title: First-line erlotinib versus gemcitabine/cisplatin in patients with advanced EGFR mutation-positive non-small-cell lung cancer: analyses from the phase III, randomized, open-label, ENSURE study.
abstract: BACKGROUND
  The phase III, randomized, open-label ENSURE study (NCT01342965) evaluated first-line erlotinib versus gemcitabine/cisplatin (GP) in patients from China, Malaysia and the Philippines with epidermal growth factor receptor (EGFR) mutation-positive non-small-cell lung cancer (NSCLC).
  
  
  METHODS
  Patients ≥18 years old with histologically/cytologically confirmed stage IIIB/IV EGFR mutation-positive NSCLC and Eastern Cooperative Oncology Group performance status 0-2 were randomized 1:1 to receive erlotinib (oral; 150 mg once daily until progression/unacceptable toxicity) or GP [G 1250 mg/m(2) i.v. days 1 and 8 (3-weekly cycle); P 75 mg/m(2) i.v. day 1, (3-weekly cycle) for up to four cycles]. Primary end point: investigator-assessed progression-free survival (PFS). Other end points include objective response rate (ORR), overall survival (OS), and safety.
  
  
  RESULTS
  A total of 217 patients were randomized: 110 to erlotinib and 107 to GP. Investigator-assessed median PFS was 11.0 months versus 5.5 months, erlotinib versus GP, respectively [hazard ratio (HR), 0.34, 95% confidence interval (CI) 0.22-0.51; log-rank P < 0.0001]. Independent Review Committee-assessed median PFS was consistent (HR, 0.42). Median OS was 26.3 versus 25.5 months, erlotinib versus GP, respectively (HR, 0.91, 95% CI 0.63-1.31; log-rank P = .607). ORR was 62.7% for erlotinib and 33.6% for GP. Treatment-related serious adverse events (AEs) occurred in 2.7% versus 10.6% of erlotinib and GP patients, respectively. The most common grade ≥3 AEs were rash (6.4%) with erlotinib, and neutropenia (25.0%), leukopenia (14.4%), and anemia (12.5%) with GP.
  
  
  CONCLUSIONS
  These analyses demonstrate that first-line erlotinib provides a statistically significant improvement in PFS versus GP in Asian patients with EGFR mutation-positive NSCLC (NCT01342965).
authors.affiliation: Guangdong Lung Cancer Institute, Guangdong General Hospital and Guangdong Academy of Medical Sciences, Guangzhou. Electronic address: syylwu@live.cn.
authors.forename: Y-L
authors.initials: YL
authors.lastname: Wu
authors.affiliation: Department of Oncology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: C
authors.initials: C
authors.lastname: Zhou
authors.affiliation: Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: C-K
authors.initials: CK
authors.lastname: Liam
authors.affiliation: Cancer Center of Union Hospital, Tongji Medical College, Huzhong University of Science and Technology, Wuhan.
authors.forename: G
authors.initials: G
authors.lastname: Wu
authors.affiliation: Department of Internal Medicine Tumor, Academy of Military Medical Sciences Affiliated Hospital (307 Hospital of PLA), Beijing.
authors.forename: X
authors.initials: X
authors.lastname: Liu
authors.affiliation: Cancer Centre, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing.
authors.forename: Z
authors.initials: Z
authors.lastname: Zhong
authors.affiliation: Department of Lung Cancer, Shanghai Chest Hospital, Shanghai.
authors.forename: S
authors.initials: S
authors.lastname: Lu
authors.affiliation: Jilin Cancer Hospital, Changchun.
authors.forename: Y
authors.initials: Y
authors.lastname: Cheng
authors.affiliation: Department of Lung Cancer, Shanghai Chest Hospital, Shanghai.
authors.forename: B
authors.initials: B
authors.lastname: Han
authors.affiliation: Department of Medical Oncology, Cancer Hospital of Shantou University Medical College, Shantou.
authors.forename: L
authors.initials: L
authors.lastname: Chen
authors.affiliation: Fujian Provincial Tumor Hospital, Fujian.
authors.forename: C
authors.initials: C
authors.lastname: Huang
authors.affiliation: Nanjing Bayi Hospital, Nanjing.
authors.forename: S
authors.initials: S
authors.lastname: Qin
authors.affiliation: Department of Lung Cancer, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing.
authors.forename: Y
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Department of Oncology, Sir Run Run Shaw Hospital Affiliated to Zhejiang University School of Medicine, Hangzhou.
authors.forename: H
authors.initials: H
authors.lastname: Pan
authors.affiliation: Affiliated Xinan Hospital of Third Military Medical University, Chongqing.
authors.forename: H
authors.initials: H
authors.lastname: Liang
authors.affiliation: First Affiliated Hospital, Medical School Xi'an Jiaotong University, Xi'an.
authors.forename: E
authors.initials: E
authors.lastname: Li
authors.affiliation: Cancer Hospital, Fudan University, Shanghai, China.
authors.forename: G
authors.initials: G
authors.lastname: Jiang
authors.affiliation: Department of Medicine, International Islamic University Malaysia, Kuala Lumpur, Malaysia.
authors.forename: S H
authors.initials: SH
authors.lastname: How
authors.affiliation: Manila Doctors Hospital, Manila, The Philippines.
authors.forename: M C L
authors.initials: MCL
authors.lastname: Fernando
authors.affiliation: Roche (China) Holding Ltd, Shanghai, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Roche (China) Holding Ltd, Shanghai, China.
authors.forename: F
authors.initials: F
authors.lastname: Xia
authors.affiliation: Roche (China) Holding Ltd, Shanghai, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Zuo
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D044466:Asian People; D016190:Carboplatin / Q000009:adverse effects / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D003841:Deoxycytidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics; D000069347:Erlotinib Hydrochloride / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D008297:Male; D008875:Middle Aged; 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: Asian; EGFR mutation-positive; NSCLC; erlotinib; first-line