PMID- 23816963
OWN - NLM
STAT- MEDLINE
DCOM- 20140505
LR  - 20220309
IS  - 1527-7755 (Electronic)
IS  - 0732-183X (Linking)
VI  - 31
IP  - 27
DP  - 2013 Sep 20
TI  - LUX-Lung 4: a phase II trial of afatinib in patients with advanced non-small-cell 
      lung cancer who progressed during prior treatment with erlotinib, gefitinib, or 
      both.
PG  - 3335-41
LID - 10.1200/JCO.2012.45.0981 [doi]
AB  - PURPOSE: New molecular targeted agents are needed for patients with 
      non-small-cell lung cancer (NSCLC) who progress while receiving erlotinib, 
      gefitinib, or both. Afatinib, an oral irreversible ErbB family blocker, has 
      preclinical activity in epidermal growth factor receptor (EGFR [ErbB1]) mutant 
      models with EGFR-activating mutations, including T790M. PATIENTS AND METHODS: 
      This was a Japanese single-arm phase II trial conducted in patients with stage 
      IIIB to IV pulmonary adenocarcinoma who progressed after >/= 12 weeks of prior 
      erlotinib and/or gefitinib. Patients received afatinib 50 mg per day. The primary 
      end point was objective response rate (complete response or partial response) by 
      independent review. Secondary end points included progression-free survival 
      (PFS), overall survival (OS), and safety. RESULTS: Of 62 treated patients, 45 
      (72.6%) were EGFR mutation positive in their primary tumor according to local 
      and/or central laboratory analyses. Fifty-one patients (82.3%) fulfilled the 
      criteria of acquired resistance to erlotinib and/or gefitinib. Of 61 evaluable 
      patients, five (8.2%; 95% CI, 2.7% to 18.1%) had a confirmed objective response 
      rate (partial response). Median PFS was 4.4 months (95% CI, 2.8 to 4.6 months), 
      and median OS was 19.0 months (95% CI, 14.9 months to not achieved). Two patients 
      had acquired T790M mutations: L858R + T790M, and deletion in exon 19 + T790M; 
      they had stable disease for 9 months and 1 month, respectively. The most common 
      afatinib-related adverse events (AEs) were diarrhea (100%) and rash/acne (91.9%). 
      Treatment-related AEs leading to afatinib discontinuation were experienced by 18 
      patients (29%), of whom four also had progressive disease. CONCLUSION: Afatinib 
      demonstrated modest but noteworthy efficacy in patients with NSCLC who had 
      received third- or fourth-line treatment and who progressed while receiving 
      erlotinib and/or gefitinib, including those with acquired resistance to 
      erlotinib, gefitinib, or both.
FAU - Katakami, Nobuyuki
AU  - Katakami N
AD  - Nobuyuki Katakami, Kobe City Medical Center General Hospital, Kobe; Shinji Atagi, 
      National Hospital Organization Kinki-Chuo Chest Medical Center; Koji Takeda, 
      Osaka City General Hospital; Kazuto Nishio, Kinki University, Osaka; Koichi Goto, 
      National Cancer Center Hospital East, Chiba; Toyoaki Hida, Aichi Cancer Center 
      Hospital, Nagoya; Takeshi Horai, The Cancer Institute Hospital of Japanese 
      Foundation for Cancer Research, Tokyo; Akira Inoue, Tohoku University Hospital, 
      Sendai; Yukito Ichinose, National Kyushu Cancer Center, Fukuoka; Kunihiko 
      Koboyashi, Saitama International Medical Center, Saitama; Katsuyuki Kiura, 
      Okayama University, Okayama; Yoko Seki and Ryuichi Ebisawa, Nippon Boehringer 
      Ingelheim; Nobuyuki Yamamoto, Shizuoka Cancer Center, Shizuoka, Japan; and Mehdi 
      Shahidi, Boehringer Ingelheim, Bracknell, United Kingdom.
FAU - Atagi, Shinji
AU  - Atagi S
FAU - Goto, Koichi
AU  - Goto K
FAU - Hida, Toyoaki
AU  - Hida T
FAU - Horai, Takeshi
AU  - Horai T
FAU - Inoue, Akira
AU  - Inoue A
FAU - Ichinose, Yukito
AU  - Ichinose Y
FAU - Koboyashi, Kunihiko
AU  - Koboyashi K
FAU - Takeda, Koji
AU  - Takeda K
FAU - Kiura, Katsuyuki
AU  - Kiura K
FAU - Nishio, Kazuto
AU  - Nishio K
FAU - Seki, Yoko
AU  - Seki Y
FAU - Ebisawa, Ryuichi
AU  - Ebisawa R
FAU - Shahidi, Mehdi
AU  - Shahidi M
FAU - Yamamoto, Nobuyuki
AU  - Yamamoto N
LA  - eng
SI  - ClinicalTrials.gov/NCT00711594
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, Non-U.S. Gov't
DEP - 20130701
PL  - United States
TA  - J Clin Oncol
JT  - Journal of clinical oncology : official journal of the American Society of 
      Clinical Oncology
JID - 8309333
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Quinazolines)
RN  - 41UD74L59M (Afatinib)
RN  - DA87705X9K (Erlotinib Hydrochloride)
RN  - S65743JHBS (Gefitinib)
SB  - IM
CIN - J Clin Oncol. 2013 Sep 20;31(27):3303-6. PMID: 23980079
MH  - Adenocarcinoma/*drug therapy/genetics/pathology
MH  - Adenocarcinoma of Lung
MH  - Adult
MH  - Afatinib
MH  - Aged
MH  - Aged, 80 and over
MH  - Antineoplastic Agents/adverse effects/therapeutic use
MH  - Antineoplastic Combined Chemotherapy Protocols/adverse effects/therapeutic use
MH  - Disease Progression
MH  - Disease-Free Survival
MH  - Erlotinib Hydrochloride
MH  - Female
MH  - Gefitinib
MH  - Humans
MH  - Lung Neoplasms/*drug therapy/genetics/pathology
MH  - Male
MH  - Middle Aged
MH  - Quinazolines/adverse effects/*therapeutic use
EDAT- 2013/07/03 06:00
MHDA- 2014/05/06 06:00
CRDT- 2013/07/03 06:00
PHST- 2013/07/03 06:00 [entrez]
PHST- 2013/07/03 06:00 [pubmed]
PHST- 2014/05/06 06:00 [medline]
AID - JCO.2012.45.0981 [pii]
AID - 10.1200/JCO.2012.45.0981 [doi]
PST - ppublish
SO  - J Clin Oncol. 2013 Sep 20;31(27):3335-41. doi: 10.1200/JCO.2012.45.0981. Epub 
      2013 Jul 1.