PMID- 28007626
OWN - NLM
STAT- MEDLINE
DCOM- 20171116
LR  - 20181202
IS  - 1556-1380 (Electronic)
IS  - 1556-0864 (Linking)
VI  - 12
IP  - 4
DP  - 2017 Apr
TI  - Risk of Treatment-Related Toxicities from EGFR Tyrosine Kinase Inhibitors: A 
      Meta-analysis of Clinical Trials of Gefitinib, Erlotinib, and Afatinib in 
      Advanced EGFR-Mutated Non-Small Cell Lung Cancer.
PG  - 633-643
LID - S1556-0864(16)33582-1 [pii]
LID - 10.1016/j.jtho.2016.11.2236 [doi]
AB  - INTRODUCTION: Gefitinib, erlotinib, and afatinib are tyrosine kinase inhibitors 
      (TKIs) used for treatment of advanced EGFR-mutated NSCLC. Estimating differences 
      in toxicity between these EGFR TKIs is important for personalizing treatment. 
      METHODS: We performed a meta-analysis of randomized trials that compared EGFR TKI 
      therapy against chemotherapy or placebo. We extracted data from the EGFR TKI arm 
      for indirect comparisons to estimate the relative risk for toxic death, grade 3 
      to 4 (G3/4) adverse events (AEs), and discontinuation of treatment because of AE 
      for each EGFR TKI. RESULTS: Sixteen trials included 2535 patients with mutated or 
      wild-type EGFR. Toxic deaths were rare (1.7%), with pneumonitis being most 
      frequent cause and no significant differences between EGFR TKIs. Overall, 40% of 
      patients experienced G3/4 AEs. The risk for G3/4 AEs was lower with gefitinib 
      (29.1%) than with erlotinib (54.1%) or afatinib (42.1%) (p < 0.01). 
      Discontinuation of treatment because of AEs occurred in 7.7% of patients, with no 
      significant differences between EGFR TKIs. Diarrhea (in 53.3% of cases) and rash 
      (in 66.5%) were the most frequent AEs. The risk for rash was higher with afatinib 
      (84.8%) than with erlotinib (62.0%) or gefitinib (62.0%) (p < 0.01). The risk for 
      diarrhea was higher with afatinib (91.7%) than with erlotinib (42.4%) or 
      gefitinib (44.4%) (p < 0.01). The risk for increased liver enzyme levels was 
      higher with gefitinib (61.7%) than with erlotinib (17.8%) or afatinib (20.1%) (p 
      < 0.01). A risk-benefit contour was used to assess the trade-off between efficacy 
      and toxicity for different EGFR TKIs. CONCLUSIONS: EGFR TKIs are well tolerated, 
      with less than 10% of patients discontinuing treatment because of AEs. The 
      profile of and risk for toxicities vary between EGFR TKIs and can be used to 
      inform the selection of treatment.
CI  - Copyright (c) 2016 International Association for the Study of Lung Cancer. 
      Published by Elsevier Inc. All rights reserved.
FAU - Ding, Pei Ni
AU  - Ding PN
AD  - National Health and Medical Research Council Clinical Trials Centre, The 
      University of Sydney, Sydney, Australia; Department of Medical Oncology, 
      Liverpool Hospital, Sydney, Australia.
FAU - Lord, Sarah J
AU  - Lord SJ
AD  - National Health and Medical Research Council Clinical Trials Centre, The 
      University of Sydney, Sydney, Australia; School of Medicine, The University of 
      Notre Dame, Sydney, Australia.
FAU - Gebski, Val
AU  - Gebski V
AD  - National Health and Medical Research Council Clinical Trials Centre, The 
      University of Sydney, Sydney, Australia.
FAU - Links, Matthew
AU  - Links M
AD  - Cancer Care Centre, St. George Hospital, Sydney, Australia.
FAU - Bray, Victoria
AU  - Bray V
AD  - Department of Medical Oncology, Liverpool Hospital, Sydney, Australia.
FAU - Gralla, Richard J
AU  - Gralla RJ
AD  - Albert Einstein College of Medicine, Jacobi Medical Center, New York, New York.
FAU - Yang, James Chih-Hsin
AU  - Yang JC
AD  - Graduate Institute of Oncology, National Taiwan University and Department of 
      Oncology, National Taiwan University Hospital, Taipei, Republic of China.
FAU - Lee, Chee Khoon
AU  - Lee CK
AD  - National Health and Medical Research Council Clinical Trials Centre, The 
      University of Sydney, Sydney, Australia; Cancer Care Centre, St. George Hospital, 
      Sydney, Australia. Electronic address: chee.lee@ctc.usyd.edu.au.
LA  - eng
PT  - Journal Article
PT  - Meta-Analysis
DEP - 20161219
PL  - United States
TA  - J Thorac Oncol
JT  - Journal of thoracic oncology : official publication of the International 
      Association for the Study of Lung Cancer
JID - 101274235
RN  - 0 (Protein Kinase Inhibitors)
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 Combined Chemotherapy Protocols/*adverse effects
MH  - Carcinoma, Non-Small-Cell Lung/*drug therapy/pathology
MH  - Diarrhea/*chemically induced/diagnosis
MH  - ErbB Receptors/*antagonists & inhibitors/genetics
MH  - Erlotinib Hydrochloride/administration & dosage
MH  - Gefitinib
MH  - Humans
MH  - Lung Neoplasms/*drug therapy/pathology
MH  - Mutation
MH  - Neoplasm Staging
MH  - Prognosis
MH  - Protein Kinase Inhibitors/*adverse effects
MH  - Quinazolines/administration & dosage
MH  - Risk Factors
MH  - Survival Rate
OTO - NOTNLM
OT  - EGFR mutation
OT  - Meta-analysis
OT  - NSCLC
OT  - Tyrosine kinase inhibitors
EDAT- 2016/12/23 06:00
MHDA- 2017/11/29 06:00
CRDT- 2016/12/24 06:00
PHST- 2016/08/24 00:00 [received]
PHST- 2016/11/09 00:00 [revised]
PHST- 2016/11/24 00:00 [accepted]
PHST- 2016/12/23 06:00 [pubmed]
PHST- 2017/11/29 06:00 [medline]
PHST- 2016/12/24 06:00 [entrez]
AID - S1556-0864(16)33582-1 [pii]
AID - 10.1016/j.jtho.2016.11.2236 [doi]
PST - ppublish
SO  - J Thorac Oncol. 2017 Apr;12(4):633-643. doi: 10.1016/j.jtho.2016.11.2236. Epub 
      2016 Dec 19.