title: Gefitinib or Erlotinib vs Chemotherapy for EGFR Mutation-Positive Lung Cancer: Individual Patient Data Meta-Analysis of Overall Survival.
abstract: We performed an individual patient data meta-analysis to examine the impact of first-generation epidermal growth factor receptor ( EGFR ) tyrosine kinase inhibitor (TKI) therapy on overall survival (OS) in advanced non-small cell lung cancer (NSCLC).
  
  
  
  Data from trials comparing EGFR-TKI against chemotherapy in exon 19 deletion (del19) or exon 21 L858R (L858R) EGFR mutations patients were used. We performed Cox regression to obtain hazard ratios (HRs) and 95% confidence intervals (CIs). Impact of postprogression therapies was examined in exploratory analyses. All statistical tests were two-sided.
  
  
  
  Six eligible trials (gefitinib = 3, erlotinib = 3) included 1231 patients; 632 received EGFR-TKI and 599 received chemotherapy. At a median 35.0 months follow-up, there were 780 deaths and 1004 progressions. There was no difference in OS between EGFR-TKI and chemotherapy (HR = 1.01, 95% CI = 0.88 to 1.17, P =  .84). There was also no difference in OS for Del19 (n = 682, HR = 0.96, 95% CI = 0.79 to 1.16, P =  .68) and L858R (n = 540, HR = 1.06, 95% CI = 0.86 to 1.32, P =  .59) subgroups ( P interaction = .47), or according to smoking status, sex, performance status, age, ethnicity, or histology. However, EGFR-TKI statistically significantly prolonged progression-free survival (PFS) overall (HR = 0.37, 95% CI = 0.32 to 0.42, P <  .001) and in all subgroups. Following progression, 73.8% from the chemotherapy arm received EGFR-TKI, and 65.9% from the EGFR-TKI arm received chemotherapy. Nine percent from the EGFR-TKI arm received no further treatment vs 0.6% from the chemotherapy arm. Following disease progression, patients randomly assigned to EGFR-TKI had shorter OS than those randomly assigned to chemotherapy (12.8 months, 95% CI = 11.4 to 14.3, vs 19.8 months, 95% CI = 17.6 to 21.7).
  
  
  
  Despite statistically significant PFS benefit, there is no relative OS advantage with frontline gefitinib or erlotinib vs chemotherapy in EGFR -mutated NSCLC. This finding is likely due to the high rate of crossover at progression.
authors.affiliation: NHMRC Clinical Trials Centre, The University of Sydney, Sydney, Australia.|Cancer Care Centre, St. George Hospital, Sydney, Australia.
authors.forename: Chee Khoon
authors.initials: CK
authors.lastname: Lee
authors.affiliation: NHMRC Clinical Trials Centre, The University of Sydney, Sydney, Australia.
authors.forename: Lucy
authors.initials: L
authors.lastname: Davies
authors.affiliation: Guangdong Lung Cancer Institute, Guangdong General Hospital and Guangdong Academy of Medical Sciences, Guangdong, China.
authors.forename: Yi-Long
authors.initials: YL
authors.lastname: Wu
authors.affiliation: Division of Thoracic Surgery, Department of Surgery, Kinki University Faculty of Medicine, Osaka-Sayama, Japan.|Hong Kong Cancer Institute, Department of Clinical Oncology, Chinese University of Hong Kong, Shatin, China.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Mitsudomi
authors.affiliation: Department of Palliative Medicine, Tohoku University School of Medicine, Sendai, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Inoue
authors.affiliation: Catalan Institute of Oncology, Germans Trias i Pujol Health Sciences Institute and Hospital, Barcelona, Spain.
authors.forename: Rafael
authors.initials: R
authors.lastname: Rosell
authors.affiliation: Department of Oncology, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China.
authors.forename: Caicun
authors.initials: C
authors.lastname: Zhou
authors.affiliation: Department of Medical Oncology, Kinki University Faculty of Medicine, Osaka-Sayama, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Nakagawa
authors.affiliation: Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.
authors.forename: Sumitra
authors.initials: S
authors.lastname: Thongprasert
authors.affiliation: Department of Medical Oncology, Kinki University Faculty of Medicine, Osaka-Sayama, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Fukuoka
authors.affiliation: NHMRC Clinical Trials Centre, The University of Sydney, Sydney, Australia.|School of Medicine, The University of Norte Dame, Sydney, Australia.
authors.forename: Sally
authors.initials: S
authors.lastname: Lord
authors.affiliation: NHMRC Clinical Trials Centre, The University of Sydney, Sydney, Australia.|Department of Statistics, Macquarie University, Sydney, Australia.
authors.forename: Ian
authors.initials: I
authors.lastname: Marschner
authors.affiliation: Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taiwan.
authors.forename: Yu-Kang
authors.initials: YK
authors.lastname: Tu
authors.affiliation: Albert Einstein College of Medicine, Jacobi Medical Center, NY, USA.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Gralla
authors.affiliation: NHMRC Clinical Trials Centre, The University of Sydney, Sydney, Australia.
authors.forename: Val
authors.initials: V
authors.lastname: Gebski
authors.affiliation: Hong Kong Cancer Institute, Department of Clinical Oncology, Chinese University of Hong Kong, Shatin, China.
authors.forename: Tony
authors.initials: T
authors.lastname: Mok
authors.affiliation: Department of Oncology, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: James Chih-Hsin
authors.initials: JC
authors.lastname: Yang
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001483:Base Sequence; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D018450:Disease Progression; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000235:genetics*; D000069347:Erlotinib Hydrochloride / Q000627:therapeutic use*; D005091:Exons; D005500:Follow-Up Studies; D000077156:Gefitinib; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011799:Quinazolines / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D019233:Retreatment; D017384:Sequence Deletion
chemical_list: D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D000069347:Erlotinib Hydrochloride; D066246:ErbB Receptors; D000077156:Gefitinib