title: Final overall survival results from a randomised, phase III study of erlotinib versus chemotherapy as first-line treatment of EGFR mutation-positive advanced non-small-cell lung cancer (OPTIMAL, CTONG-0802).
abstract: BACKGROUND
  The OPTIMAL study was the first study to compare efficacy and tolerability of the epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) erlotinib, versus standard chemotherapy in first-line treatment of patients with EGFR mutation-positive advanced non-small-cell lung cancer (NSCLC). Findings from final overall survival (OS) analysis and assessment of post-study treatment impact are presented.
  
  
  METHODS
  Of 165 randomised patients, 82 received erlotinib and 72 gemcitabine plus carboplatin. Final OS analyses were conducted when 70% of deaths had occurred in the intent-to-treat population. Subgroup OS was analysed by Cox proportional hazards model and included randomisation stratification factors and post-study treatments.
  
  
  RESULTS
  Median OS was similar between the erlotinib (22.8 months) and chemotherapy (27.2 months) arms with no significant between-group differences in the overall population [hazard ratio (HR), 1.19; 95% confidence interval (CI) 0.83-1.71; P = 0.2663], the exon 19 deletion subpopulation (HR, 1.52; 95% CI 0.91-2.52; P = 0.1037) or the exon 21 L858 mutation subpopulation (HR, 0.92; 95% CI 0.55-1.54; P = 0.7392). More patients in the erlotinib arm versus the chemotherapy arm did not receive any post-study treatment (36.6% versus 22.2%). Patients who received sequential combination of EGFR-TKI and chemotherapy had significantly improved OS compared with those who received EGFR-TKI or chemotherapy only (29.7 versus 20.7 or 11.2 months, respectively; P < 0.0001). OS was significantly shorter in patients who did not receive post-study treatments compared with those who received subsequent treatments in both arms.
  
  
  CONCLUSIONS
  The significant OS benefit observed in patients treated with EGFR-TKI emphasises its contribution to improving survival of EGFR mutant NSCLC patients, suggesting that erlotinib should be considered standard first-line treatment of EGFR mutant patients and EGFR-TKI treatment following first-line therapy also brings significant benefits to those patients.
  
  
  BACKGROUND
  NCT00874419.
authors.affiliation: Department of Oncology, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai. Electronic address: caicunzhoudr@163.com.
authors.forename: C
authors.initials: C
authors.lastname: Zhou
authors.affiliation: Guangdong Lung Cancer Institute, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou.
authors.forename: Y L
authors.initials: YL
authors.lastname: Wu
authors.affiliation: Department of Tumour Medicine, Cancer Hospital of Harbin Medical University, Harbin.
authors.forename: G
authors.initials: G
authors.lastname: Chen
authors.affiliation: Department of Medical Oncology, Jiangsu Province Cancer Hospital, Nanjing.
authors.forename: J
authors.initials: J
authors.lastname: Feng
authors.affiliation: Department of Pulmonary Oncology, 307 Hospital of the Academy of Military Medical Sciences, Cancer Center, Beijing.
authors.forename: X-Q
authors.initials: XQ
authors.lastname: Liu
authors.affiliation: Department of Medical Oncology, Tianjin Cancer Hospital, Tianjin.
authors.forename: C
authors.initials: C
authors.lastname: Wang
authors.affiliation: Beijing Chest Hospital, Capital Medical University, Beijing.
authors.forename: S
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Peking University School of Oncology, Beijing Cancer Hospital, Beijing.
authors.forename: J
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Oncology, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai.
authors.forename: S
authors.initials: S
authors.lastname: Zhou
authors.affiliation: Department of Oncology, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai.
authors.forename: S
authors.initials: S
authors.lastname: Ren
authors.affiliation: Shanghai Chest Hospital, Affiliated to Shanghai Jiao Tong University, Shanghai.
authors.forename: S
authors.initials: S
authors.lastname: Lu
authors.affiliation: Sun Yat-sen University Cancer Center, Guangzhou.
authors.forename: L
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Xiangya Hospital, Central South University, Changsha.
authors.forename: C
authors.initials: C
authors.lastname: Hu
authors.affiliation: Second Xiangya Hospital, Central South University, Changsha.
authors.forename: C
authors.initials: C
authors.lastname: Hu
authors.affiliation: Hunan Province Cancer Hospital, Changsha.
authors.forename: Y
authors.initials: Y
authors.lastname: Luo
authors.affiliation: Cancer Hospital of Shantou University Medical College, Shantou.
authors.forename: L
authors.initials: L
authors.lastname: Chen
authors.affiliation: Renji Hospital, Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai.
authors.forename: M
authors.initials: M
authors.lastname: Ye
authors.affiliation: The First Affiliated Hospital of Suzhou University, Suzhou.
authors.forename: J
authors.initials: J
authors.lastname: Huang
authors.affiliation: Department of Thoracic Surgery, Xuanwu Hospital of Capital Medical University, Beijing.
authors.forename: X
authors.initials: X
authors.lastname: Zhi
authors.affiliation: Zhejiang Cancer Hospital, Hangzhou.
authors.forename: Y
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Changzheng Hospital, The Second Military Medical University, Shanghai.
authors.forename: Q
authors.initials: Q
authors.lastname: Xiu
authors.affiliation: Harbin Institute of Hematology and Oncology, Harbin.
authors.forename: J
authors.initials: J
authors.lastname: Ma
authors.affiliation: Peking Union Medical College Hospital, Beijing.
authors.forename: L
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: C
authors.initials: C
authors.lastname: You
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D016190:Carboplatin / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics; D000069347:Erlotinib Hydrochloride / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D008297:Male; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D016019:Survival Analysis; D016896:Treatment Outcome; D000093542:Gemcitabine
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D003841:Deoxycytidine; D016190:Carboplatin; D000069347:Erlotinib Hydrochloride; C512478:EGFR protein, human; D066246:ErbB Receptors; D000093542:Gemcitabine
keywords: EGFR mutations; chemotherapy; erlotinib; non-small-cell lung cancer; overall survival