PMID- 25704957
OWN - NLM
STAT- MEDLINE
DCOM- 20151201
LR  - 20220317
IS  - 1872-8332 (Electronic)
IS  - 0169-5002 (Linking)
VI  - 88
IP  - 1
DP  - 2015 Apr
TI  - Pooled safety analysis of EGFR-TKI treatment for EGFR mutation-positive non-small 
      cell lung cancer.
PG  - 74-9
LID - S0169-5002(15)00091-4 [pii]
LID - 10.1016/j.lungcan.2015.01.026 [doi]
AB  - OBJECTIVES: Three epidermal growth factor receptor (EGFR) tyrosine kinase 
      inhibitors (TKIs) - afatinib, erlotinib, and gefitinib - are available for the 
      treatment of patients with EGFR mutation-positive non-small cell lung cancer 
      (NSCLC). Given the long-term exposure of such patients to EGFR-TKIs, the 
      toxicological properties of these agents in these individuals may differ from 
      those observed in unselected patients. We compared the frequencies of severe 
      adverse events (AEs) among EGFR mutation-positive NSCLC patients treated with 
      these three EGFR-TKIs. MATERIALS AND METHODS: We performed a pooled analysis of 
      severe AEs according to the type of EGFR-TKI administered with the use of data 
      extracted from prospective clinical trials that evaluated the clinical efficacy 
      of gefitinib, erlotinib, or afatinib in NSCLC patients with EGFR mutations. 
      RESULTS: Twenty-one trials published between 2006 and 2014 and including 1468 
      patients were eligible for analysis. Patients in 13 trials (n=457) received 
      gefitinib, those in 5 trials (n=513) received erlotinib, and those in 3 trials 
      (n=498) received afatinib. Rash and diarrhea of grade >/=3 were significantly more 
      frequent with afatinib therapy than with erlotinib or gefitinib therapy. The 
      frequency of interstitial lung disease (ILD) of grade >/=3 was low (0.6-2.2%) with 
      all three EGFR-TKIs and did not differ significantly among them. Gefitinib was 
      associated with a significantly higher frequency of hepatotoxicity of grade >/=3 
      compared with erlotinib or afatinib. The overall frequency of AEs leading to 
      treatment withdrawal was 6.1% (83 of 1354 evaluable patients), with such AEs 
      occurring significantly more often with afatinib or gefitinib than with 
      erlotinib. The most common withdrawal AEs were skin toxicity, ILD, and 
      hepatotoxicity. CONCLUSION: Such information on AEs should facilitate selection 
      of the most appropriate EGFR-TKI for EGFR mutation-positive NSCLC patients with 
      regard to mitigation of the risk for certain types of toxicity.
CI  - Copyright (c) 2015 Elsevier Ireland Ltd. All rights reserved.
FAU - Takeda, Masayuki
AU  - Takeda M
AD  - Department of Medical Oncology, Kinki University Faculty of Medicine, 377-2 
      Ohno-higashi, Osaka-Sayama 589-8511, Osaka, Japan.
FAU - Okamoto, Isamu
AU  - Okamoto I
AD  - Center for Clinical and Translational Research, Kyushu University Hospital, 3-1-1 
      Maidashi, Higashi-ku, Fukuoka 812-8582, Japan. Electronic address: 
      okamotoi@kokyu.med.kyushu-u.ac.jp.
FAU - Nakagawa, Kazuhiko
AU  - Nakagawa K
AD  - Department of Medical Oncology, Kinki University Faculty of Medicine, 377-2 
      Ohno-higashi, Osaka-Sayama 589-8511, Osaka, Japan.
LA  - eng
PT  - Journal Article
PT  - Meta-Analysis
PT  - Research Support, Non-U.S. Gov't
DEP - 20150207
PL  - Ireland
TA  - Lung Cancer
JT  - Lung cancer (Amsterdam, Netherlands)
JID - 8800805
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Quinazolines)
RN  - 41UD74L59M (Afatinib)
RN  - DA87705X9K (Erlotinib Hydrochloride)
RN  - EC 2.7.10.1 (EGFR protein, human)
RN  - EC 2.7.10.1 (ErbB Receptors)
RN  - S65743JHBS (Gefitinib)
SB  - IM
MH  - Afatinib
MH  - Antineoplastic Agents/*adverse effects/therapeutic use
MH  - Carcinoma, Non-Small-Cell Lung/*drug therapy/genetics/mortality
MH  - Chemical and Drug Induced Liver Injury/etiology
MH  - ErbB Receptors/*genetics
MH  - Erlotinib Hydrochloride/*adverse effects/therapeutic use
MH  - Gefitinib
MH  - Humans
MH  - Lung Neoplasms/*drug therapy/genetics/mortality
MH  - Mutation
MH  - Quinazolines/*adverse effects/therapeutic use
OTO - NOTNLM
OT  - Adverse event
OT  - Epidermal growth factor receptor
OT  - Non-small cell lung cancer
OT  - Tyrosine kinase inhibitor
OT  - ethnic difference
OT  - pooled analysis
EDAT- 2015/02/24 06:00
MHDA- 2015/12/15 06:00
CRDT- 2015/02/24 06:00
PHST- 2014/06/07 00:00 [received]
PHST- 2015/01/27 00:00 [revised]
PHST- 2015/01/30 00:00 [accepted]
PHST- 2015/02/24 06:00 [entrez]
PHST- 2015/02/24 06:00 [pubmed]
PHST- 2015/12/15 06:00 [medline]
AID - S0169-5002(15)00091-4 [pii]
AID - 10.1016/j.lungcan.2015.01.026 [doi]
PST - ppublish
SO  - Lung Cancer. 2015 Apr;88(1):74-9. doi: 10.1016/j.lungcan.2015.01.026. Epub 2015 
      Feb 7.