title: Clinical characteristics of non-small cell lung cancer patients who experienced acquired resistance during gefitinib treatment.
abstract: BACKGROUND
  The NSCLC patients who experienced good clinical responses to an EGFR-TKI will inevitably develop acquired resistance. A great deal of research is being carried out to discover the molecular mechanisms underlying this resistance. In comparison, few studies have been conducted to find out about the clinical characteristics of acquired resistance in the patients who had responded to an EGFR-TKI. Herein we investigated clinical characteristics of NSCLC patients who experienced acquired resistance during gefitinib therapy.
  
  
  METHODS
  We reviewed NSCLC patients who showed a clinical benefit from initial gefitinib therapy. All clinical data were obtained from 11 centers of Korean Molecular Lung Cancer Group (KMLCG). The clinical manifestations of acquired resistance, time to progression (TTP), and post-progression survival (PPS) after gefitinib failure were analyzed retrospectively.
  
  
  RESULTS
  A total of 417 patients were recruited. Median TTP was 10.2 months (95% CI, 9.5-10.9). TTP showed a significant longer duration in female, non-smoker, and patients with adenocarcinoma. At the time of acquired resistance, 63.3% of the patients showed symptomatic deterioration. Sites of disease progression were as follows: primary lung lesion in 58.4%, previous metastasis in 38.3%, and new metastasis in 54.2%. Patients with EGFR wild type showed a tendency of higher frequency in symptomatic deterioration and newly development of CNS metastasis compared with patients with EGFR mutation. There was a significant difference in newly development of lung metastasis between patients with exon 19 deletion and those with L858R mutation (41.4% vs. 6.3%, p=0.02). PPS was 8.9 months (95% CI, 7.4-10.4). Smoking history, PS, new CNS lesion and subsequent chemotherapy were independent factors for PPS.
  
  
  CONCLUSIONS
  This study suggests that clinical manifestations of acquired resistance may be different according to EGFR mutation status and EGFR mutation genotype. In addition, subsequent chemotherapy confers clinical benefit in terms of PPS in NSCLC patients who experienced acquired resistance after gefitinib therapy.
authors.affiliation: Department of Internal Medicine, Korea Cancer Center Hospital, 215-4, Gongneung-dong, Nowon-gu, Seoul 139-706, Republic of Korea.
authors.forename: Hye-Ryoun
authors.initials: HR
authors.lastname: Kim
authors.affiliation: Department of Oncology, Asan Medical Center, Ulsan University College of Medicine, Seoul, Republic of Korea.
authors.forename: Jae Chol
authors.initials: JC
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Chonnam National University College of Medicine, Hwasun Hospital, Hwasun, Republic of Korea.
authors.forename: Young-Chul
authors.initials: YC
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Chonnam National University College of Medicine, Hwasun Hospital, Hwasun, Republic of Korea.
authors.forename: Kyu-Sik
authors.initials: KS
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Chonnam National University College of Medicine, Hwasun Hospital, Hwasun, Republic of Korea.
authors.forename: In-Jae
authors.initials: IJ
authors.lastname: Oh
authors.affiliation: Department of Internal Medicine, Guro Hospital, Korea University College of Medicine, Seoul, Republic of Korea.
authors.forename: Sung Yong
authors.initials: SY
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Kosin University College of Medicine, Pusan, Republic of Korea.
authors.forename: Tae Won
authors.initials: TW
authors.lastname: Jang
authors.affiliation: Department of Internal Medicine, Pusan National University College of Medicine, Pusan, Republic of Korea.
authors.forename: Min Ki
authors.initials: MK
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Yeungnam University College of Medicine, Daegu, Republic of Korea.
authors.forename: Kyeong-Cheol
authors.initials: KC
authors.lastname: Shin
authors.affiliation: Department of Internal Medicine, Yeungnam University College of Medicine, Daegu, Republic of Korea.
authors.forename: Gwan Ho
authors.initials: GH
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Inha University College of Medicine, Incheon, Republic of Korea.
authors.forename: Jeong-Seon
authors.initials: JS
authors.lastname: Ryu
authors.affiliation: Department of Internal Medicine, Hallym University College of Medicine, Anyang, Republic of Korea.
authors.forename: Seung Hoon
authors.initials: SH
authors.lastname: Jang
authors.affiliation: Department of Internal Medicine, Konyang University College of Medicine, Daejeon, Republic of Korea.
authors.forename: Ji Woong
authors.initials: JW
authors.lastname: Son
authors.affiliation: Department of Internal Medicine, Chungnam National University College of Medicine, Deajeon, Republic of Korea.
authors.forename: Jeong Eun
authors.initials: JE
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Chungnam National University College of Medicine, Deajeon, Republic of Korea.
authors.forename: Sun Young
authors.initials: SY
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Konkuk University College of Medicine, Seoul, Republic of Korea.
authors.forename: Hee Joung
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Konkuk University College of Medicine, Seoul, Republic of Korea. Electronic address: kyleemd@kuh.ac.kr.
authors.forename: Kye Young
authors.initials: KY
authors.lastname: Lee
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D016543:Central Nervous System Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics*; D005260:Female; D000077156:Gefitinib; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009367:Neoplasm Staging; D011799:Quinazolines / Q000008:administration & dosage* / Q000009:adverse effects; D012189:Retrospective Studies; D012307:Risk Factors; D012737:Sex Factors; D016019:Survival Analysis
chemical_list: D011799:Quinazolines; C512478:EGFR protein, human; D066246:ErbB Receptors; D000077156:Gefitinib
keywords: Acquired resistance; EGFR-tyrosine kinase inhibitor; Failure togefitinib; Gefitinib; Non-small cell lung cancer; Post-progression survival (PPS)