title: First-Line Pemetrexed plus Cisplatin followed by Gefitinib Maintenance Therapy versus Gefitinib Monotherapy in East Asian Never-Smoker Patients with Locally Advanced or Metastatic Nonsquamous Non-Small Cell Lung Cancer: Final Overall Survival Results from a Randomized Phase 3 Study.
abstract: BACKGROUND
  The primary analysis of this open-label, randomized, multicenter phase 3 study revealed no significant difference in progression-free survival between pemetrexed plus cisplatin followed by maintenance gefitinib (PC/G) and gefitinib monotherapy (G) in patients with advanced nonsquamous non-small cell lung cancer (NSCLC) and unknown epidermal growth factor receptor gene (EGFR) mutation status; however, the hazard ratio favored PC/G. This report describes the final overall survival (OS) results.
  
  
  METHODS
  Chemonaive, East Asian light ex-smokers/never-smokers with advanced nonsquamous NSCLC and unknown EGFR mutation status were randomized (1:1) to PC/G (n = 118) or G (n = 118). EGFR mutation status was retrospectively determined for 76 patients, 52 (68.4%) of whom had EGFR-mutated tumors (exon 19 deletions in 26 and L858R point mutation in 24). OS was analyzed by the Kaplan-Meier method. The study was registered at ClinicalTrials.gov (NCT01017874).
  
  
  RESULTS
  Median OS was similar in the PC/G (26.9 months) and G (27.9 months) groups (hazard ratio = 0.94, 95% confidence interval: 0.68-1.31, p = 0.717). Median OS was longer with PC/G than with G in patients with EGFR wild-type tumors (28.4 versus 8.9 months) and longer with G than with PC/G in patients with EGFR-mutated tumors (45.7 versus 32.4 months), especially those with exon 19 deletions. Second-line postdiscontinuation therapy was common and included chemotherapy (PC/G, 41 of 118 [34.7%]; G, 73 of 118 [61.9%]) and rechallenge with an EGFR tyrosine kinase inhibitor (PC/G, 27 of 118 [22.9%]; G, 9 of 118 [7.6%]).
  
  
  CONCLUSIONS
  The progression-free survival and OS results from this study further demonstrate the importance of determining EGFR mutation status to select the most appropriate first-line treatment for patients with advanced NSCLC.
authors.affiliation: National Taiwan University Hospital, Taipei, Taiwan. Electronic address: chihyang@ntu.edu.tw.
authors.forename: James Chih-Hsin
authors.initials: JC
authors.lastname: Yang
authors.affiliation: Siriraj Hospital, Mahidol University, Bangkok, Thailand.
authors.forename: Vichien
authors.initials: V
authors.lastname: Srimuninnimit
authors.affiliation: Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors.forename: Myung-Ju
authors.initials: MJ
authors.lastname: Ahn
authors.affiliation: National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Chia-Chi
authors.initials: CC
authors.lastname: Lin
authors.affiliation: Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors.forename: Sang-We
authors.initials: SW
authors.lastname: Kim
authors.affiliation: Taipei Veterans General Hospital and National Yang-Ming University, Shi-Pai, Taipei, Taiwan.
authors.forename: Chun-Ming
authors.initials: CM
authors.lastname: Tsai
authors.affiliation: Prince of Wales Hospital, Sha Tin, Hong Kong.
authors.forename: Tony
authors.initials: T
authors.lastname: Mok
authors.affiliation: Eli Lilly Interamerica Inc., Buenos Aires, Argentina.
authors.forename: Mauro
authors.initials: M
authors.lastname: Orlando
authors.affiliation: Eli Lilly and Company, Gurgaon, Haryana, India.
authors.forename: Tarun
authors.initials: T
authors.lastname: Puri
authors.affiliation: Eli Lilly and Company, Shanghai, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.affiliation: Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors.forename: Keunchil
authors.initials: K
authors.lastname: Park
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D044466:Asian People / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D002945:Cisplatin / Q000008:administration & dosage; D005260:Female; D000077156:Gefitinib; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D000068437:Pemetrexed / Q000008:administration & dosage; D011799:Quinazolines / Q000008:administration & dosage
chemical_list: D011799:Quinazolines; D000068437:Pemetrexed; D002945:Cisplatin; D000077156:Gefitinib
keywords: East Asia; Gefitinib; Non–small cell lung cancer; Overall survival; Pemetrexed