respiratory Medicine, Japanese Red Cross Okayama Hospital, Okayama, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Bessho
authors.affiliation: Department of Thoracic Oncology and Medicine, NHO Shikoku Cancer Center, Matsuyama, Japan.
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Nogami
authors.affiliation: Department of Thoracic Oncology and Medicine, NHO Shikoku Cancer Center, Matsuyama, Japan.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Kozuki
authors.affiliation: Department of Respiratory Medicine, NHO Iwakuni Medical Center, Iwakuni, Japan.
authors.forename: Shoichi
authors.initials: S
authors.lastname: Kuyama
authors.affiliation: Department of Respiratory Medicine, Ehime Prefectural Central Hospital, Matsuyama, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Inoue
authors.affiliation: Department of Respiratory Medicine, Chugoku Central Hospital, Fukuyama, Japan.
authors.forename: Shingo
authors.initials: S
authors.lastname: Harita
authors.affiliation: Department of Respiratory Medicine, Chugoku Central Hospital, Fukuyama, Japan.
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Okada
authors.affiliation: Department of Respiratory Medicine, NHO Fukuyama Medical Center, Fukuyama, Japan.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Gemba
authors.affiliation: Department of Respiratory Medicine, Japanese Red Cross Kobe Hospital, Kobe, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Fujii
authors.affiliation: Department of General Internal Medicine 4, Kawasaki Medical School, Okayama, Japan.
authors.forename: Nagio
authors.initials: N
authors.lastname: Takigawa
authors.affiliation: Department of Respiratory Medicine, Okayama University Hospital, Okayama, Japan.
authors.forename: Naohiro
authors.initials: N
authors.lastname: Oda
authors.affiliation: Department of Hematology and Oncology, Okayama University Hospital, 2-5-1, Shikatacho, Kitaku, Okayama, 700-8558, Japan.
authors.forename: Mitsune
authors.initials: M
authors.lastname: Tanimoto
authors.affiliation: Department of Respiratory Medicine, Okayama University Hospital, Okayama, Japan.
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Kiura
mesh_terms: D000328:Adult; D000077716:Afatinib; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D002173:Cancer Care Facilities; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D066246:ErbB Receptors / Q000235:genetics*; D005076:Exanthema / Q000139:chemically induced*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011799:Quinazolines / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D012189:Retrospective Studies; D013997:Time Factors
chemical_list: D000970:Antineoplastic Agents; D011799:Quinazolines; D000077716:Afatinib; C512478:EGFR protein, human; D066246:ErbB Receptors
keywords: Afatinib; Lung cancer; Response; Skin rash