PMID- 29653820
OWN - NLM
STAT- MEDLINE
DCOM- 20190307
LR  - 20221207
IS  - 1938-0690 (Electronic)
IS  - 1525-7304 (Linking)
VI  - 19
IP  - 4
DP  - 2018 Jul
TI  - Afatinib as First-line Treatment of Older Patients With EGFR Mutation-Positive 
      Non-Small-Cell Lung Cancer: Subgroup Analyses of the LUX-Lung 3, LUX-Lung 6, and 
      LUX-Lung 7 Trials.
PG  - e465-e479
LID - S1525-7304(18)30051-2 [pii]
LID - 10.1016/j.cllc.2018.03.009 [doi]
AB  - BACKGROUND: Afatinib is approved in the US, Europe, and several other regions for 
      first-line treatment for epidermal growth factor receptor mutation-positive 
      (EGFRm(+)) non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: 
      Treatment-naive patients with advanced EGFRm(+) NSCLC were randomized to afatinib 
      (40 mg/d) versus cisplatin/pemetrexed (LUX-Lung 3 [LL3]) or cisplatin/gemcitabine 
      (LUX-Lung 6 [LL6]), or versus gefitinib (250 mg/d; LUX-Lung 7 [LL7]). We report 
      subgroup analyses according to age, including 65 years or older versus younger 
      than 65 years (preplanned; LL3/LL6) and additional cutoffs up to 75 years and 
      older (exploratory; LL7). Progression-free survival (PFS), overall survival (OS), 
      and adverse events (AEs) were evaluated. RESULTS: Among the 134 of 345 (39%) and 
      86 of 364 (24%) patients aged 65 years and older in LL3 and LL6, median PFS was 
      improved with afatinib versus chemotherapy (LL3: hazard ratio [HR], 0.64 [95% 
      confidence interval (CI), 0.39-1.03]; LL6: HR, 0.16 [95% CI, 0.07-0.39]). 
      Afatinib significantly improved OS versus chemotherapy in elderly patients with 
      Del19(+) NSCLC in LL3 (HR, 0.39 [95% CI, 0.19-0.80]). Among the 40 of 319 
      patients (13%) aged 75 years or older in LL7, median PFS (HR, 0.69 [95% CI, 
      0.33-1.44]) favored afatinib, consistent with the overall population. 
      Afatinib-associated AEs in older patients were consistent with the overall 
      populations. CONCLUSIONS: Subgroup analyses of the LL3, LL6, and LL7 trials show 
      that afatinib is an effective and tolerable treatment for patients with EGFRm(+) 
      NSCLC, independent of age.
CI  - Copyright (c) 2018 The Authors. Published by Elsevier Inc. All rights reserved.
FAU - Wu, Yi-Long
AU  - Wu YL
AD  - Guangdong Lung Cancer Institute, Guangdong General Hospital and Guangdong Academy 
      of Medical Sciences, Guangzhou, China. Electronic address: syylwu@live.cn.
FAU - Sequist, Lecia V
AU  - Sequist LV
AD  - Department of Thoracic Oncology, Massachusetts General Hospital and Harvard 
      Medical School, Boston, MA.
FAU - Tan, Eng-Huat
AU  - Tan EH
AD  - Division of Medical Oncology, National Cancer Centre, Singapore, Singapore.
FAU - Geater, Sarayut L
AU  - Geater SL
AD  - Department of Internal Medicine, Prince of Songkla University, Songkhla, 
      Thailand.
FAU - Orlov, Sergey
AU  - Orlov S
AD  - Department of Thoracic Oncology, Pavlov State Medical University, St Petersburg, 
      Russia.
FAU - Zhang, Li
AU  - Zhang L
AD  - Department of Medical Oncology, State Key Laboratory of Oncology in South China, 
      Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University 
      Cancer Center, Guangzhou, China.
FAU - Lee, Ki Hyeong
AU  - Lee KH
AD  - Department of Internal Medicine, Chungbuk National University Hospital, Cheongju, 
      South Korea.
FAU - Tsai, Chun-Ming
AU  - Tsai CM
AD  - Department of Oncology, Taipei Veterans General Hospital, Taipei, Taiwan.
FAU - Kato, Terufumi
AU  - Kato T
AD  - Department of Respiratory Medicine, Kanagawa Cardiovascular and Respiratory 
      Center, Yokohama, Japan.
FAU - Barrios, Carlos H
AU  - Barrios CH
AD  - Department of Internal Medicine, PUCRS School of Medicine, Porto Alegre, Rio 
      Grande do Sul, Brazil.
FAU - Schuler, Martin
AU  - Schuler M
AD  - Department of Medical Oncology, West German Cancer Center, University Hospital 
      Essen, University Duisburg-Essen, Essen, Germany.
FAU - Hirsh, Vera
AU  - Hirsh V
AD  - Faculty of Medicine/Oncology, McGill University, Montreal, Quebec, Canada.
FAU - Yamamoto, Nobuyuki
AU  - Yamamoto N
AD  - Wakayama Medical University, Wakayama, Wakayama Prefecture, Japan.
FAU - O'Byrne, Kenneth
AU  - O'Byrne K
AD  - Department of Medical Oncology, Princess Alexandra Hospital and Queensland 
      University of Technology, Brisbane, Queensland, Australia.
FAU - Boyer, Michael
AU  - Boyer M
AD  - Chris O'Brien Lifehouse, Camperdown, New South Wales, Australia.
FAU - Mok, Tony
AU  - Mok T
AD  - Department of Clinical Oncology, State Key Laboratory of South China, Hong Kong 
      Cancer Institute, The Chinese University of Hong Kong, Prince of Wales Hospital, 
      Shatin, New Territories, Hong Kong, China.
FAU - Peil, Barbara
AU  - Peil B
AD  - Boehringer Ingelheim Pharma GmbH & Co KG, Ingelheim am Rhein, Germany.
FAU - Marten, Angela
AU  - Marten A
AD  - Boehringer Ingelheim Pharma GmbH & Co KG, Ingelheim am Rhein, Germany.
FAU - Chih-Hsin Yang, James
AU  - Chih-Hsin Yang J
AD  - Department of Oncology, National Taiwan University Hospital and National Taiwan 
      University, Taipei, Taiwan.
FAU - Paz-Ares, Luis
AU  - Paz-Ares L
AD  - Department of Lung Cancer, Hospital Universitario Doce de Octubre, Universidad 
      Complutense, CiberOnc and CNIO, Madrid, Spain.
FAU - Park, Keunchil
AU  - Park K
AD  - Division of Hematology/Oncology, Samsung Medical Center, Sungkyunkwan University 
      School of Medicine, Seoul, Korea.
LA  - eng
SI  - ClinicalTrials.gov/NCT00949650
SI  - ClinicalTrials.gov/NCT01121393
SI  - ClinicalTrials.gov/NCT01466660
PT  - Clinical Trial, Phase II
PT  - Clinical Trial, Phase III
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20180317
PL  - United States
TA  - Clin Lung Cancer
JT  - Clinical lung cancer
JID - 100893225
RN  - 0 (Antineoplastic Agents)
RN  - 04Q9AIZ7NO (Pemetrexed)
RN  - 0W860991D6 (Deoxycytidine)
RN  - 41UD74L59M (Afatinib)
RN  - EC 2.7.10.1 (EGFR protein, human)
RN  - EC 2.7.10.1 (ErbB Receptors)
RN  - Q20Q21Q62J (Cisplatin)
RN  - S65743JHBS (Gefitinib)
RN  - 0 (Gemcitabine)
SB  - IM
MH  - Adult
MH  - Afatinib/*therapeutic use
MH  - Aged
MH  - Antineoplastic Agents/*therapeutic use
MH  - Carcinoma, Non-Small-Cell Lung/*drug therapy/genetics/mortality
MH  - Cisplatin/therapeutic use
MH  - Deoxycytidine/analogs & derivatives/therapeutic use
MH  - ErbB Receptors/genetics
MH  - Female
MH  - Gefitinib/therapeutic use
MH  - Humans
MH  - Lung Neoplasms/*drug therapy/genetics/mortality
MH  - Male
MH  - Middle Aged
MH  - Mutation
MH  - Pemetrexed/therapeutic use
MH  - Progression-Free Survival
MH  - Gemcitabine
OTO - NOTNLM
OT  - EGFR blocker
OT  - Elderly
OT  - Gefitinib
OT  - NSCLC
OT  - Tyrosine kinase inhibitor
EDAT- 2018/04/15 06:00
MHDA- 2019/03/08 06:00
CRDT- 2018/04/15 06:00
PHST- 2017/11/08 00:00 [received]
PHST- 2018/02/20 00:00 [revised]
PHST- 2018/03/10 00:00 [accepted]
PHST- 2018/04/15 06:00 [pubmed]
PHST- 2019/03/08 06:00 [medline]
PHST- 2018/04/15 06:00 [entrez]
AID - S1525-7304(18)30051-2 [pii]
AID - 10.1016/j.cllc.2018.03.009 [doi]
PST - ppublish
SO  - Clin Lung Cancer. 2018 Jul;19(4):e465-e479. doi: 10.1016/j.cllc.2018.03.009. Epub 
      2018 Mar 17.