title: First-Line Erlotinib Therapy Until and Beyond Response Evaluation Criteria in Solid Tumors Progression in Asian Patients With Epidermal Growth Factor Receptor Mutation-Positive Non-Small-Cell Lung Cancer: The ASPIRATION Study.
abstract: OBJECTIVE
  Continuing molecularly targeted treatment beyond disease progression in non-small-cell lung cancer (NSCLC) has appeared promising in retrospective analyses, highlighting the challenge to identify whether progression is the optimal time to switch treatment.
  
  
  OBJECTIVE
  To study the efficacy of first-line erlotinib therapy in patients with NSCLC with activating EGFR mutations and postprogression erlotinib therapy.
  
  
  METHODS
  ASPIRATION (Asian Pacific trial of Tarceva as first-line in EGFR mutation) was a phase 2, open-label, single-arm study conducted from 2011 to 2012 in 23 centers in Hong Kong, Korea, Taiwan, and Thailand of adults with stage IV, EGFR mutation-positive NSCLC, with ECOG performance status 0 to 2.
  
  
  METHODS
  Patients received erlotinib 150 mg/d orally until disease progression, after which erlotinib therapy could be continued at patient and/or investigator discretion.
  
  
  METHODS
  The primary end point was progression-free survival (PFS1; time to Response Evaluation Criteria in Solid Tumours 1.1 progression or death). Secondary end points included PFS2 (time to off-erlotinib progression if erlotinib therapy was extended beyond progression at patient and/or investigator discretion), objective response rate, disease control rate, overall survival, and safety. The use of plasma-based assessment of EGFR mutations was also investigated.
  
  
  RESULTS
  Of 359 patients screened, 208 were enrolled. Median follow-up was 11.3 (95% CI, 10.9-13.0) months. Of the 207 intent-to-treat patients (62.3% female; median age, 60.8 [range, 28-89] y), 176 had a PFS1 event (171 progression and 5 deaths); of these, 78 discontinued and 93 continued erlotinib therapy following progression. Median PFS1 was 10.8 (95% CI, 9.2-11.1) months. Median PFS1 and PFS2 in the 93 continuing patients was 11.0 (95% CI, 9.2-11.1) and 14.1 (95% CI, 12.2-15.9) months, respectively. Median PFS1 and PFS2 was 11.0 (95% CI, 9.3-12.0) and 14.9 (95% CI, 12.2-17.2) months in patients with exon 19 deletions or L585R mutations. Overall response rate was 66.2%; disease control rate was 82.6%. Median overall survival was 31.0 months (95% CI, 27.3 months to not reached). In the safety population (n = 207) serious adverse events were reported in 27.1%, with events of at least grade 3 experienced by 50.2%. Sensitivity and specificity of plasma-based EGFR mutation analysis was 77% and 92%, respectively.
  
  
  CONCLUSIONS
  ASPIRATION supports the efficacy of first-line erlotinib therapy in patients with EGFR mutation-positive NSCLC and that treatment beyond progression is feasible and may delay salvage therapy in selected patients.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT01310036.
authors.affiliation: Division of Haematology-Oncology, Samsung Medical Centre, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Keunchil
authors.initials: K
authors.lastname: Park
authors.affiliation: Department of Internal Medicine, National Taiwan University Hospital, Taipei City, Taiwan.
authors.forename: Chong-Jen
authors.initials: CJ
authors.lastname: Yu
authors.affiliation: Department of Oncology, Asan Medical Centre, University of Ulsan College of Medicine, Seoul, South Korea.
authors.forename: Sang-We
authors.initials: SW
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung City, Taiwan 5Chang Gung University College of Medicine, Kaohsiung City, Taiwan.
authors.forename: Meng-Chih
authors.initials: MC
authors.lastname: Lin
authors.affiliation: Division of Medical Oncology, Chulalongkorn University, Bangkok, Thailand.
authors.forename: Virote
authors.initials: V
authors.lastname: Sriuranpong
authors.affiliation: Department of Chest Medicine, Taipei Veteran General Hospital, Taipei, Taiwan8School of Medicine, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Chun-Ming
authors.initials: CM
authors.lastname: Tsai
authors.affiliation: Department of Haematology and Medical Oncology, Seoul National University Bundang Hospital, Bundang, Korea.
authors.forename: Jong-Seok
authors.initials: JS
authors.lastname: Lee
authors.affiliation: Seoul St Mary's Hospital, Seoul, Korea.
authors.forename: Jin-Hyoung
authors.initials: JH
authors.lastname: Kang
authors.affiliation: Department of Chemical Pathology, Chinese University of Hong Kong, Hong Kong.
authors.forename: K C Allen
authors.initials: KC
authors.lastname: Chan
authors.affiliation: F. Hoffmann-La Roche Ltd, Basel, Switzerland.
authors.forename: Pablo
authors.initials: P
authors.lastname: Perez-Moreno
authors.affiliation: Roche Products Pty Ltd, Dee Why, Australia.
authors.forename: Peter
authors.initials: P
authors.lastname: Button
authors.affiliation: Division of Haematology-Oncology, Samsung Medical Centre, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Myung-Ju
authors.initials: MJ
authors.lastname: Ahn
authors.affiliation: State Key Laboratory of South China, Hong Kong Cancer Institute, Chinese University of Hong Kong, Sha Tin, Hong Kong.
authors.forename: Tony
authors.initials: T
authors.lastname: Mok
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D044466:Asian People; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics*; D000069347:Erlotinib Hydrochloride / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use; D066066:Response Evaluation Criteria in Solid Tumors
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D000069347:Erlotinib Hydrochloride; C512478:EGFR protein, human; D066246:ErbB Receptors