title: RECIST progression patterns during EGFR tyrosine kinase inhibitor treatment of advanced non-small cell lung cancer patients harboring an EGFR mutation.
abstract: BACKGROUND
  Progression patterns at the response evaluation criteria in solid tumors-progressive disease (RECIST-PD) during treatment with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) for advanced non-small cell lung cancer (NSCLC) in patients harboring an EGFR mutation are clinically heterogeneous. We evaluated the association between progression patterns during EGFR-TKI treatment and prognosis after treatment in such patients.
  
  
  METHODS
  From 2008 to 2012, 160 consecutive patients with advanced NSCLC harboring an EGFR mutation were treated with EGFR-TKIs (erlotinib or gefitinib). Among these, 104 who experienced RECIST-PD were retrospectively evaluated for initial response to EGFR-TKIs, progression sites, focus of progression (solitary lesion or multiple lesions), symptom status at RECIST-PD evaluation, and post-progression survival (PPS).
  
  
  RESULTS
  Of 104 patients, 96 (92%) had an EGFR major mutation, and 50 (48%) received EGFR-TKIs as first-line treatment. Overall response rate and median time to RECIST-PD on EGFR-TKIs were 68% and 8.2 months, respectively. At the time of attaining RECIST-PD status, 44 (42%) patients were symptomatic, and 60 (58%) were asymptomatic. Progression sites at RECIST-PD were isolated brain in 17 (16%) patients and systemic in 87 (84%): 24 (23%) had a solitary lesion, and 80 (77%) had multiple lesions. After RECIST-PD assessment, 40 (38%) patients continued EGFR-TKIs, and 25 (24%) switched to cytotoxic agents; 10 (10%) received local radiotherapy for an isolated progression site (brain 6; bone 3; lung 1). Median PPS was 10.8 months. Multivariate analysis revealed that asymptomatic or solitary lesion status was associated with significantly longer PPS (asymptomatic: HR 0.36, 95% CI 0.21-0.62, P<0.01; solitary progression lesion: HR 0.45, 95% CI 0.18-99, P=0.04).
  
  
  CONCLUSIONS
  Progression patterns at the RECIST-PD during EGFR-TKI treatment of advanced NSCLC in patients harboring an EGFR mutation are widely diverse, and might be associated with clinical outcome after treatment failure.
authors.affiliation: Department of Thoracic Oncology, National Cancer Center Hospital East, Kashiwa, Chiba, Japan; Department of Thoracic Oncology, Aichi Cancer Center Hospital, Nagoya, Aichi, Japan. Electronic address: t.yoshida@aichi-cc.jp.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Yoshida
authors.affiliation: Department of Thoracic Oncology, National Cancer Center Hospital East, Kashiwa, Chiba, Japan.
authors.forename: Kiyotaka
authors.initials: K
authors.lastname: Yoh
authors.affiliation: Department of Thoracic Oncology, National Cancer Center Hospital East, Kashiwa, Chiba, Japan.
authors.forename: Seiji
authors.initials: S
authors.lastname: Niho
authors.affiliation: Department of Thoracic Oncology, National Cancer Center Hospital East, Kashiwa, Chiba, Japan.
authors.forename: Shigeki
authors.initials: S
authors.lastname: Umemura
authors.affiliation: Department of Thoracic Oncology, National Cancer Center Hospital East, Kashiwa, Chiba, Japan.
authors.forename: Shingo
authors.initials: S
authors.lastname: Matsumoto
authors.affiliation: Department of Thoracic Oncology, National Cancer Center Hospital East, Kashiwa, Chiba, Japan.
authors.forename: Hironobu
authors.initials: H
authors.lastname: Ohmatsu
authors.affiliation: Department of Thoracic Oncology, National Cancer Center Hospital East, Kashiwa, Chiba, Japan; Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan.
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Ohe
authors.affiliation: Department of Thoracic Oncology, National Cancer Center Hospital East, Kashiwa, Chiba, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Goto
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality; D018450:Disease Progression; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000235:genetics*; D005091:Exons; D005260:Female; D000077156:Gefitinib; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009367:Neoplasm Staging; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011799:Quinazolines / Q000627:therapeutic use; D066066:Response Evaluation Criteria in Solid Tumors; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D066246:ErbB Receptors; D000077156:Gefitinib
keywords: EGFR tyrosine kinase inhibitors; Epidermal growth factor receptor mutation; Non-small cell lung cancer