PMID- 26105600 OWN - NLM STAT- MEDLINE DCOM- 20160609 LR - 20221207 IS - 1569-8041 (Electronic) IS - 0923-7534 (Linking) VI - 26 IP - 9 DP - 2015 Sep TI - 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. PG - 1883-1889 LID - S0923-7534(19)31770-3 [pii] LID - 10.1093/annonc/mdv270 [doi] AB - 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). PATIENTS AND 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. CONCLUSION: 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). CI - (c) The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com. FAU - Wu, Y-L AU - Wu YL AD - Guangdong Lung Cancer Institute, Guangdong General Hospital and Guangdong Academy of Medical Sciences, Guangzhou. Electronic address: syylwu@live.cn. FAU - Zhou, C AU - Zhou C AD - Department of Oncology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China. FAU - Liam, C-K AU - Liam CK AD - Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia. FAU - Wu, G AU - Wu G AD - Cancer Center of Union Hospital, Tongji Medical College, Huzhong University of Science and Technology, Wuhan. FAU - Liu, X AU - Liu X AD - Department of Internal Medicine Tumor, Academy of Military Medical Sciences Affiliated Hospital (307 Hospital of PLA), Beijing. FAU - Zhong, Z AU - Zhong Z AD - Cancer Centre, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing. FAU - Lu, S AU - Lu S AD - Department of Lung Cancer, Shanghai Chest Hospital, Shanghai. FAU - Cheng, Y AU - Cheng Y AD - Jilin Cancer Hospital, Changchun. FAU - Han, B AU - Han B AD - Department of Lung Cancer, Shanghai Chest Hospital, Shanghai. FAU - Chen, L AU - Chen L AD - Department of Medical Oncology, Cancer Hospital of Shantou University Medical College, Shantou. FAU - Huang, C AU - Huang C AD - Fujian Provincial Tumor Hospital, Fujian. FAU - Qin, S AU - Qin S AD - Nanjing Bayi Hospital, Nanjing. FAU - Zhu, Y AU - Zhu Y AD - Department of Lung Cancer, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing. FAU - Pan, H AU - Pan H AD - Department of Oncology, Sir Run Run Shaw Hospital Affiliated to Zhejiang University School of Medicine, Hangzhou. FAU - Liang, H AU - Liang H AD - Affiliated Xinan Hospital of Third Military Medical University, Chongqing. FAU - Li, E AU - Li E AD - First Affiliated Hospital, Medical School Xi'an Jiaotong University, Xi'an. FAU - Jiang, G AU - Jiang G AD - Cancer Hospital, Fudan University, Shanghai, China. FAU - How, S H AU - How SH AD - Department of Medicine, International Islamic University Malaysia, Kuala Lumpur, Malaysia. FAU - Fernando, M C L AU - Fernando MCL AD - Manila Doctors Hospital, Manila, The Philippines. FAU - Zhang, Y AU - Zhang Y AD - Roche (China) Holding Ltd, Shanghai, China. FAU - Xia, F AU - Xia F AD - Roche (China) Holding Ltd, Shanghai, China. FAU - Zuo, Y AU - Zuo Y AD - Roche (China) Holding Ltd, Shanghai, China. LA - eng SI - ClinicalTrials.gov/NCT01342965 PT - Clinical Trial, Phase III PT - Comparative Study PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20150623 PL - England TA - Ann Oncol JT - Annals of oncology : official journal of the European Society for Medical Oncology JID - 9007735 RN - 0 (Antineoplastic Agents) RN - 0 (Protein Kinase Inhibitors) RN - 0W860991D6 (Deoxycytidine) RN - BG3F62OND5 (Carboplatin) RN - DA87705X9K (Erlotinib Hydrochloride) RN - EC 2.7.10.1 (EGFR protein, human) RN - EC 2.7.10.1 (ErbB Receptors) RN - 0 (Gemcitabine) SB - IM MH - Adult MH - Aged MH - Antineoplastic Agents/therapeutic use MH - Antineoplastic Combined Chemotherapy Protocols/therapeutic use MH - Asian People MH - Carboplatin/adverse effects/*therapeutic use MH - Carcinoma, Non-Small-Cell Lung/*drug therapy/genetics/mortality MH - Deoxycytidine/adverse effects/*analogs & derivatives/therapeutic use MH - Disease-Free Survival MH - ErbB Receptors/antagonists & inhibitors/genetics MH - Erlotinib Hydrochloride/adverse effects/*therapeutic use MH - Female MH - Humans MH - Kaplan-Meier Estimate MH - Lung Neoplasms/*drug therapy/genetics/mortality MH - Male MH - Middle Aged MH - Protein Kinase Inhibitors/adverse effects/therapeutic use MH - Survival Analysis MH - Treatment Outcome MH - Gemcitabine OTO - NOTNLM OT - Asian OT - EGFR mutation-positive OT - NSCLC OT - erlotinib OT - first-line EDAT- 2015/06/25 06:00 MHDA- 2016/06/10 06:00 CRDT- 2015/06/25 06:00 PHST- 2015/02/20 00:00 [received] PHST- 2015/06/04 00:00 [accepted] PHST- 2015/06/25 06:00 [entrez] PHST- 2015/06/25 06:00 [pubmed] PHST- 2016/06/10 06:00 [medline] AID - S0923-7534(19)31770-3 [pii] AID - 10.1093/annonc/mdv270 [doi] PST - ppublish SO - Ann Oncol. 2015 Sep;26(9):1883-1889. doi: 10.1093/annonc/mdv270. Epub 2015 Jun 23.