title: Treatments and outcomes of advanced/recurrent non-small cell lung cancer harboring the EGFR T790M mutation: a retrospective observational study of 141 patients in Japan.
abstract: BACKGROUND
  The epidermal growth factor receptor (EGFR) T790M mutation is considered the major mechanism of acquired resistance to EGFR tyrosine kinase inhibitors (EGFR-TKIs) in non-small cell lung cancer (NSCLC) patients with EGFR-sensitizing mutations. Although chemotherapy is commonly used for those patients under the condition without T790M-targeted therapy, the clinical outcomes are poorly defined. Therefore, we aimed to reveal the treatment patterns and clinical outcomes in patients with T790M-positive NSCLC.
  
  
  METHODS
  We conducted a retrospective observational study at 23 sites in Japan, and 141 patients with T790M-positive advanced/recurrent NSCLC were identified from January 2008 to December 2014. Their records were studied to understand treatment patterns after detection of a T790M mutation and to assess the objective response rate (ORR) and median survival time (MST) to specific treatment modalities.
  
  
  RESULTS
  Of 141 patients, 24 had de novo T790M-positive tumors and 117 had acquired T790M-positive tumors, with MSTs (95% CI) of 21.4 (12.4-36.7) and 9.1 (6.4-13.9) months, respectively. The most common regimen was platinum-based doublet chemotherapy ± bevacizumab, which was associated with an ORR/MST of 25.0%/29.1 months, respectively, in patients with de novo T790M mutations, and 22.2%/15.3 months, respectively, in patients with acquired T790M mutations.
  
  
  CONCLUSIONS
  This study reveals the treatment patterns and outcomes of NSCLC patients in Japan after detection of the T790M mutation. The most common treatment following detection of the T790M mutation was platinum-based doublet chemotherapy ± bevacizumab. Platinum-based doublet chemotherapy ± bevacizumab was moderately effective, indicating the need for targeted therapies for patients with T790M mutation-positive NSCLC.
authors.affiliation: Department of Thoracic Oncology, Saitama Cancer Center, Saitama.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Yamane
authors.affiliation: Department of Respiratory Medicine, Saitama Medical University International Medical Center, Saitama.
authors.forename: Ayako
authors.initials: A
authors.lastname: Shiono
authors.affiliation: Department of Pulmonary Medicine and Clinical Immunology, Dokkyo Medical University School of Medicine, Tochigi.
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Ishii
authors.affiliation: Division of Respiratory Medicine, Toho University Omori Medical Center, Tokyo.
authors.forename: Kazutoshi
authors.initials: K
authors.lastname: Isobe
authors.affiliation: Department of Respiratory Medicine, Tohoku University Hospital, Miyagi.
authors.forename: Eisaku
authors.initials: E
authors.lastname: Miyauchi
authors.affiliation: Department of Respiratory Medicine, Respiratory Center, Toranomon Hospital, Tokyo.
authors.forename: Kazuma
authors.initials: K
authors.lastname: Kishi
authors.affiliation: Division of Pulmonary Medicine, Department of Medicine, Keio University School of Medicine, Tokyo.
authors.forename: Makoto
authors.initials: M
authors.lastname: Nishino
authors.affiliation: Department of Pulmonary Medicine, Sendai Kousei Hospital, Miyagi.
authors.forename: Shunichi
authors.initials: S
authors.lastname: Sugawara
authors.affiliation: Department of Respiratory Medicine, Juntendo University Graduate School of Medicine, Tokyo.
authors.forename: Ryo
authors.initials: R
authors.lastname: Ko
authors.affiliation: Division of Pulmonary Medicine, Clinical Department of Internal Medicine, Jichi Medical University Saitama Medical Center, Saitama.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Koyama
authors.affiliation: AstraZeneca K.K. , Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Yabuki
authors.affiliation: Department of Respiratory Medicine, Saitama Medical University International Medical Center, Saitama kobakuni@saitama-med.ac.jp.
authors.forename: Kunihiko
authors.initials: K
authors.lastname: Kobayashi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000068258:Bevacizumab / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D004359:Drug Therapy, Combination; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D006801:Humans; D007564:Japan; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009364:Neoplasm Recurrence, Local; D012189:Retrospective Studies; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D000068258:Bevacizumab; C512478:EGFR protein, human; D066246:ErbB Receptors
keywords: T790M mutation; epidermal growth factor receptor; non-small-cell lung cancer; retrospective studies; treatment outcome